****** 8256988
----K I
----T Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss.
----A OBJECTIVE: To determine whether augmentation of dietary calcium is effective in the prevention of early postmenopausal bone loss. DESIGN: Three-arm, placebo-controlled, randomized parallel trial. The study duration was 2.9 +/- 1.1 (SD) years. SETTING: General community. PARTICIPANTS: 118 healthy, white women 3 to 6 years after spontaneous menopause, recruited by community announcement. INTERVENTIONS: Random allocation to daily intake of 1700 mg of calcium (calcium carbonate given in divided doses with meals); placebo; or conjugated equine estrogens (0.625 mg; days 1 to 25), progesterone (10 mg; days 16 to 25), and 1700 mg of elemental calcium daily. Each participant  received 400 IU of vitamin D daily. MAIN OUTCOME MEASURES: Total body calcium measured by delayed gamma neutron activation  analysis and whole-body counting; bone mineral density of the spine, femur, and radius measured by photon absorptiometry. RESULTS: Bone mineral density declined in the placebo group for the lumbar spine (-2.1%/y; 95% Cl, -3.3 to -0.9), femoral neck (-2.0%/y; Cl, -2.6 to -1.2), trochanter (-1.6%/y; Cl, -2.4 to -0.8), Ward triangle (-2.7%/y; Cl, -3.7 to -1.7), and total body calcium (-2.0%/y; Cl, -2.2 to -1.8). Rates of change were intermediate for calcium augmentation compared with placebo and estrogen-progesterone-calcium but statistically significant compared with placebo for total body calcium (-0.5%/y; Cl, -0.9 to -0.1; P = 0.006) and the femoral neck (-0.8%/y; Cl, -1.4 to -0.2; P = 0.03). CONCLUSIONS: Although less effective than estrogen-progesterone-calcium, calcium augmentation alone significantly retards bone loss from the femoral neck and improves calcium balance in recently postmenopausal women. Dietary calcium augmentation should be recommended as a strategic option in helping to prevent early postmenopausal bone loss.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Analysis_of_Variance_MeSH M_Bone_Density_MeSH M_Calcium_Carbonate_MeSH S_analysis_MeSH Calcium_Carbonate_analysis_MeSH S_therapeutic_use_MeSH Calcium_Carbonate_therapeutic_use_MeSH M_Calcium__Dietary_MeSH S_analysis_MeSH Calcium__Dietary_analysis_MeSH S_therapeutic_use_MeSH Calcium__Dietary_therapeutic_use_MeSH M_Combined_Modality_Therapy_MeSH M_Comparative_Study_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_metabolism_MeSH Osteoporosis__Postmenopausal_metabolism_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 8259754
----K I
----T Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women.
----A Two hundred and forty-two postmenopausal women between 45 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and randomly allocated to treatment either with transdermal estradiol therapy (Estraderm 50 micrograms/24h) (E) or placebo (P). The patches were changed twice a week and treatment continued for 12 weeks. No progestogen supplement therapy was given during the study. No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than six months ago. As a part of a larger study assessing women's quality of life, a Swedish version of 'McCoy's Sex Scale Questionnaire' was administered at the start of treatment and after 12 weeks. This questionnaire contains nine items regarding different aspects of sexual life. The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared. Items regarding 'satisfaction with frequency of sexual activity, sexual fantasies, degree of enjoyment, vaginal lubrication and pain during intercourse' were positively influenced in the E group compared to the P group. Items not affected were 'frequency of orgasm and sexual arousal'. A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life questionnaires.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Questionnaires_MeSH P_Sexual_Behavior_MeSH 
****** 8272307
----K I
----T Postmenopausal hormone use and cholecystectomy in a large prospective study.
----A OBJECTIVE: To examine the association between postmenopausal hormone use and cholecystectomy. METHODS: A prospective cohort study was performed, with follow-up every 2 years. Participants were 54,845 postmenopausal United States nurses, who reported both hormone use and cholecystectomy on mailed questionnaires. RESULTS: Cholecystectomy was reported by 1750 women during 8 years of follow-up. After adjusting for confounding factors, women currently using postmenopausal hormones were at an increased risk of cholecystectomy (relative risk [RR] 2.1, 95% confidence interval [CI] 1.9-2.4) compared to never-users. For current users, the risk of cholecystectomy increased with increasing duration of hormone use (RR 2.6, 95% CI 2.2-3.1 for 10 years or more) and higher doses of estrogen (RR 2.4, 95% CI 2.0-2.9 for users of 1.25 mg or more). Although the risk for past hormone users decreased substantially in women who had discontinued use 1-2.9 years ago (RR 1.6, 95% CI 1.2-2.0), a small risk persisted for women who had stopped taking hormones 5 or more years previously (RR 1.3, 95% CI 1.1-1.6). However, after controlling for time since last use, duration of past use had little or no effect on the risk of cholecystectomy (RR 1.4 and RR 1.7 for past users of less than 2 years and 10 or more years' duration, respectively). CONCLUSION: Women using postmenopausal hormones are at an increased risk of cholecystectomy. Women and their physicians should consider the spectrum of risks and benefits when deciding whether to take hormones.
----P Journal_Article 
----M M_Cholecystectomy_MeSH S_statistics_&_numerical_data_MeSH Cholecystectomy_statistics_&_numerical_data_MeSH M_Cholelithiasis_MeSH S_etiology_MeSH Cholelithiasis_etiology_MeSH S_surgery_MeSH Cholelithiasis_surgery_MeSH M_Cohort_Studies_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Risk_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 8198628
----K I
----T Nylestriol replacement therapy in postmenopausal women. A three-year prospective study.
----A A three-year prospective study was carried out in 283 postmenopausal women to evaluate the effects of a long-acting estriol derivative-nylestriol. The women were randomly assigned into 3 groups: group A (136 cases, nylestriol 2 mg/2 wk), group B (97, nylestriol 1 mg/2 wk) and group C (50, placebo/2wk). LDL-C decreased and HDL-C increased after 3 months of medication (P < 0.05), but TC and TG not significantly changed in any group (P > 0.05). No changes of lipids were found in group C (P > 0.05). Serum ALP, Ca/Cr and Hpr/Cr in fasting urine decreased in 3 months in both group A and B (P < 0.05), but not in group C (P > 0.05). Forearm bone mineral content loss was restrained in groups A and B (P > 0.05), but decreased markedly in group C (P < 0.01). The Kupperman index scores decreased by about 50% after 3 months and 80% in 12 months in groups A and B. Nylestriol induced mild stimulatory effect on the uterine endometrium, and addition of 6 mg of provera daily for 7-10 days every 6 months is recommended. Nylestriol exhibited no obvious effect on the breast. This study demonstrated that nylestriol can be used as an effective and acceptable estrogen replacement therapy for postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Quinestrol_MeSH S_analogs_&_derivatives_MeSH Quinestrol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Quinestrol_therapeutic_use_MeSH 
****** 7968643
----K E
----T Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study.
----A The effects of oral micronized progesterone on the endometrium and bleeding pattern have been assessed in a multicenter study of 101 postmenopausal patients. During a minimum of 6 cycles, the participants received either percutaneous 17 beta-estradiol (1.5 mg/day) associated with micronized progesterone (100 mg/day), given at bedtime for 21/28 days or 25 days/calendar month (n = 98) [1], or E2 (3 mg/day) for 25 days associated with progesterone (300 mg/day), from day 16 to day 25 (n = 3) [2], according to their willingness to induce, or not, cyclic withdrawal bleeding. Each endometrial biopsy performed at 6-month minimum was assessed by two independent pathologists: results showed 61% quiescent without mitosis, 23% mildly active with very rare mitoses and 8% partial secretory endometrium. The remaining biopsies showed inadequate tissue (4%) or a sub-atrophy (4%). No hyperplasia was found by any pathologist. In the case of inadequate material, the mean thickness of endometrial mucosa measured by ultrasonography was 3.9 mm. Amenorrhea incidence was 93.3 and 91.6% at the 3rd and 6th month of therapy, respectively. No bleeding occurred in more than 80% of women. The results show that a low dose of oral progesterone (100 mg/day), given during 25 days, efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in the majority of postmenopausal women, allowing better compliance to long-term therapy.
----P Clinical_Trial Journal_Article Multicenter_Study 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Aged_MeSH P_Amenorrhea_MeSH M_Endometrium_MeSH S_cytology_MeSH Endometrium_cytology_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Patient_Compliance_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH 
****** 7569150
----K I
----T [Double-blind method of the effect of menopause symptoms, lipid profile, and endometrial thickness of continuous therapy with estradiol valerate and medroxyprogesterone acetate]
----A Continuous combined therapy (CCT) using estrogens and progestagens has appeared as an alternative to avoid vaginal bleeding, which is characteristic of sequential hormone therapy, and the main reason for the stopping treatment. Irregular vaginal bleeding can occur at the beginning of treatment, but it has been observed that after a few months patients are in amenorrhea. Fifty postmenopausal women were studied in order to evaluate the clinical outcome. Half of them were treated with a product containing 2 mg estradiol valerate and 2.5 mg medroxiprogesterone acetate, while the other half received a placebo. Menopause symptomatology was recorded as described by Blatt-Kupperman, depression was evaluated with the use of Hamilton's test, lipid profile by enzymatic methods and endometrial thickness by transvaginal ultrasonography. Patients were evaluated at the beginning, third and sixth month of the study, following a double blind methodology. Symptomatology diminished both in patients under CCT and using placebo, although improvement was significantly greater in patient under CCT. Thus in the hormone treated group the Blatt-Kupperman score fell from 12.1 to 6.4 and 3.2 in the third and sixth month respectively, while in the group receiving placebo the score fell from 11.5 to 6.3 in the third month and raised to 7.4 in the sixth month. Hamilton's test showed a significant improvement of depression only in patients under hormone therapy. Nineteen out of twenty five women using CCT had vaginal bleeding, showing no changes in the endometrial thickness during the study. Finally, HDL-cholesterol was raised in 14.5% while LDL-cholesterol was lowered in 18.7% (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Lipoproteins_MeSH S_blood_MeSH Lipoproteins_blood_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH P_Menopause_MeSH S_blood_MeSH Menopause_blood_MeSH M_Middle_Aged_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10550454
----K I
----T Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group.
----A A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Analysis_of_Variance_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH S_urine_MeSH Biological_Markers_urine_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Middle_Aged_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Osteoporosis__Postmenopausal_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH 
****** 10566625
----K E
----T The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.
----A Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH M_Apolipoprotein_A-I_MeSH S_analysis_MeSH Apolipoprotein_A-I_analysis_MeSH M_Apolipoproteins_B_MeSH S_blood_MeSH Apolipoproteins_B_blood_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Dehydroepiandrosterone_MeSH S_administration_&_dosage_MeSH Dehydroepiandrosterone_administration_&_dosage_MeSH S_blood_MeSH Dehydroepiandrosterone_blood_MeSH S_therapeutic_use_MeSH Dehydroepiandrosterone_therapeutic_use_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_blood_MeSH Dehydroepiandrosterone_Sulfate_blood_MeSH M_Dietary_Supplements_MeSH M_Double-Blind_Method_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Lipoprotein(a)_MeSH S_blood_MeSH Lipoprotein(a)_blood_MeSH M_Lipoproteins__HDL_MeSH S_blood_MeSH Lipoproteins__HDL_blood_MeSH M_Lipoproteins__LDL_MeSH S_blood_MeSH Lipoproteins__LDL_blood_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH P_Premenopause_MeSH P_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 10604047
----K E
----T Efficacy on climacteric symptoms of a new estradiol transdermal patch with active matrix in comparison with a reference reservoir patch. Two long-term randomized multicenter parallel-group studies.
----A METHODS: Two randomized prospective multicentre parallel group studies were performed (one in Germany and the other in Italy) in symptomatic postmenopausal women. The goal was to assess the efficacy on climacteric symptoms and the safety of a new estradiol (CAS 50-28-2) transdermal patch with solid active matrix (SAM) in comparison to a conventional liquid reservoir (LR) type estradiol transdermal patch. Both patches released 50 micrograms/day estradiol. One group of patients received the SAM patch and the other the LR patch in 4-week cycles, with a twice-weekly application of the patches for 3 weeks, followed by one week without patches. Progestin opposition was achieved with medroxyprogesterone acetate 5 mg/day orally in the last 11 days of patch application in the German study and with 10 mg/day in the last 12 days of patch application in the Italian study. Both studies were divided into two Parts: Part 1 with three 4-week cycles for a total of 12 weeks and Part 2 for other ten 4-weeks cycles in which the patches could be applied also continuously. The total duration of the study was therefore 52 weeks. RESULTS: Germany study. 133 patients resulted randomized to the SAM group and 129 to the LR group. Both estradiol patches quickly relieved climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the Kupperman Index. At the end of Part 1, in the SAM group 91% and in the LR group 96% of patients reported relief from climacteric symptoms. At the end of Part 2 the percentages were 98% and 95%, respectively. The two patches were therapeutically equivalent with a power greater than 99.7%. Both patches were systemically fairly well tolerated. Only 4.5% of patients in the SAM group and 3.9% in the LR group discontinued prematurely for possible adverse reactions related to estradiol. There was no significant difference between the two patches with regard to systemic tolerability. Conversely, with regard to local skin reactions, the SAM patch was significantly (p < 0.01) better tolerated than the LR patch. The adhesion to the skin of the SAM patches was better than that of the LR patches. RESULTS. Italian study. 139 patients resulted randomized to the SAM patch and 128 to the LR patch. Also in this study both types of patches relieved the climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the visual analogue scale (VAS) recordings of severity of hot flushes and of sweats. At the end of Part 1 both patches relieved 95% of patients from climacteric symptoms. At the end of Part 2, i.e. after 52 weeks, 100% of patients were relieved from climacteric symptoms. Of these, 72% in the SAM group and 78% in the LR group reported complete disappearance of symptoms. Also in the Italian study, therefore, the two patches were found therapeutically equivalent. Both patches stopped or even reversed bone mineral loss in L2-L4 and had some favorable effects on lipid metabolism. Both patches were systemically equally fairly well tolerated with premature discontinuations for systemic adverse drug reactions in only 5.0% of patients in the SAM group and 3.9% in the LR group. Conversely, as in the German study, the SAM patches were significantly better tolerated by the skin (p < 0.0001). CONCLUSIONS: The two types of estradiol transdermal patches were equivalent in providing an effective and rapid relief from climacteric symptoms. Systemically both patches were fairly well tolerated. The SAM patches were significantly better tolerated by the skin. The better local tolerability combined with better adhesion and cosmetic properties render the SAM patches very patient friendly and improve the compliance in the long term estrogen replacement therapy required to reduce osteoporosis and cardiovascular risks.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adhesiveness_MeSH M_Administration__Cutaneous_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_and_Bones_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Emotions_MeSH S_drug_effects_MeSH Emotions_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogens_MeSH S_blood_MeSH Estrogens_blood_MeSH M_Female_MeSH M_Hemorrhage_MeSH S_drug_therapy_MeSH Hemorrhage_drug_therapy_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Muscle__Smooth__Vascular_MeSH S_drug_effects_MeSH Muscle__Smooth__Vascular_drug_effects_MeSH S_physiology_MeSH Muscle__Smooth__Vascular_physiology_MeSH M_Vagina_MeSH S_physiology_MeSH Vagina_physiology_MeSH 
****** 10636492
----K E
----T Ten goals for the American College of Obstetricians and Gynecologists for the first decade of the next millennium.
----A 
----P Journal_Article 
----M P_Gynecology_MeSH M_Human_MeSH P_Obstetrics_MeSH M_Organizational_Objectives_MeSH M_Organizational_Policy_MeSH M_Societies__Medical_MeSH S_organization_&_administration_MeSH Societies__Medical_organization_&_administration_MeSH M_United_States_MeSH P_Women's_Health_MeSH 
****** 10636508
----K E
----T Nucleated red blood cells in healthy infants of women with gestational diabetes.
----A OBJECTIVE: To evaluate whether absolute nucleated red blood cell (RBC) counts are elevated in large-for-gestational-age (LGA) infants of women with gestational diabetes compared with appropriate-for-gestational-age (AGA) infants of women with or without gestational diabetes. METHODS: We compared absolute nucleated RBC counts during the first 12 hours of life in three groups of term, vaginally delivered infants, LGA infants of women with gestational diabetes (n = 20), AGA infants of women with gestational diabetes (n = 20), and AGA infants of nondiabetic women (n = 30). We excluded infants of women with hypertension, smoking, alcohol or drug abuse, and those with fetal heart rate abnormalities in labor, low Apgar scores, hemolysis, blood loss, or chromosomal anomalies. RESULTS: There were no significant differences among groups in gestational age, gravidity, parity, maternal analgesia, 1- and 5-minute Apgar scores, and lymphocyte counts. Corrected white blood cell counts and hematocrit were significantly higher in LGA infants of women with gestational diabetes than in the other groups. The median nucleated RBC count was significantly higher in LGA infants of women with gestational diabetes (0.56 x 10(9)/L, range 0-1.8 x 10(9)/L) than AGA infants of women with gestational diabetes (0.13 x 10(9)/L, range 0-0.65 x 10(9)/L) and controls (0.0005 x 10(9)/L, range 0-0.6 x 10(9)/L) (P < .001). Multiple regression analysis showed that absolute nucleated RBC count was significantly correlated with birth weight (or macrosomia) and maternal diabetic status (r2 = .25, P < .001 for the multiple regression, contribution of birth weight r2 = .19, and diabetes r2 = .06). CONCLUSION: At birth, term LGA infants born to women with gestational diabetes had higher absolute nucleated RBC counts compared with AGA infants born to women with gestational diabetes and controls.
----P Journal_Article 
----M M_Birth_Weight_MeSH S_physiology_MeSH Birth_Weight_physiology_MeSH P_Diabetes__Gestational_MeSH P_Erythroblasts_MeSH M_Female_MeSH M_Human_MeSH M_Infant__Newborn_MeSH S_blood_MeSH Infant__Newborn_blood_MeSH M_Male_MeSH M_Pregnancy_MeSH M_Prospective_Studies_MeSH 
****** 10649811
----K E
----T A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles.
----A OBJECTIVE: To compare the effects of two doses of conjugated equine estrogen (CEE) and two of esterified estrogen plus methyltestosterone (E + A) in surgically menopausal women. STUDY DESIGN: A two-year, parallel-group, double-blind study of 311 women who were randomly assigned to one of four regimens: (1) CEE, 0.625 mg/d; (2) CEE, 1.25 mg/d; (3) esterified estrogens, 0.625 mg, + methyltestosterone, 1.25 mg/d; or (4) esterified estrogens, 1.25, + methyltestosterone, 2.5 mg/d. Study parameters were symptoms, lipids, bone mineral density, side effects and safety. RESULTS: All treatments prevented loss of bone in the spine and hip. The higher E + A dose increased spine and hip BMD more than other treatments (P < .002). All treatments improved menopausal symptoms, with non-significantly greater improvements in well-being and sexual interest in the E + A groups. Similar and significant decreases in low-density lipoprotein were observed in all groups, but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups (P < .05). Hirsutism was uncommon and similar in all groups at two years. Discontinuation rates and reasons for withdrawal from the study were similar in both groups. No clinically significant side effects or laboratory test abnormalities were seen. CONCLUSION: As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH M_Equilin_MeSH S_pharmacology_MeSH Equilin_pharmacology_MeSH S_therapeutic_use_MeSH Equilin_therapeutic_use_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Libido_MeSH S_drug_effects_MeSH Libido_drug_effects_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH P_Menopause_MeSH M_Methyltestosterone_MeSH S_pharmacology_MeSH Methyltestosterone_pharmacology_MeSH S_therapeutic_use_MeSH Methyltestosterone_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Ovariectomy_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_Congeners_MeSH S_pharmacology_MeSH Testosterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Testosterone_Congeners_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 10657735
----K E
----T Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls: the impact of age and a two-week estradiol treatment.
----A In this placebo-controlled double-blind study, psychological and endocrine stress responses were investigated in healthy postmenopausal placebo-treated women (n = 15; 60-75 years; placebo via transdermal patches), healthy postmenopausal estradiol-treated women (n = 13; 60-79 years; 0.1 mg 17beta-estradiol daily via transdermal patches) and young controls (n = 15; 20-31 years; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the 'Trier Social Stress Test' (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 microgram hCRH after premedication with 1.5 mg Dex). Psychological parameters including perceived stressfulness, mood and subjective well-being were measured by visual analog scales, a mood questionnaire and a mood diary, respectively. Results show that the TSST induced significant increases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma cortisol and heart rates (all p < 0.0001). Regardless of age, comparable hormonal response patterns were observed in the TSST as indicated by similar peak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both age groups, hCRH injection after Dex premedication provoked significant increases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young controls in the Dex-CRH test (p < 0.025). Additional investigation of morning cortisol profiles could not reveal any age-related differences in basal hypothalamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatment, estradiol levels significantly increased only in substituted postmenopausal women (p < 0.001) reaching concentrations typically found in younger women during the follicular phase of the menstrual cycle. Corticosteroid-binding globulin levels did not differ significantly between groups. When confronted with the TSST, no response differences emerged between the three groups. However, estradiol treatment appeared to blunt the total plasma cortisol response in the Dex-CRH test, resulting in smaller increases in untreated premenopausal women and estradiol-treated postmenopausal women compared to placebo-treated postmenopausal women (p < 0.02). In sum, no response differences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, our data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement may modulate HPA feedback sensitivity in humans.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Age_Factors_MeSH M_Aged_MeSH M_Aging_MeSH S_drug_effects_MeSH Aging_drug_effects_MeSH M_Comparative_Study_MeSH M_Corticotropin_MeSH S_blood_MeSH Corticotropin_blood_MeSH M_Corticotropin-Releasing_Hormone_MeSH S_diagnostic_use_MeSH Corticotropin-Releasing_Hormone_diagnostic_use_MeSH M_Dexamethasone_MeSH S_diagnostic_use_MeSH Dexamethasone_diagnostic_use_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Feedback_MeSH S_physiology_MeSH Feedback_physiology_MeSH M_Glucocorticoids_MeSH S_diagnostic_use_MeSH Glucocorticoids_diagnostic_use_MeSH M_Heart_Rate_MeSH S_drug_effects_MeSH Heart_Rate_drug_effects_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_analysis_MeSH Hydrocortisone_analysis_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH M_Hypothalamo-Hypophyseal_System_MeSH S_drug_effects_MeSH Hypothalamo-Hypophyseal_System_drug_effects_MeSH S_physiopathology_MeSH Hypothalamo-Hypophyseal_System_physiopathology_MeSH M_Middle_Aged_MeSH M_Pituitary-Adrenal_System_MeSH S_drug_effects_MeSH Pituitary-Adrenal_System_drug_effects_MeSH S_physiopathology_MeSH Pituitary-Adrenal_System_physiopathology_MeSH M_Postmenopause_MeSH M_Premenopause_MeSH M_Saliva_MeSH S_chemistry_MeSH Saliva_chemistry_MeSH M_Stress__Psychological_MeSH S_physiopathology_MeSH Stress__Psychological_physiopathology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10663358
----K E
----T Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers.
----A In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the (45)Ca single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937 mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0. 25 microg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (+/- 0.35 SD) to 0.58 (+/- 0. 22), Dalpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Dalpha = +0.16 (+/- 0. 30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha >/=0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Calcitriol_MeSH S_administration_&_dosage_MeSH Calcitriol_administration_&_dosage_MeSH S_metabolism_MeSH Calcitriol_metabolism_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH S_metabolism_MeSH Calcium_metabolism_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Intestinal_Absorption_MeSH S_physiology_MeSH Intestinal_Absorption_physiology_MeSH M_Malabsorption_Syndromes_MeSH S_complications_MeSH Malabsorption_Syndromes_complications_MeSH S_metabolism_MeSH Malabsorption_Syndromes_metabolism_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_metabolism_MeSH Osteoporosis__Postmenopausal_metabolism_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10674594
----K E
----T Estrogen effects on postural balance in postmenopausal women without vasomotor symptoms: a randomized masked trial.
----A OBJECTIVE: To assess whether estrogen treatment given to postmenopausal women without vasomotor symptoms improves balance more than placebo. METHODS: Forty healthy postmenopausal women without vasomotor symptoms were randomized to transdermal 17beta-estradiol (E2) 50 microg/day for 14 weeks or identical transdermal placebo patches. Postural balance was measured with dynamic posturography before and after 4, 12, and 14 weeks of therapy. In this test, the visual, vestibular, and somatosensory systems were provoked with increasing difficulty and body sway was measured with a dual forceplate. A low score showed large sway and a score of 100 showed no sway at all. RESULTS: Thirty-eight women completed the study. Both groups had normal balance for their ages and near maximum scores in the three easier balance tests at baseline. In the most difficult test, both groups improved their postural balance significantly (from 13 to 32 and from 22 to 39, respectively) after 4 weeks. Thereafter, no change was seen. One problem was low statistical power, but the relative change in balance did not differ between groups. The comparison did not show even a minute advantage of E2 over placebo, so a study with higher power would probably not have shown a more pronounced effect of estrogen than placebo. The change over time did not differ between groups, which indicates a significant learning effect. CONCLUSION: In women without vasomotor symptoms, estrogen therapy did not seem to increase postural balance significantly more than placebo. However, we could not rule out that estrogens affect postural balance in women with vasomotor symptoms.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Female_MeSH M_Hot_Flashes_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Musculoskeletal_Equilibrium_MeSH S_drug_effects_MeSH Musculoskeletal_Equilibrium_drug_effects_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Reference_Values_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10687882
----K I
----T Efficacy and tolerability of a new estradiol delivering matrix patch (Estraderm MX) in postmenopausal women.
----A OBJECTIVE: To examine the efficacy and tolerability of a new matrix patch delivering estradiol (E2 Matrix) at doses of 0.05 and 0.10 mg per day (Estraderm MX 50, 100) in the treatment of moderate to severe postmenopausal symptoms. METHODS: A total of 254 postmenopausal women were randomized to receive treatment with E2 Matrix 0.10 mg (N = 86), E2 Matrix 0.05 mg (N = 82), or placebo (N = 86) in a double-blind, double-dummy fashion for a period of 12 weeks continuously. Patches were applied twice weekly to the buttocks with each patient wearing two patches at all times. The primary efficacy criterion was the difference from baseline of the mean number of moderate to severe hot flushes per 24 h during the last 2 weeks of treatment. Other efficacy variables included reduction in hot flushes at 4 and 8 weeks, reduction in daytime flushing and night sweats, and Kupperman Index at 4, 8, and 12 weeks. RESULTS: E2 Matrix 0.10 and 0.05 mg were both significantly superior to placebo in reducing hot flushes per 24 h after 4, 8, and 12 weeks of treatment (P < 0.001). Also, for all other efficacy parameters studied, both dosage strengths of E2 Matrix were statistically significantly superior to placebo at all time points (P < 0.001). Local tolerability was good in both groups. A slight increase in estrogen related adverse effects (breast tenderness, leukorrhoea) was seen with the 0.10 mg patch. Adhesion of patches and compliance were good. Overall systemic tolerability was good in both treated groups. However, a 4.8% overall incidence of endometrial hyperplasia was observed in patients with an intact uterus. CONCLUSIONS: This new matrix patch offers an effective and well tolerated dosage form for delivery of 0.05 and 0.1 mg estradiol per day. It may be particularly suitable for those women who experience local sensitivity to alcohol-containing systems. In light of the observed hyperplasia after treatment in five patients, estrogen therapy should as yet be supplemented monthly with a progestogen in women with an intact uterus.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH 
****** 10714908
----K I
----T A double-blind, randomized, comparative study evaluating clinical effects of two sequential estradiol-progestogen combinations containing either desogestrel or medroxyprogesterone acetate in climacteric women.
----A OBJECTIVES: The aim of this study was to compare a new sequential estradiol-desogestrel (E2-DSG) hormone replacement regimen (Liseta) with one of the standard treatments i.e. estradiol valerate-medroxyprogesterone acetate (E2V-MPA) combination (Klimalet) regarding the alleviation of climacteric symptoms, vaginal bleeding pattern and the occurrence of adverse experiences. METHODS: In a multicenter study performed in Denmark, a total of 376 perimenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either E2-DSG (1.5 mg E2 for 24 days with 0.15 mg DSG for the last 12 days followed by a placebo tablet for 4 days) (n = 186) or with E2V-MPA (2 mg E2V for 21 days with 10 mg MPA for the last 10 days) (n = 190). Treatments were administered, using a double-blind, double-dummy technique for 6 cycles of 28 days. RESULTS: Three hundred and seventeen women, 158 in the E2-DSG and 159 in the E2V-MPA group, completed six treatment cycles. Both treatments reduced menopausal symptoms rapidly and to a similar extent. Hot flushes were present in 88% of the women in both groups. After six treatment cycles, hot flushes were no longer present in 71 and 62% of the women in the E2-DSG and E2V-MPA group, respectively. Perspiration decreased from 80 to 65% in the E2-DSG group and from 82 to 63% in the E2V-MPA group. Mood disturbances were present in 82% of the women in the E2-DSG at baseline, and in 52% after six cycles. In the E2V-MPA group the corresponding figures were 68 and 42%, respectively. The bleeding pattern was comparable in both treatment groups. Regular withdrawal (expected) bleeding appeared in 90-92% and in 85-90% of the women in cycles 1-5 with E2-DSG and E2V-MPA, respectively. Irregular bleeding (including spotting) occurred in 15.2% of the women receiving E2-DSG and in 20.1% of the women treated with E2V-MPA in cycle 6. In both treatment groups there was a tendency of a slight decrease in blood pressure. Adverse events were in less than 10% in each group the reason to discontinue treatment. CONCLUSIONS: Both treatments effectively alleviated menopausal complaints and presented good cycle control. Bleeding pattern and mood disturbances appeared to be more favorable influenced by E2-DSG.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Desogestrel_MeSH S_administration_&_dosage_MeSH Desogestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Desogestrel_adverse_effects_MeSH S_therapeutic_use_MeSH Desogestrel_therapeutic_use_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Flushing_MeSH S_prevention_&_control_MeSH Flushing_prevention_&_control_MeSH M_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Mood_Disorders_MeSH S_prevention_&_control_MeSH Mood_Disorders_prevention_&_control_MeSH M_Placebos_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Sweating_MeSH S_drug_effects_MeSH Sweating_drug_effects_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH 
****** 10714909
----K I
----T Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints.
----A OBJECTIVES: To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch (Fem7, Merck KGaA, Germany) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo. DESIGN: A multicentre, randomized, double-blind study with an initial screening phase (phase I), a 3-month double-blind placebo-controlled phase (phase II) and a 3-month open follow-up phase (phase III). METHODS: 186 patients were randomized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up (total duration; 6 months). The changes in Kupperman Index (primary efficacy variable), hot flushes and urogenital symptom score were studied from baseline to the end of the study. In addition, skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy. RESULTS: A reduction in Kupperman Index was observed in both groups, and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo (last value vs. baseline P = 0.0006). From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group. The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase (mean weekly hot flush reduction at the end of the placebo-controlled treatment phase: -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo, P = 0.0025). The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1-3 and 4-7. Subjective acceptance of the 7-day-Estradiol patch was good and 72.4% of patients who took active medication throughout the study were willing to consider continuing its use. CONCLUSIONS: The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women, with a rapid onset of action and 7-day duration of therapeutic effect. Although a placebo effect was observed, the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period.
----P Clinical_Trial Clinical_Trial__Phase_II Clinical_Trial__Phase_III Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Comparative_Study_MeSH M_Data_Interpretation__Statistical_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Flushing_MeSH S_prevention_&_control_MeSH Flushing_prevention_&_control_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH P_Hysterectomy_MeSH M_Middle_Aged_MeSH M_Patient_Compliance_MeSH M_Patient_Satisfaction_MeSH M_Placebo_Effect_MeSH M_Placebos_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Safety_MeSH M_Skin_MeSH S_drug_effects_MeSH Skin_drug_effects_MeSH M_Urinary_Incontinence_MeSH S_prevention_&_control_MeSH Urinary_Incontinence_prevention_&_control_MeSH M_Vaginal_Diseases_MeSH S_prevention_&_control_MeSH Vaginal_Diseases_prevention_&_control_MeSH 
****** 10714911
----K E
----T Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women.
----A BACKGROUND: The main goals of estrogen replacement therapy (ERT) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life (QL). Androgens and tibolone therapy may increase bone mineral density (BMD) to a greater extent than ERT and offer an increase in QL. Lipid and cardiovascular effects, however, are still a major concern. AIM: To evaluate whether the addition of a weak androgen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy. SUBJECTS AND METHODS: This prospective study enrolled 120 surgical postmenopausal women; of these, 96 completed the 1-year follow-up. Patients were allocated to one of four groups. The first group (A; n = 23) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydroandrosterone im monthly. The second group (E; n = 26) received 50 microg/day of transdermal 17-b-estradiol continuously; the third (T; n = 23) received 2.5 mg of tibolone every day; and finally, the fourth group (C; n = 24) constituted a treatment-free control group. Bone mass (dual X-ray absorptiometry), serum total cholesterol, HDL, LDL, triglycerides, apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up. RESULTS: All active treatment groups showed an increase in BMD. This increase was higher in the A treatment group (4.08% P < 0.01). Sexuality improved significantly with therapy; however, tibolone and androgens increased scores to a greater extent than ERT. Androgen therapy was associated with significant increases in total cholesterol, LDL and triglycerides. Cholesterol and LDL fall into groups E and T, HDL into groups A and T and triglycerides in group T only. CONCLUSION: The combined regimen of androgens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone; its effects on lipids, however, are clearly adverse.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Anabolic_Agents_MeSH S_administration_&_dosage_MeSH Anabolic_Agents_administration_&_dosage_MeSH S_therapeutic_use_MeSH Anabolic_Agents_therapeutic_use_MeSH M_Apolipoprotein_A-I_MeSH S_blood_MeSH Apolipoprotein_A-I_blood_MeSH M_Apolipoproteins_B_MeSH S_blood_MeSH Apolipoproteins_B_blood_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_and_Bones_MeSH S_drug_effects_MeSH Bone_and_Bones_drug_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Comparative_Study_MeSH M_Dehydroepiandrosterone_MeSH S_administration_&_dosage_MeSH Dehydroepiandrosterone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Dehydroepiandrosterone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Dehydroepiandrosterone_therapeutic_use_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Prospective_Studies_MeSH M_Sexuality_MeSH S_drug_effects_MeSH Sexuality_drug_effects_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 10745058
----K E
----T Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.
----A BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aging_MeSH S_metabolism_MeSH Aging_metabolism_MeSH S_physiology_MeSH Aging_physiology_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH S_physiology_MeSH Cognition_physiology_MeSH M_Gonadal_Steroid_Hormones_MeSH S_physiology_MeSH Gonadal_Steroid_Hormones_physiology_MeSH M_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Injections_MeSH M_Male_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH S_physiology_MeSH Memory_physiology_MeSH M_Neuropsychological_Tests_MeSH M_Practice_(Psychology)_MeSH M_Space_Perception_MeSH S_drug_effects_MeSH Space_Perception_drug_effects_MeSH S_physiology_MeSH Space_Perception_physiology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH S_pharmacology_MeSH Testosterone_pharmacology_MeSH S_physiology_MeSH Testosterone_physiology_MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH S_physiology_MeSH Verbal_Learning_physiology_MeSH 
****** 10758784
----K I
----T Efficacy on climacteric symptoms and safety of low dose estradiol transdermal matrix patches. A randomized, double-blind placebo-controlled study.
----A Two estradiol (E2) transdermal patches releasing 25 micrograms/day E2 (D-25) or 37.5 micrograms/day E2 (D-37.5) were compared to a placebo patch on 156 patients in natural or surgical menopause suffering from at least 5 hot flushes per day, randomly and blindly assigned to three parallel groups of 52 patients each, to be treated continuously for 12 weeks, without progestin opposition. "Responders" (patients with less than 3 hot flushes per day at the end of treatment), were 82% and 90% under D-25 or D-37.5, respectively, both significantly (p < 0.001) more than under placebo (44%). Comparable efficacy was observed on severity of hot flushes, Kupperman Index and on the self-rated efficacy. Systemic adverse events occurred in 10%, 10% and 8% of patients, respectively, under D-25, D-37.5 or placebo. Occasional mild and transient itching and/or erythema on the site of application was reported by few patients and did never require discontinuation of application. In conclusion D-25 and D-37.5 were significantly more effective than placebo in relieving climacteric symptoms and were systemically and locally as well tolerated as placebo. D-25 (Demestril 25) releasing 25 micrograms/day E2 can therefore be recommended for low-dosed estrogen replacement therapy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Prospective_Studies_MeSH 
****** 10761538
----K E
----T Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine Group.
----A A randomized, multicenter, double-blind, parallel group study was performed to assess the effects of a standardized ginseng extract compared with those of a placebo on quality of life (QoL) and on physiological parameters in symptomatic postmenopausal women. Validated questionnaires [Psychological General Well-Being (PGWB) index, Women's Health Questionnaire (WHQ)] and Visual Analogue (VA) scales were used to assess the effects of the extract on QoL at baseline and after 16 weeks' treatment with either the ginseng extract or placebo. To assess the efficacy of ginseng on postmenopausal symptoms, physiological parameters [follicle-stimulating hormone (FSH) and estradiol levels, endometrial thickness, maturity index and vaginal pH] were recorded at the same time points. Of the 384 randomized patients (mean age 53.5 +/- 4.0 years), the questionnaires were completed by 193 women treated with ginseng and 191 treated with placebo. With regard to the primary endpoint (total score of the PGWB index) the extract showed only a tendency for a slightly better overall symptomatic relief (p < 0.1). Exploratory analysis of PGWB subsets, however, reported p-values < 0.05 for depression, well-being and health subscales in favor of ginseng compared with placebo. No statistically significant effects were seen for the WHQ and the VA scales or the physiological parameters, including vasomotor symptoms (hot flushes). The positive effects of ginseng on health-related QoL in menopausal women should be further investigated. This study shows, however, that the beneficial effects of ginseng are most likely not mediated by hormone replacement-like effects, as physiological parameters such as FSH and estradiol levels, endometrial thickness, maturity index and vaginal pH were not affected by the treatment.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Panax_MeSH S_therapeutic_use_MeSH Panax_therapeutic_use_MeSH P_Phytotherapy_MeSH P_Plants__Medicinal_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10760294
----K E
----T Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.
----A The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a "young" concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create "supermen/women" (doping).
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article 
----M M_Aged_MeSH M_Aging_MeSH S_blood_MeSH Aging_blood_MeSH S_physiology_MeSH Aging_physiology_MeSH M_Blood_Vessels_MeSH S_drug_effects_MeSH Blood_Vessels_drug_effects_MeSH M_Bone_Remodeling_MeSH M_Dehydroepiandrosterone_MeSH S_blood_MeSH Dehydroepiandrosterone_blood_MeSH S_pharmacology_MeSH Dehydroepiandrosterone_pharmacology_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_blood_MeSH Dehydroepiandrosterone_Sulfate_blood_MeSH S_pharmacology_MeSH Dehydroepiandrosterone_Sulfate_pharmacology_MeSH M_Densitometry__X-Ray_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_I_metabolism_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH M_Sebum_MeSH S_metabolism_MeSH Sebum_metabolism_MeSH M_Sexuality_MeSH M_Skin_MeSH S_metabolism_MeSH Skin_metabolism_MeSH M_Skin_Pigmentation_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10775738
----K I
----T Initial 17beta-estradiol dose for treating vasomotor symptoms.
----A OBJECTIVE: To compare the efficacy of different doses of 17beta-estradiol (E2) for relief of vasomotor symptoms in menopausal women. METHODS: This was a randomized, double-masked, placebo-controlled, 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg, 0.5 mg, 1 mg, or 2 mg oral micronized 17beta-E2, or placebo. The number and severity of hot flushes were recorded daily. RESULTS: There was a significant linear correlation between increased dosage of 17beta-E2 and decreased moderate to severe hot flushes per week (P <.001). Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg, showing a significant difference from placebo at week 4 (P <.05). At week 4, half the women on placebo had reduced moderate to severe hot flushes of at least 52%; the corresponding figures were 56%, 69%, 86%, and 91% for 0.25, 0.5, 1, and 2 mg, respectively. At week 12, all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes (P <.001). Although there were no significant differences, twice as many women in the 2-mg group discontinued treatment due to adverse events, compared with the placebo group. CONCLUSION: Oral micronized 17beta-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women. 17beta-E2 1 mg appeared to be the most useful initial dose.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10797125
----K E
----T Estrogen modifies the temperature effects of progesterone.
----A To test the hypothesis that progestin-mediated increases in resting core temperature and the core temperature threshold for sweating onset are counteracted by estrogen, we studied eight women (24 +/- 2 yr) at 27 degrees C rest, during 20 min of passive heating (35 degrees C), and during 40 min of exercise at 35 degrees C. Subjects were tested four times, during the early follicular and midluteal menstrual phases, after 4 wk of combined estradiol-norethindrone (progestin) oral contraceptive administration (OC E+P), and after 4 wk of progestin-only oral contraceptive administration (OC P). The order of the OC P and OC E+P were randomized. Baseline esophageal temperature (T(es)) at 27 degrees C was higher (P < 0.05) in the luteal phase (37.08 +/- 0.21 degrees C) and in OC P (37.60 +/- 0.31 degrees C) but not during OC E+P (37.04 +/- 0.23 degrees C) compared with the follicular phase (36.66 +/- 0.21 degrees C). T(es) remained above follicular phase levels throughout passive heating and exercise during OC P, whereas T(es) in the luteal phase was greater than in the follicular phase throughout exercise (P < 0.05). The T(es) threshold for sweating was also greater in the luteal phase (38.02 +/- 0.28 degrees C) and OC P (38.07 +/- 0.17 degrees C) compared with the follicular phase (37.32 +/- 0.11 degrees C) and OC E+P (37.46 +/- 0.18 degrees C). Progestin administration raised the T(es) threshold for sweating during OC P, but this effect was not present when estrogen was administered with progestin, suggesting that estrogen modifies progestin-related changes in temperature regulation. These data are also consistent with previous findings that estrogen lowers the thermoregulatory operating point.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Body_Temperature_MeSH S_drug_effects_MeSH Body_Temperature_drug_effects_MeSH S_physiology_MeSH Body_Temperature_physiology_MeSH M_Contraceptives__Oral_MeSH S_pharmacology_MeSH Contraceptives__Oral_pharmacology_MeSH M_Differential_Threshold_MeSH S_drug_effects_MeSH Differential_Threshold_drug_effects_MeSH M_Drug_Combinations_MeSH M_Esophagus_MeSH S_physiology_MeSH Esophagus_physiology_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogens_MeSH S_physiology_MeSH Estrogens_physiology_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Female_MeSH M_Follicular_Phase_MeSH S_physiology_MeSH Follicular_Phase_physiology_MeSH M_Human_MeSH M_Luteal_Phase_MeSH S_physiology_MeSH Luteal_Phase_physiology_MeSH M_Norethindrone_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH M_Progesterone_MeSH S_pharmacology_MeSH Progesterone_pharmacology_MeSH S_physiology_MeSH Progesterone_physiology_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Sweating_MeSH S_drug_effects_MeSH Sweating_drug_effects_MeSH S_physiology_MeSH Sweating_physiology_MeSH 
****** 10805607
----K E
----T The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females.
----A RATIONALE: Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band. OBJECTIVE: The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously. METHODS: EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to mild mental stress. RESULTS: Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21+/-0.5 nmol/l). Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, as indicated by an increase in cortisol plasma levels. CONCLUSIONS: The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Analysis_of_Variance_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Frontal_Lobe_MeSH S_drug_effects_MeSH Frontal_Lobe_drug_effects_MeSH S_physiology_MeSH Frontal_Lobe_physiology_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH S_pharmacology_MeSH Hydrocortisone_pharmacology_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Psychomotor_Performance_MeSH S_drug_effects_MeSH Psychomotor_Performance_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Thinking_MeSH S_drug_effects_MeSH Thinking_drug_effects_MeSH 
****** 10810960
----K I
----T 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.
----A OBJECTIVES: The efficacy and safety of 25-microg 17beta-estradiol vaginal tablets (Vagifem) were assessed and compared with 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of menopausal-derived atrophic vaginitis, resulting from estrogen deficiency. DESIGN: In a multicenter, open-label, randomized, parallel-group study, 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream. Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle-stimulating hormone. Safety was monitored by the incidence of adverse events, evaluation of endometrial biopsies, and clinical laboratory results. Patients also assessed the acceptability of the study medications. RESULTS: Composite scores of vaginal symptoms (dryness, soreness, and irritation) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis. At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p < 0.001). Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream. Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream (p < or = 0.001). Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal (10% versus 32%). CONCLUSIONS: Treatment regimens with 25-microg 17beta-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Animals_MeSH M_Atrophy_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Horses_MeSH M_Human_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vagina_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Creams__Foams_and_Jellies_MeSH M_Vaginitis_MeSH S_drug_therapy_MeSH Vaginitis_drug_therapy_MeSH 
****** 10824236
----K E
----T Identification of early postmenopausal women with no bone response to HRT: results of a five-year clinical trial.
----A Hormone replacement therapy (HRT) prevents postmenopausal bone loss and fractures. However, the occurrence of women with no bone response to HRT has not been widely examined. We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women. The study population was a subsample of the Kuopio Osteoporosis Study (n = 14,220). A total of 464 early postmenopausal women were randomized into four treatment groups: (1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate); (2) vitamin D3; (3) HRT + Vitamin D3 combined; and (4) placebo. In this study, the data from HRT and placebo groups were analyzed. Lumbar (L2-4) and femoral neck bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DXA) at baseline and after 5 years of treatment. A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change (+95% CI) of the placebo group or worse. Altogether, 74 women in the HRT group and 104 women in the placebo group complied with the treatment. According to spinal BMD analysis, 11% of the women were classified as densitometric nonresponders; the corresponding proportion for femoral BMD analysis was 26%. Both smoking (p = 0.003) and low body weight (p = 0.028) were significant risk factors for densitometric nonresponse to HRT. After 6 months of treatment the densitometric nonresponders (hip) had a significantly higher mean serum follicle stimulating hormone (FSH) level (p = 0.038) and lower increases in serum estradiol levels (p = 0.006) than the densitometric responders. The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders (spine) than responders (p = 0.043 and 0.017, respectively). In conclusion, this prospective study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT. Repeated serum FSH, estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH M_Body_Weight_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_and_Bones_MeSH S_physiopathology_MeSH Bone_and_Bones_physiopathology_MeSH M_Cholecalciferol_MeSH S_metabolism_MeSH Cholecalciferol_metabolism_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_metabolism_MeSH Estrogens_metabolism_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_blood_MeSH Osteoporosis__Postmenopausal_blood_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Prospective_Studies_MeSH M_Smoking_MeSH S_adverse_effects_MeSH Smoking_adverse_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Failure_MeSH 
****** 10831472
----K E
----T Effects of gonadal steroids in women with a history of postpartum depression.
----A OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Cross-Sectional_Studies_MeSH M_Depression__Postpartum_MeSH S_blood_MeSH Depression__Postpartum_blood_MeSH S_diagnosis_MeSH Depression__Postpartum_diagnosis_MeSH S_physiopathology_MeSH Depression__Postpartum_physiopathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_physiology_MeSH Estradiol_physiology_MeSH M_Female_MeSH M_Human_MeSH M_Hypogonadism_MeSH S_blood_MeSH Hypogonadism_blood_MeSH S_etiology_MeSH Hypogonadism_etiology_MeSH S_physiopathology_MeSH Hypogonadism_physiopathology_MeSH M_Leuprolide_MeSH S_diagnostic_use_MeSH Leuprolide_diagnostic_use_MeSH S_pharmacology_MeSH Leuprolide_pharmacology_MeSH M_Middle_Aged_MeSH M_Mood_Disorders_MeSH S_etiology_MeSH Mood_Disorders_etiology_MeSH M_Personality_Inventory_MeSH S_statistics_&_numerical_data_MeSH Personality_Inventory_statistics_&_numerical_data_MeSH M_Placebos_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_blood_MeSH Progesterone_blood_MeSH S_physiology_MeSH Progesterone_physiology_MeSH M_Psychiatric_Status_Rating_Scales_MeSH S_statistics_&_numerical_data_MeSH Psychiatric_Status_Rating_Scales_statistics_&_numerical_data_MeSH M_Substance_Withdrawal_Syndrome_MeSH S_blood_MeSH Substance_Withdrawal_Syndrome_blood_MeSH S_etiology_MeSH Substance_Withdrawal_Syndrome_etiology_MeSH S_physiopathology_MeSH Substance_Withdrawal_Syndrome_physiopathology_MeSH 
****** 10857213
----K E
----T [Long-term side-effects following cyproterone acetate containing therapy in gynecology]
----A It has been suggested that cyproterone acetate (CPA) has a mutagenic potency. It has been postulated that a threshold dosage of CPA has mutagenic effects, but in the same way data have been published documenting that a continuous low dosage of cyproterone acetate leads to a reduction of mutagenic episodes. Despite published data about higher levels of DNA adduct creations due to CPA an international multicentre study analysing 2,506 patients with 7,971 patient-years that used CPA could not find any liver cell cancers, even if due to epidemiological data 6 liver cell cancers should have occurred upon this study group. The present study deals with the evaluation of 57 women which received CPA in combination with EE2 11-13 years before. The daily dosage was 2 mg CPA in combination with 35 mg or 50 mg EE2. In Germany these drugs were registered under the name of Diane 35 or Diane 50. Long-term follow-up evaluation concerning side effects, especially the appearance of liver cell carcinomas, were the aim of this study. With the records of 32% (18/57) of the above mentioned patient group the following long-term follow-up side effects could be observed: 1) weight gain, 2) headache, 3) migraine, 4) gastrointestinal disorders, 5) mood affections/depressions, 6) oedema of the legs, 7) skin affections, 8) mastodynia. No benign liver tumor or liver cell carcinoma was detected upon our group of investigated patients. In conclusion we can affirm that the use of CPA in a dosage of 2 mg per day does not lead to serious side effects under long-term follow-up observation conditions and that it's use does not correlate with a higher appearance of liver cell carcinomas.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Androgen_Antagonists_MeSH S_administration_&_dosage_MeSH Androgen_Antagonists_administration_&_dosage_MeSH S_adverse_effects_MeSH Androgen_Antagonists_adverse_effects_MeSH M_Carcinoma__Hepatocellular_MeSH S_chemically_induced_MeSH Carcinoma__Hepatocellular_chemically_induced_MeSH S_diagnosis_MeSH Carcinoma__Hepatocellular_diagnosis_MeSH M_Cyproterone_Acetate_MeSH S_administration_&_dosage_MeSH Cyproterone_Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Cyproterone_Acetate_adverse_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Combinations_MeSH M_English_Abstract_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hirsutism_MeSH S_drug_therapy_MeSH Hirsutism_drug_therapy_MeSH M_Human_MeSH M_Liver_Neoplasms_MeSH S_chemically_induced_MeSH Liver_Neoplasms_chemically_induced_MeSH S_diagnosis_MeSH Liver_Neoplasms_diagnosis_MeSH M_Risk_Factors_MeSH 
****** 10875847
----K E
----T Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone.
----A This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.
----P Journal_Article 
----M M_Adult_MeSH M_Embryo_Transfer_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH P_Fertilization_in_Vitro_MeSH M_Human_MeSH M_Luteal_Phase_MeSH S_drug_effects_MeSH Luteal_Phase_drug_effects_MeSH M_Menstruation_MeSH S_physiology_MeSH Menstruation_physiology_MeSH M_Middle_Aged_MeSH M_Osmolar_Concentration_MeSH M_Powders_MeSH M_Pregnancy_MeSH M_Pregnancy_Outcome_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Retrospective_Studies_MeSH P_Sperm_Injections__Intracytoplasmic_MeSH 
****** 10931767
----K E
----T Sex steroids modify working memory.
----A In the last ten years, numerous mechanisms by which sex steroids modify cortical function have been described. For example, estrogen replacement improves verbal memory in women, and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function. Little is known about sex steroid effects on other aspects of memory, such as frontal lobe-mediated working memory. We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women. Before hormone supplementation, working memory, tested with the Subject Ordered Pointing Test (SOP), was worse in older subjects than younger subjects, and there was no evidence of gender differences at either age. Testosterone supplementation improved working memory in older men, but a similar enhancement of working memory was not found in older women supplemented with estrogen. In men, testosterone and estrogen effects were reciprocal - with better working memory related to a higher testosterone to estrogen ratio. These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aging_MeSH S_drug_effects_MeSH Aging_drug_effects_MeSH S_physiology_MeSH Aging_physiology_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH S_physiology_MeSH Cognition_physiology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Gonadal_Steroid_Hormones_MeSH S_administration_&_dosage_MeSH Gonadal_Steroid_Hormones_administration_&_dosage_MeSH S_blood_MeSH Gonadal_Steroid_Hormones_blood_MeSH M_Human_MeSH M_Male_MeSH M_Memory__Short-Term_MeSH S_drug_effects_MeSH Memory__Short-Term_drug_effects_MeSH S_physiology_MeSH Memory__Short-Term_physiology_MeSH M_Middle_Aged_MeSH M_Regression_Analysis_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 10945511
----K I
----T An estradiol matrix transdermal system for the prevention of postmenopausal bone loss.
----A OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and tolerability of 2 years' application of an estradiol matrix transdermal system for the prevention of postmenopausal bone loss. METHODS: In this multicenter, randomized, placebo-controlled, parallel-group study, 261 surgically or naturally postmenopausal women were randomized to apply the estradiol matrix transdermal system (0.025, 0.0375, 0.05, or 0.1 mg/d) or matching placebo twice a week for 2 years. The study was double blind with respect to treatment (active vs placebo) but not to the dose levels of active treatment (because of the differing sizes and shapes of the patches). In addition to receiving the assigned treatment, the 100 nonhysterectomized women received 2.5 mg medroxyprogesterone acetate daily throughout the study. RESULTS: The evaluable group (n = 259) had a mean age of 52 years and a mean duration of menopause of 32 months. Following 2 years of treatment, there were significant differences in favor of estradiol between all doses of the estradiol matrix transdermal system and placebo in terms of the percentage change from baseline in the bone mineral density (BMD) of the L1-L4 anteroposterior lumbar spine (0.1 and 0.05 mg/d, P < 0.001; 0.0375 mg/d, P = 0.024; 0.025 mg/d, P = 0.002). Percentage changes from baseline in the BMD of the femoral neck after 2 years of treatment also consistently demonstrated the efficacy of the estradiol matrix transdermal system compared with placebo (all, P < or = 0.044). The estradiol matrix transdermal system was well tolerated. CONCLUSION: The estradiol matrix transdermal system was effective in preventing postmenopausal bone loss at dosages of 0.025 to 0.1 mg/d, and had a safety profile consistent with the known effects of estrogen/progestin.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Bone_Density_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10979796
----K E
----T Alendronate for the treatment of osteoporosis in men.
----A BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alendronate_MeSH S_pharmacology_MeSH Alendronate_pharmacology_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Analysis_of_Variance_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH S_urine_MeSH Biological_Markers_urine_MeSH M_Body_Height_MeSH S_drug_effects_MeSH Body_Height_drug_effects_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Calcium_MeSH S_blood_MeSH Calcium_blood_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH S_physiopathology_MeSH Osteoporosis_physiopathology_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Phosphates_MeSH S_blood_MeSH Phosphates_blood_MeSH M_Spinal_Fractures_MeSH S_epidemiology_MeSH Spinal_Fractures_epidemiology_MeSH S_prevention_&_control_MeSH Spinal_Fractures_prevention_&_control_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 10960626
----K E
----T Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial.
----A OBJECTIVE: To assess the effects of raloxifene, estrogen, and placebo on quality of life in healthy, asymptomatic, postmenopausal women. METHODS: In a multicenter, double-blind, 12-month study, 398 women were assigned randomly to one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100); conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The Women's Health Questionnaire, a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and 3-month intervals. RESULTS: Overall, quality of life from baseline to end point was preserved equally in all treatment groups. Six domains (depressed mood, somatic symptoms, memory/concentration, sexual behavior, sleep problems, and perceived attractiveness) were unchanged in all groups. Three domains (menstrual symptoms, vasomotor symptoms, and anxiety/fears) were statistically significantly different among groups. Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment (P <.05), irrespective of previous hormone replacement therapy, baseline estradiol (E2) levels, or years postmenopause. CONCLUSION: Most quality-of-life domains were not affected by treatment with estrogen or raloxifene. Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved anxiety levels in postmenopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estrogen_Receptor_Modulators_MeSH S_adverse_effects_MeSH Estrogen_Receptor_Modulators_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogen_Receptor_Modulators_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Quality_of_Life_MeSH M_Raloxifene_MeSH S_adverse_effects_MeSH Raloxifene_adverse_effects_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10960627
----K E
----T Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate and ethinyl estradiol combinations. The FemHRT Study Investigators.
----A OBJECTIVE: To determine the effect of continuous combined treatment with norethindrone acetate and ethinyl estradiol (E2) on vaginal bleeding, spotting, or bleeding and/or spotting in postmenopausal women. METHODS: Two randomized clinical trials were conducted in which participants recorded information on the daily occurrence of vaginal bleeding or spotting. In study 1, 219 postmenopausal women reporting at least ten hot flushes per week were randomized to placebo or one of four treatment groups (0.2 mg norethindrone acetate/1 microg ethinyl E2, 0.5 mg norethindrone acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5 microg ethinyl E2, or 1 mg norethindrone acetate/10 microg ethinyl E2). In study 2, 266 postmenopausal women reporting at least 56 moderate to severe hot flushes were randomized to placebo or one of three treatment groups (0.5 mg norethindrone acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5 microg ethinyl E2, or 1 mg norethindrone acetate/10 microg ethinyl E2). The total duration of treatment was 16 weeks in study 1 and 12 weeks in study 2. In both studies, subjects reported in daily diaries whether they had either bleeding or spotting.Results: In study 1, there was a significantly greater relative risk (RR) for bleeding in the group receiving 1 mg norethindrone acetate/10 microg ethinyl E2 at study weeks 4 and 8 (RR = 1.36 and 95% confidence interval [CI] 1.01, 1.83; RR = 1.37 and 95% CI 1.1, 1.72; respectively) compared with placebo, but not at study weeks 12 or 16. The group receiving 1 mg norethindrone acetate/5 microg ethinyl E2 also had a significantly greater risk at weeks 4 and 8 (RR = 1.5 and 95% CI 1.15, 1.96; RR = 1.33 and 95% CI 1.00, 1.77; respectively), whereas the other dose combinations did not differ from placebo. Results from study 2 were similar to those of study 1.Conclusion: Although there was a greater risk for bleeding and/or spotting at the higher doses of norethindrone acetate and ethinyl E2, this risk declined over time. If compliance with hormone replacement therapy regimens is influenced at least in part by vaginal bleeding, the combined norethindrone acetate/ethinyl E2 regimen investigated in these studies may provide a treatment option.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Risk_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH 
****** 10993030
----K I
----T Suppression of vasomotor and vulvovaginal symptoms with continuous oral 17beta-estradiol.
----A OBJECTIVES: To evaluate the efficacy and safety of different doses of 173-estradiol for the treatment of vasomotor and vulvovaginal symptoms. DESIGN: This was a randomized, double-blind, multicenter, parallel-group study. One hundred forty-five subjects, including naturally postmenopausal women aged 40-60 (who had not experienced menses for at least 12 months), women who had undergone hysterectomy, and women aged 25-60 who had undergone bilateral oophorectomy with or without hysterectomy were studied. Either placebo or 17beta-estradiol (1 mg or 0.5 mg) was given orally every day for 12 weeks, and vasomotor symptoms and vaginal epithelial cytology were evaluated. RESULTS: There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes (all hot flushes, 1 mg vs. placebo, p < 0.00 1; 0.5 mg vs. placebo, p = 0.007), with a more substantial proportion of subjects responding in the 1-mg group (mean change in mean number of hot flushes of 83.2%). Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells (end-of-treatment mean values of 0%, 78.5%, and 21.5% for parabasal, intermediate, and superficial cells, respectively, in the 1-mg group; mean values of 0.3%, 80.8%, and 18.9% in the 0.5-mg group; and mean values of 15.2%, 74.7%, and 10.2% in the placebo group). The proportion of subjects reporting no vaginal dryness was greatest in the 1-mg group (mean percentage of days without dryness of 86.1% at weeks 9-12). CONCLUSIONS: For the relief of vasomotor and vulvovaginal symptoms, 17beta-estradiol I mg is effective and has an excellent safety profile.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Atrophy_MeSH S_prevention_&_control_MeSH Atrophy_prevention_&_control_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_United_States_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Diseases_MeSH S_pathology_MeSH Vaginal_Diseases_pathology_MeSH S_prevention_&_control_MeSH Vaginal_Diseases_prevention_&_control_MeSH M_Vulvar_Diseases_MeSH S_pathology_MeSH Vulvar_Diseases_pathology_MeSH S_prevention_&_control_MeSH Vulvar_Diseases_prevention_&_control_MeSH 
****** 10989241
----K E
----T Resting ECG is modified after oophorectomy and regresses with estrogen replacement therapy in premenopausal women.
----A OBJECTIVE: To assess the effects of bilateral oophorectomy on the resting ECG and whether they regress with estrogen replacement therapy. STUDY DESIGN: Twenty-six premenopausal and 15 postmenopausal women were enrolled in the present study. All women had undergone hysterectomy and bilateral ovariectomy. All women underwent 12-lead ECG on admission to hospital. A second ECG was recorded 20-25 days after surgery. After this second ECG, premenopausal women were randomly divided into two groups. The women of Group A (n=14) received transdermal ethinyl estradiol (EE). The women of Group B (n=12) did not receive any therapy. A third ECG was performed in both groups 30-35 days after randomization. RESULTS: Bilateral oophorectomy did not induce any significant modifications in the ECG parameters of the postmenopausal women whereas in the premenopausal women, we observed a significant increment in mean duration of the T wave, a significant decrease in its amplitude and significant reduction in ST depression in V2, V3, V4 and V5. The third ECG showed regression of the ECG modifications in Group A. In the women of Group B, the second and third ECGs were not substantially different, but there were statistically significant differences between the first and third ECGs. CONCLUSIONS: The results of the present study show that ovariectomy induces significant though not clinically evident modifications in resting ECG. These ECG changes are probably due to the sudden reduction in sex hormone plasma levels after ovariectomy. Administration of estradiol induced regression of the ECG modifications.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Electrocardiography_MeSH S_drug_effects_MeSH Electrocardiography_drug_effects_MeSH M_Estradiol_Congeners_MeSH S_administration_&_dosage_MeSH Estradiol_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_Congeners_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Ethinyl_Estradiol_pharmacology_MeSH M_Female_MeSH M_Heart_MeSH S_drug_effects_MeSH Heart_drug_effects_MeSH S_physiology_MeSH Heart_physiology_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Ovariectomy_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Postoperative_Period_MeSH M_Premenopause_MeSH S_drug_effects_MeSH Premenopause_drug_effects_MeSH S_physiology_MeSH Premenopause_physiology_MeSH M_Rest_MeSH 
****** 11006499
----K I
----T Effects of estrogen therapy on well-being in postmenopausal women without vasomotor complaints.
----A OBJECTIVE: To establish whether estrogen treatment affects well-being in postmenopausal women without current or previous vasomotor symptoms. Design: Forty postmenopausal women, aged 45-59 years, without current or previous vasomotor complaints, were included. They were randomized to masked treatment with either transdermal 17beta-estradiol 50 microg/24 h or to placebo. At baseline and after 12 and 14 weeks of treatment, the women completed a questionnaire which reflects well-being, the Psychological General Well-Being (PGWB) Index. Results: The women scored high on the PGWB Index, both at baseline and after 12 and 14 weeks of treatment. There was no significant difference in well-being according to PGWB Index between the groups treated with estrogen and placebo, neither at baseline, nor after therapy. Furthermore, there was no difference in change during therapy between the treatment groups. Conclusion: There is a gradual decline in estrogen during the climacteric, and it is controversial to which extent this affects women's mental health. The PGWB scores in this study were high before therapy, reflecting that these women without previous or current vasomotor complaints represented a selected sample. Neither short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone acetate during 2 weeks improved well-being in postmenopausal women without vasomotor symptoms who had high well-being at baseline.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH P_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11042235
----K E
----T The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial.
----A PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Analysis_of_Variance_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Catecholamines_MeSH S_blood_MeSH Catecholamines_blood_MeSH M_Cross-Over_Studies_MeSH M_Epinephrine_MeSH S_blood_MeSH Epinephrine_blood_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Female_MeSH M_Heart_Rate_MeSH S_drug_effects_MeSH Heart_Rate_drug_effects_MeSH M_Human_MeSH M_Mathematics_MeSH M_Middle_Aged_MeSH M_Norepinephrine_MeSH S_blood_MeSH Norepinephrine_blood_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH M_Stress__Psychological_MeSH S_prevention_&_control_MeSH Stress__Psychological_prevention_&_control_MeSH 
****** 11063900
----K I
----T Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.
----A OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Age_Factors_MeSH M_Body_Mass_Index_MeSH M_Bone_Density_MeSH M_Cohort_Studies_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Forearm_Injuries_MeSH S_epidemiology_MeSH Forearm_Injuries_epidemiology_MeSH S_prevention_&_control_MeSH Forearm_Injuries_prevention_&_control_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_epidemiology_MeSH Osteoporosis__Postmenopausal_epidemiology_MeSH S_therapy_MeSH Osteoporosis__Postmenopausal_therapy_MeSH M_Patient_Compliance_MeSH M_Postmenopause_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Regression_Analysis_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11063905
----K E
----T The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study.
----A OBJECTIVE: Several studies have shown a positive effect of oestrogen on memory, mood and well-being but these data are controversial and focus particularly on the effect of oestrogen alone. In this pilot study we have investigated the effect of a continuous combination of norethisterone acetate 1 mg and oestradiol valerate 2 mg (Kliogest) versus tibolone (Livial) on memory, sexuality and mood. METHODS: Twenty-two postmenopausal women, age range 51-57, were randomised to a 6 months single blind interventional study treatment with either continuous combined oestradiol plus norethisterone acetate, or tibolone. Computerised psychological test of memory, mood and libido were administered both before and at the end of the 6 months treatment. RESULTS: Fourteen patients completed the study; eight on Livial and six on Kliogest. Recognition memory was improved by Kliogest but not by Livial (P<0.05) while either drug equally improved both the reaction time (P<0.01) and accuracy of performance (P<0.001) of categorical semantic memory. Both the treatments improved libido significantly (P<0.05), while the mood did not change with either. CONCLUSION: The results suggest that both these forms of hormonal replacement therapy improve the efficiency of memory performance and libido. However, a combination of oestradiol and norethisterone acetate seems to be marginally more effective on improving cognitive processes.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Anabolic_Agents_MeSH S_pharmacology_MeSH Anabolic_Agents_pharmacology_MeSH S_therapeutic_use_MeSH Anabolic_Agents_therapeutic_use_MeSH M_Body_Mass_Index_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Libido_MeSH S_drug_effects_MeSH Libido_drug_effects_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Norpregnenes_MeSH S_pharmacology_MeSH Norpregnenes_pharmacology_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Patient_Compliance_MeSH M_Pilot_Projects_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH 
****** 11084176
----K E
----T Randomized comparison of intranasal and transdermal estradiol.
----A OBJECTIVE: To compare the efficacy and patient acceptability of intranasal versus transdermal 17 beta-estradiol (E2) delivery systems for postmenopausal symptoms. METHODS: Postmenopausal women were randomly assigned to intranasal 17 beta-E2, 300 microg daily (n = 176) or transdermal 17 beta-E2 (delivering 50 microg/day), two patches per week (n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. RESULTS: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups (P <.001). The difference between groups in the Kupperman Index score of -0.5 +/- 0.9 (95% confidence interval -2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P =.02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy (P <.001). Satisfaction was greater with intranasal therapy at week 16 (P <.001). CONCLUSION: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients' choice for long-term treatment.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Intranasal_MeSH M_Adult_MeSH M_Aged_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Patient_Acceptance_of_Health_Care_MeSH M_Treatment_Outcome_MeSH 
****** 11084177
----K E
----T Triphasic norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding.
----A OBJECTIVE: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol (E2) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). METHODS: In this multicenter, randomized, double-masked study, 201 women (15-50 years of age) with DUB received triphasic norgestimate-ethinyl E2 or placebo, for three consecutive 28-day treatment cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in subjects' quality of life. The sample size was based on the assumption that the proportions of subjects exhibiting treatment success (percentage of subjects with investigator and subject overall assessments of DUB resolution of "improved") were 65% for the active group and 40% for the placebo group (alpha = 0.05, 1 - beta = 0.80). RESULTS: More than 80% of subjects receiving triphasic norgestimate-ethinyl E2 had improvements in their abnormal bleeding patterns as assessed by investigators, and the subjects themselves compared with fewer than 50% of subjects in the placebo treatment group (P <.001). Abnormal bleeding patterns were reported by significantly fewer subjects receiving triphasic norgestimate-ethinyl E2 than in the placebo treatment group (P <. 001). Change from baseline in physical functioning (eg, self-care, walking, lifting, exercising) was significantly more improved in the triphasic norgestimate-ethinyl E2 group than in the placebo group. CONCLUSION: The triphasic combination of norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Contraceptives__Oral__Synthetic_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Synthetic_administration_&_dosage_MeSH S_adverse_effects_MeSH Contraceptives__Oral__Synthetic_adverse_effects_MeSH M_Double-Blind_Method_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Menstruation_Disturbances_MeSH S_drug_therapy_MeSH Menstruation_Disturbances_drug_therapy_MeSH M_Middle_Aged_MeSH M_Norgestrel_MeSH S_administration_&_dosage_MeSH Norgestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Norgestrel_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norgestrel_analogs_&_derivatives_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 11099873
----K E
----T The effect of estrogen replacement therapy on cardiac autonomic regulation.
----A OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Autonomic_Nervous_System_MeSH S_drug_effects_MeSH Autonomic_Nervous_System_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Heart_Rate_MeSH S_drug_effects_MeSH Heart_Rate_drug_effects_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Polysomnography_MeSH P_Postmenopause_MeSH M_Sleep_MeSH S_drug_effects_MeSH Sleep_drug_effects_MeSH 
****** 11109313
----K E
----T [Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension]
----A AIM: The effect of hormone replacement therapy (HRT) on the quality of life in women with hypertension is still not clear. Thus, the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of standardized questionnaires. MATERIAL AND METHODS: The study population consisted of 53 women (mean age 50.9 +/- 6.3 years) with mild and moderate essential hypertension (mean duration 6.4 +/- 6.4 years). The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml, accompanied by follicle-stimulating hormone (FSH) levels > 21 U/I. Twenty seven women were blindly randomised to transdermal hormone replacement therapy (HRT) and received 17-beta-estradiol and noretisterone acetate, TTS. Twenty six women were randomly selected as controls. The subjects were evaluated at baseline (after 2 weeks' wash-out from hypotensive drug period) and after three months of HRT using self-administered standardized quality of life questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptoms Assessment Profile (SSA-P). RESULTS: No differences were found in blood pressure values, heart rate, body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up. There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups. Similarly, the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline. After 3 months, a significant improvement in PGWB total score was observed in women receiving HRT. This effect was due to improvement in anxiety, positive well-being and vitality. Moreover, emotional distress, symptoms of flushing, sweating and trembling hands also diminished and sexual capacity improved in women treated with HRT. CONCLUSION: A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being, seems to decrease emotional tension, increase sexual capacity and markedly relieves some vasomotor symptoms.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adipose_Tissue_MeSH S_drug_effects_MeSH Adipose_Tissue_drug_effects_MeSH M_Body_Mass_Index_MeSH M_Drug_Combinations_MeSH M_Drug_Therapy__Combination_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hemodynamic_Processes_MeSH S_drug_effects_MeSH Hemodynamic_Processes_drug_effects_MeSH M_Human_MeSH M_Hypertension_MeSH S_complications_MeSH Hypertension_complications_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH 
****** 11137327
----K E
----T Efficacy and tolerability of fully transdermal hormone replacement in sequential or continuous therapy at two doses of progestogen in postmenopausal women.
----A OBJECTIVES: Two randomized open-label studies were performed to evaluate fully transdermal hormone replacement therapy (HRT) with oestradiol (E2) and norethisterone acetate (NETA) in postmenopausal women. METHODS: Both hormones were delivered by transdermal matrix patches changed twice weekly. Subjects received E2, 50 microg/day and NETA, 170 microg/day or 350 microg/day, either continuously or sequentially. A one-year study (13 cycles of 28 days), including a reference regimen of transdermal E2 and sequential oral progestogen, was followed by a continuation study for a further year in 367 women. RESULTS: All regimens were highly and equally effective in the prevention of hot flushes. The fully transdermal regimens were associated with beneficial changes in the lipid profile. The sequential regimens provided effective scheduling of bleeding around the end of the progestogen phase. The continuous regimens were associated with irregular bleeding, which was rarely severe, and a gradually increasing incidence of amenorrhoea. With sequential or continuous therapy, bleeding was less severe at the lower dose of progestogen than at the higher dose. No endometrial hyperplasia was detected by biopsy in any treatment group. One serous endometrial carcinoma and one endometrial adenocarcinoma were detected. An endometrial thickness >5 mm did not predict the presence of hyperplasia at biopsy. Hormone-related adverse events were typical of those expected for HRT and dermal tolerability of the patches was good. CONCLUSIONS: Fully transdermal sequential or continuous HRT is effective and well tolerated in postmenopausal women. The lower dose of NETA may be preferable, because it confers adequate endometrial protection at a lower dose of progestogen.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Drug_Combinations_MeSH M_Drug_Therapy__Combination_MeSH M_Endometrial_Hyperplasia_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Risk_Factors_MeSH M_Treatment_Outcome_MeSH 
****** 11127760
----K E
----T The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (femhrt) on the frequency and intensity of vasomotor symptoms.
----A OBJECTIVE: To determine whether there is a significant reduction in frequency and severity of hot flashes in symptomatic postmenopausal women who are administered continuously different dose combinations of norethindrone acetate and ethinyl estradiol. DESIGN: Two randomized clinical trials (Study 1 and Study 2) were conducted in which study participants recorded in daily diaries the frequency of their hot flashes. Study 2 participants also recorded the number of mild, moderate, or severe hot flashes they experienced. In Study 1, a total of 219 postmenopausal women reporting vasomotor symptoms were placed randomly into groups to receive either a placebo or 1 of 4 treatments (0.2 mg/1 microg; 0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate/ethinyl estradiol). In Study 2, a total of 266 highly symptomatic postmenopausal women were placed randomly to receive either a placebo or 1 of 3 treatment groups [0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate (NA)/ethinyl estradiol (EE)]. Total duration of treatment was 16 weeks in Study 1 and 12 weeks in Study 2. Study 1 subjects had to have at least 10 hot flashes during the week before randomization. Study 2 subjects had to have at least 56 moderate to severe hot flashes during the week before randomization. RESULTS: In both studies, there was a dose-related decrease in hot flash frequency with the highest dose (1 mg NA/10 microg EE) group that had the greatest response. Significant differences from placebo (p < 0.05, Dunnett's test) occurred within 4 weeks in Study 1 for hot flash frequency with a percent reduction in frequency ranging from 33% for placebo to 84% for both the 1 mg NA/10 microg EE and 1 mg NA/5 microg EE dose groups. Likewise, Study 2 significant reductions in hot flash frequency occurred by Week 2 for 1 mg NA/10 microg EE, Week 3 for 1 mg NA/5 microg EE, and Week 5 for 0.5 mg NA/2.5 microg EE (p < 0.05, Dunnett's test). This dose effect was also apparent with regard to severity. In addition, more subjects had clinically meaningful reductions in hot flash frequency or elimination as the dose combinations increased. CONCLUSION: There were significant reductions in hot flash frequency and severity with continuous treatment with norethindrone acetate and ethinyl estradiol combinations. The time at which significant reductions were observed, as well as the magnitude of the response, were dose dependent. The opportunity for lower-dose options of a new continuous-combined hormone replacement therapy provides therapeutic flexibility for women who are recently menopausal.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Oregon_MeSH M_Postmenopause_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11152919
----K I
----T Postmenopausal hormones and incontinence: the Heart and Estrogen/Progestin Replacement Study.
----A OBJECTIVE: To determine whether postmenopausal hormone therapy improves the severity of urinary incontinence. METHODS: We included measures of incontinence and voiding frequency in the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effect of hormone therapy among 2763 postmenopausal women younger than 80 years with coronary disease and intact uteri. This report includes 1525 participants who reported at least one episode of incontinence per week at baseline. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate in one tablet daily (n = 768) or placebo (n = 757) and were followed for a mean of 4.1 years. Severity of incontinence was classified as improved (decrease of at least two episodes per week), unchanged (change of at most one episode per week), or worsened (increase of at least two episodes per week). RESULTS: Incontinence improved in 26% of the women assigned to placebo compared with 21% assigned to hormones, while 27% of the placebo group worsened compared with 39% of the hormone group (P =.001). This difference was evident by 4 months of treatment and was observed for both urge and stress incontinence. The number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P <.001). CONCLUSION: Daily oral estrogen plus progestin therapy was associated with worsening urinary incontinence in older postmenopausal women with weekly incontinence. We do not recommend this therapy for the treatment of incontinence.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Drug_Combinations_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Randomized_Controlled_Trials_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Failure_MeSH M_Urinary_Incontinence_MeSH S_drug_therapy_MeSH Urinary_Incontinence_drug_therapy_MeSH S_prevention_&_control_MeSH Urinary_Incontinence_prevention_&_control_MeSH M_Urinary_Incontinence__Stress_MeSH S_drug_therapy_MeSH Urinary_Incontinence__Stress_drug_therapy_MeSH S_prevention_&_control_MeSH Urinary_Incontinence__Stress_prevention_&_control_MeSH 
****** 11173778
----K E
----T Acute effects of transdermal estrogen in postmenopausal women with coronary artery disease. Using a clinically relevant estrogen dose and concurrent antianginal therapy.
----A In the present study the acute anti-ischemic effect of clinically relevant doses of transdermal estradiol during concurrent antianginal therapy was investigated in 14 postmenopausal women with stable coronary artery disease. Plasma estradiol was significantly increased, but no significant effects on time to angina, time to 1 mm S--T depression, total exercise time, maximum rate-pressure product, maximum S--T depression or maximum workload were found. However, resting diastolic blood pressure was significantly decreased due to estrogen.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Angina_Pectoris_MeSH S_drug_therapy_MeSH Angina_Pectoris_drug_therapy_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_drug_therapy_MeSH Myocardial_Ischemia_drug_therapy_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11158017
----K E
----T Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause.
----A The psychological symptoms assessed with a validated psychometric scale, SCL-90, were significantly higher in postmenopausal women (PMW; 60 subjects) than in premenopausal women (20 subjects). In the same PMW, the activity of the dopaminergic system, assessed with the PRL response to the dopamine-blocking agent sulpiride, was significantly lower than that in premenopausal women. During a period of 12 weeks the 60 PMW were randomly divided into 3 groups: no treatment (group A; n = 20), treatment with estradiol (E(2)) alone (patches with a E(2) release of 50 microg/24 h; group B; n = 20), and treatment with hormonal replacement therapy [estradiol valerate (EV) at a daily dose of 2 mg for 11 days and EV at the same daily doses plus cyproterone acetate (CPA) at a daily dose of 1 mg/day for 10 days; group C; n = 20). At the 12th week of the observation, only in group C women were the psychological symptoms significantly decreased, and the indirect evaluation of the dopaminergic system activity through PRL response to sulpiride showed a significant increase. During the same period, no changes in testosterone levels were observed in any group of PMW, whereas a significant increase in E(2) levels was found in both groups B and C. Although it is likely that the improvement in psychological symptoms with EV and CPA was due to progestin, we cannot rule out the possibility that greater estrogen exposure may have played a role.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Androgen_Antagonists_MeSH S_therapeutic_use_MeSH Androgen_Antagonists_therapeutic_use_MeSH M_Anxiety_MeSH M_Area_Under_Curve_MeSH M_Cyproterone_Acetate_MeSH S_therapeutic_use_MeSH Cyproterone_Acetate_therapeutic_use_MeSH M_Depression_MeSH M_Dopamine_MeSH S_physiology_MeSH Dopamine_physiology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Mental_Disorders_MeSH S_drug_therapy_MeSH Mental_Disorders_drug_therapy_MeSH S_etiology_MeSH Mental_Disorders_etiology_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH M_Premenopause_MeSH S_physiology_MeSH Premenopause_physiology_MeSH S_psychology_MeSH Premenopause_psychology_MeSH M_Prolactin_MeSH S_blood_MeSH Prolactin_blood_MeSH S_secretion_MeSH Prolactin_secretion_MeSH M_Psychological_Tests_MeSH M_Psychometrics_MeSH M_Reproducibility_of_Results_MeSH M_Sulpiride_MeSH S_diagnostic_use_MeSH Sulpiride_diagnostic_use_MeSH 
****** 11226444
----K E
----T Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.
----A OBJECTIVE: To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women. METHODS: Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding. RESULTS: Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA. CONCLUSIONS: The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Norgestrel_MeSH S_administration_&_dosage_MeSH Norgestrel_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norgestrel_analogs_&_derivatives_MeSH M_Postmenopause_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH S_pharmacology_MeSH Progestins_pharmacology_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH 
****** 11255422
----K I
----T Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women.
----A CONTEXT: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. OBJECTIVES: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. DESIGN AND SETTING: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. PARTICIPANTS: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. MAIN OUTCOME MEASURE: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). RESULTS: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17). CONCLUSIONS: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.
----P Journal_Article 
----M M_Aged_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_statistics_&_numerical_data_MeSH Estrogen_Replacement_Therapy_statistics_&_numerical_data_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Ovarian_Neoplasms_MeSH S_epidemiology_MeSH Ovarian_Neoplasms_epidemiology_MeSH S_mortality_MeSH Ovarian_Neoplasms_mortality_MeSH M_Ovary_MeSH S_drug_effects_MeSH Ovary_drug_effects_MeSH M_Postmenopause_MeSH M_Proportional_Hazards_Models_MeSH M_Prospective_Studies_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH M_Time_Factors_MeSH 
****** 11275026
----K E
----T Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial.
----A OBJECTIVE: To evaluate the effect of estrogen replacement therapy on nocturnal periodic limb movements in a randomized, double-masked, placebo-controlled, crossover trial. METHODS: Seventy-one healthy postmenopausal women volunteered in answer to a newspaper announcement; 62 women completed the follow-up. Frequency of nocturnal body movements was measured with the static-charge-sensitive bed and all-night polysomnographic recordings. Serum estradiol (E2) and FSH concentrations were also measured at baseline and after each treatment period. The power of the study setup was 94%. RESULTS: Nearly half the women presented with episodes of periodic limb movements (30 of 62 women, or 48%, during placebo and 27, or 44%, during estrogen therapy). In 17 (27%) during placebo and 19 (31%) during estrogen therapy, frequency of periodic limb movements exceeded index level 5 per hour while subjects were in bed. Incidence or intensity of movements, movement durations, and movement intervals did not change with estrogen therapy. The arousal index was similar during the two treatments (medians = 1.7 for placebo and 1.3 for estrogen, P =.758). Variations in serum E2 concentration, age, and body mass index did not explain variations in movement activity. CONCLUSION: Estrogen replacement therapy in doses used to control climacteric symptoms does not alter the incidence or intensity of nocturnal periodic limb movements.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Arm_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Dyskinesias_MeSH S_etiology_MeSH Dyskinesias_etiology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Leg_MeSH M_Middle_Aged_MeSH M_Polysomnography_MeSH M_Sleep_Disorders_MeSH S_chemically_induced_MeSH Sleep_Disorders_chemically_induced_MeSH 
****** 11304880
----K E
----T Effects of estrogen/androgen therapy on bone mineral density parameters.
----A Although estrogen's efficacy in reversing loss of bone mineral density (BMD) has been extensively documented, the role of androgens in preserving and restoring BMD is less well understood. Estrogen/androgen (E/A) therapy is especially important for surgically menopausal women. This population group experiences marked bone loss in response to the dramatic decline in ovarian hormones. The resulting hormonal profile differs significantly from that of naturally menopausal women. For surgically menopausal women, the relation of estrogens, androgens and sex hormone binding globulin (SHBG) is of special concern, as the interrelation between these hormones ultimately may reduce hormonal bioavailability. This paper reviews the relation of bone metabolism to ovarian hormones and the mechanics of BMD loss as well as the tools available to clinicians to assess bone loss in menopausal women. It further discusses androgen excess in women with polycystic ovary syndrome. Currently available hormonal regimens to preserve bone are described, including estrogen-only therapy, E/A therapy, tibolone and estrogen-progestogen therapy.
----P Journal_Article Review Review__Tutorial 
----M M_Androgens_MeSH S_therapeutic_use_MeSH Androgens_therapeutic_use_MeSH P_Bone_Density_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Hyperandrogenism_MeSH P_Menopause_MeSH M_Menopause__Premature_MeSH M_Osteoporosis__Postmenopausal_MeSH S_etiology_MeSH Osteoporosis__Postmenopausal_etiology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Ovariectomy_MeSH S_adverse_effects_MeSH Ovariectomy_adverse_effects_MeSH M_Polycystic_Ovary_Syndrome_MeSH S_complications_MeSH Polycystic_Ovary_Syndrome_complications_MeSH 
****** 11304940
----K E
----T Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.
----A The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Arousal_MeSH S_drug_effects_MeSH Arousal_drug_effects_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Electroencephalography_MeSH S_drug_effects_MeSH Electroencephalography_drug_effects_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Evoked_Potentials_MeSH S_drug_effects_MeSH Evoked_Potentials_drug_effects_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Nandrolone_MeSH S_analogs_&_derivatives_MeSH Nandrolone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Nandrolone_pharmacology_MeSH M_Personality_MeSH S_drug_effects_MeSH Personality_drug_effects_MeSH M_Progestins_MeSH S_pharmacology_MeSH Progestins_pharmacology_MeSH M_Psychometrics_MeSH M_Psychomotor_Performance_MeSH S_drug_effects_MeSH Psychomotor_Performance_drug_effects_MeSH M_Pupil_MeSH S_drug_effects_MeSH Pupil_drug_effects_MeSH M_Sleep_MeSH S_drug_effects_MeSH Sleep_drug_effects_MeSH 
****** 11306204
----K E
----T Course of primary headaches during hormone replacement therapy.
----A OBJECTIVE: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. METHODS: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001). CONCLUSIONS: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Common_Migraine_MeSH S_metabolism_MeSH Common_Migraine_metabolism_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH S_pharmacology_MeSH Medroxyprogesterone_pharmacology_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Prospective_Studies_MeSH M_Severity_of_Illness_Index_MeSH M_Tension_Headache_MeSH S_metabolism_MeSH Tension_Headache_metabolism_MeSH M_Treatment_Outcome_MeSH 
****** 11336741
----K I
----T Modification of vasomotor symptoms after various treatment modalities in the postmenopause.
----A 
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Clonidine_MeSH S_therapeutic_use_MeSH Clonidine_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Propranolol_MeSH S_therapeutic_use_MeSH Propranolol_therapeutic_use_MeSH M_Sulpiride_MeSH S_analogs_&_derivatives_MeSH Sulpiride_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Sulpiride_therapeutic_use_MeSH M_Treatment_Outcome_MeSH M_Vasodilator_Agents_MeSH S_therapeutic_use_MeSH Vasodilator_Agents_therapeutic_use_MeSH 
****** 11386980
----K I
----T Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial.
----A BACKGROUND: Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17beta-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women. METHODS: Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17beta-estradiol (100 microgram) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores. RESULTS: Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17beta-estradiol compared with 5 (20%) in the placebo group (P =.001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups. CONCLUSION: Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Depression_MeSH S_diagnosis_MeSH Depression_diagnosis_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH S_psychology_MeSH Depression_psychology_MeSH M_Depressive_Disorder_MeSH S_diagnosis_MeSH Depressive_Disorder_diagnosis_MeSH S_drug_therapy_MeSH Depressive_Disorder_drug_therapy_MeSH S_psychology_MeSH Depressive_Disorder_psychology_MeSH M_Double-Blind_Method_MeSH M_Dysthymic_Disorder_MeSH S_diagnosis_MeSH Dysthymic_Disorder_diagnosis_MeSH S_drug_therapy_MeSH Dysthymic_Disorder_drug_therapy_MeSH S_psychology_MeSH Dysthymic_Disorder_psychology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Menopause_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH M_Psychiatric_Status_Rating_Scales_MeSH S_statistics_&_numerical_data_MeSH Psychiatric_Status_Rating_Scales_statistics_&_numerical_data_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 11398578
----K E
----T [The effect of hormonal replacement therapy on symptoms of climacteric syndrome and selected metabolic parameters]
----A GOAL OF STUDY: The goal of this paper was estimation of influence of HRT (after 3 and 6 months of treatment of 112 women) the symptoms of climacteric syndrome and depression associated with the said syndrome based on the scales of Kupperman, Green, Hamilton and Beck as well as some selected parameters of metabolic state--concentration of foloculotropic hormonal profile FSH and 17 beta-estradiol E2, lipid profile (TC, HDL, LDL, TG-A) and glucose concentration. CONCLUSIONS: 1. The implementation of hormonal replacement therapy on 112 women made it possible to conclude that the treatment caused withdrawal of symptoms of climacteric syndrome and depression associated with the said syndrome. 2. Hormonal Replacement Therapy to a great extent had a beneficial influence on the lipid profile with 112 women after menopause especially as far as LDL is concerned. 3. HRT caused enormously significant increase in 17 beta-estradiol concentration and decrease of FSH concentration. 4. HRT statistically had no impact on glucose level with the study group of women.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Aged_MeSH M_Blood_Glucose_MeSH S_metabolism_MeSH Blood_Glucose_metabolism_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH S_metabolism_MeSH Climacteric_metabolism_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_analysis_MeSH Estradiol_analysis_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_analysis_MeSH Follicle_Stimulating_Hormone_analysis_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Hysterectomy_MeSH M_Lipids_MeSH S_metabolism_MeSH Lipids_metabolism_MeSH M_Lipoproteins__LDL_MeSH S_analysis_MeSH Lipoproteins__LDL_analysis_MeSH M_Middle_Aged_MeSH 
****** 11403976
----K E
----T Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls.
----A BACKGROUND: GABA receptor-modifying neurosteroids may play a role in premenstrual syndrome (PMS). The peripheral benzodiazepine receptor (PBR) both regulates the formation of neurosteroids and is, in animals, regulated by ovarian steroids. Alterations in PBR density have been observed in association with several psychiatric disorders. METHODS: We examined the effects of gonadal steroids on lymphocytic PBR density in nine women with prospectively confirmed PMS and nine controls. PBR densities were measured during three pharmacologically controlled conditions: gonadotropin releasing hormone agonist (Lupron)-induced hypogonadism, Lupron plus estradiol, and Lupron plus progesterone replacement. Blood samples were obtained after six weeks of Lupron alone and after 3-4 weeks of estradiol and progesterone replacement. RESULTS: No significant hormone state-related changes in PBR density were observed (ANOVA-R: phase-F(2,32)=1.5, P=0.2). Despite mood symptom development in the subjects with PMS, PBR density did not differ in women with PMS compared to controls across hormonal states (ANOVA-R: F(1,16)=0.6, P=0.4). CONCLUSIONS: PBR densities are not altered in women with PMS and are not changed significantly by selective gonadal steroid administration. Changes in PBR density would not appear to underlie the differential sensitivity to the mood destabilizing effects of ovarian steroids in PMS.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Leuprolide_MeSH S_pharmacology_MeSH Leuprolide_pharmacology_MeSH M_Lymphocytes_MeSH S_metabolism_MeSH Lymphocytes_metabolism_MeSH M_Premenstrual_Syndrome_MeSH S_blood_MeSH Premenstrual_Syndrome_blood_MeSH M_Progesterone_MeSH S_pharmacology_MeSH Progesterone_pharmacology_MeSH M_Receptors__GABA-A_MeSH S_blood_MeSH Receptors__GABA-A_blood_MeSH S_drug_effects_MeSH Receptors__GABA-A_drug_effects_MeSH 
****** 11408508
----K E
----T Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants.
----A PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH S_etiology_MeSH Breast_Neoplasms_etiology_MeSH S_prevention_&_control_MeSH Breast_Neoplasms_prevention_&_control_MeSH M_Double-Blind_Method_MeSH P_Estrogens_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH S_metabolism_MeSH Estrogens_metabolism_MeSH S_physiology_MeSH Estrogens_physiology_MeSH M_Female_MeSH M_Human_MeSH M_Incidence_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH M_Postmenopause_MeSH M_Raloxifene_MeSH S_pharmacology_MeSH Raloxifene_pharmacology_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Risk_MeSH M_Risk_Factors_MeSH M_Selective_Estrogen_Receptor_Modulators_MeSH S_pharmacology_MeSH Selective_Estrogen_Receptor_Modulators_pharmacology_MeSH S_therapeutic_use_MeSH Selective_Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 11408781
----K E
----T Sensitivity to a neurosteroid is increased during addition of progestagen to postmenopausal hormone replacement therapy.
----A The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT). Twenty-seven postmenopausal women with climacteric symptoms were administered HRT in a randomized, double-blinded, placebo-controlled crossover study. The women received 2 mg estradiol (E2) continuously during four 28-day cycles and 10 mg medroxyprogesterone acetate (MPA), 1 mg norethisterone acetate (NETA) or placebo sequentially for the last 14 days in each cycle. The pharmacodynamic response to pregnanolone was assessed before treatment and during the last week of each treatment, by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV), saccade deceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. During the progesta gen phase of the treatment cycles, negative mood symptoms and physical symptoms were increased, whereas positive mood symptoms were decreased. Compared to pretretreatment conditions, E2 alone did not change the responsiveness to pregnanolone. During progestagen addition to E2, the responsiveness to pregnanolone was increased. The sedation response increased compared to pretreatment conditions during both E2 + MPA and E2 + NETA treatment. Compared to E2 treatment alone, addition of MPA increased the postpregnanolone effect on saccade deceleration, whereas the SEV response to pregnanolone was increased during E2 + NETA treatment. It is concluded that pregnanolone sensitivity increases together with deterioration in mood symptoms during addition of progestagen to HRT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Climacteric_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Placebos_MeSH P_Postmenopause_MeSH M_Pregnanolone_MeSH S_blood_MeSH Pregnanolone_blood_MeSH S_pharmacology_MeSH Pregnanolone_pharmacology_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH S_adverse_effects_MeSH Progestins_adverse_effects_MeSH M_Saccades_MeSH S_drug_effects_MeSH Saccades_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11420773
----K I
----T The prevention of osteoporosis using sequential low-dose hormone replacement therapy with estradiol-17 beta and dydrogesterone.
----A Low-dose hormone replacement therapy (HRT) in postmenopausal women may produce fewer side-effects but its efficacy in the prevention of bone loss and osteoporosis is not established. To address this we compared the effect of 1 mg estradiol-17 beta with a 2 mg dose, in combination with cyclical dydrogesterone, in the prevention of postmenopausal bone loss. We conducted a multicenter double-masked prospective randomized, placebo-controlled study in 595 apparently healthy postmenopausal women randomized to either placebo, or continuous oral estradiol-17 beta 1 mg or 2 mg with sequential dydrogesterone for 2 years. The primary endpoint was the percentage change from baseline in bone mineral density (BMD) in the lumbar spine (LS) and femoral neck (FN) of actively treated groups compared with placebo. Women taking either 1 mg or 2 mg estradiol-17 beta showed a significant increase in BMD of the LS (mean +/- SD, 5.2 +/- 3.8% and 6.7 +/- 4.0% respectively, both p < 0.001) whilst BMD in the placebo group decreased (-1.9 +/- 4.0%). Increases were also observed in FN BMD in both treated groups (2.7 +/- 4.2% and 2.5 +/- 5.2% respectively, both p < 0.001) in contrast to the placebo group (-1.8 +/- 4.8%). The oldest women showed the greatest treatment response. One milligram estradiol-17 beta in combination with dydrogesterone is effective in conserving LS and proximal femur bone mass, both of which are clinically important sites of osteoporotic fracture, and is as effective as 2 mg in preventing FN bone. The lower dose of estradiol-17 beta is a particularly suitable treatment for osteoporosis management in older women since it should minimize side-effects and improve the acceptability of HRT.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Aging_MeSH S_physiology_MeSH Aging_physiology_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Combinations_MeSH M_Dydrogesterone_MeSH S_administration_&_dosage_MeSH Dydrogesterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Dydrogesterone_therapeutic_use_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Time_Factors_MeSH 
****** 11428178
----K E
----T Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women.
----A OBJECTIVES: Many women seek alternatives to hormonal therapies for the management of menopausal symptoms. Among the treatments currently popular are extracts of wild yam (Dioscorea villosa), which are applied topically in the form of a cream. These preparations are known to contain steroidal saponins, including diosgenin, which has been claimed to influence endogenous steroidogenesis. However, there have been no studies of the safety or efficacy of these preparations in the management of menopausal symptoms. METHODS: We therefore conducted a double-blind, placebo-controlled, cross-over study of the effects of a wild yam cream in 23 healthy women suffering from troublesome symptoms of the menopause. After a 4-week baseline period, each woman was given active cream and matching placebo for 3 months in random order. Diaries were completed over the baseline period and for 1 week each month thereafter, and blood and saliva samples were collected at baseline and at 3 and 6 months, for measurement of lipids and hormones. RESULTS: The average age of the subjects was 53.3 +/- 1.1 (SEM) years and average time since last period 4.3 +/- 0.9 years. At baseline, the average body mass index was 27.3 +/- 0.8, cholesterol level 5.7 +/- 0.2 mmol/l and follicle stimulating hormone (FSH) level 74.2 +/- 5.1 IU/l; estradiol levels were undetectable in the majority of cases. After 3 months of treatment, no significant side-effects were reported with either active treatment or placebo, and there were no changes in weight, systolic or diastolic blood pressure, or levels of total serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, FSH, glucose, estradiol, or serum or salivary progesterone. Symptom scores showed a minor effect of both placebo and active treatment on diurnal flushing number and severity and total non-flushing symptom scores, and on nocturnal sweating after placebo, but no statistical difference between placebo and active creams. CONCLUSIONS: This study suggests that short-term treatment with topical wild yam extract in women suffering from menopausal symptoms is free of side-effects, but appears to have little effect on menopausal symptoms. It emphasizes the importance of careful study of treatments for menopausal symptoms if women are to be adequately informed about the choices available to them.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Blood_Glucose_MeSH S_metabolism_MeSH Blood_Glucose_metabolism_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH P_Liliaceae_MeSH M_Lipids_MeSH S_metabolism_MeSH Lipids_metabolism_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH P_Phytotherapy_MeSH M_Plant_Extracts_MeSH S_administration_&_dosage_MeSH Plant_Extracts_administration_&_dosage_MeSH S_therapeutic_use_MeSH Plant_Extracts_therapeutic_use_MeSH M_Progesterone_MeSH S_metabolism_MeSH Progesterone_metabolism_MeSH M_Reference_Values_MeSH M_Support__Non-U_S__Gov't_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 11445632
----K E
----T Testosterone supplementation improves spatial and verbal memory in healthy older men.
----A OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition. METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests. RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures. CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Human_MeSH M_Injections__Intramuscular_MeSH P_Language_MeSH M_Male_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH M_Neuropsychological_Tests_MeSH M_Reference_Values_MeSH M_Space_Perception_MeSH S_physiology_MeSH Space_Perception_physiology_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_analogs_&_derivatives_MeSH Testosterone_analogs_&_derivatives_MeSH S_blood_MeSH Testosterone_blood_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH 
****** 11449079
----K E
----T Esterified estrogens combined with methyltestosterone improve emotional well-being in postmenopausal women with chest pain and normal coronary angiograms.
----A OBJECTIVE: The cardiac syndrome X is described as the triad of angina pectoris, a positive exercise test for myocardial ischemia, and angiographically smooth coronary arteries. Although syndrome X does not result in an increased risk of cardiovascular mortality, the symptoms are often troublesome and unresponsive to conventional antianginal therapy. The majority of patients are postmenopausal, and estrogen therapy can alleviate anginal symptoms. We investigated the effect of esterified estrogens combined with methyltestosterone (Estratest) on quality of life in postmenopausal women with syndrome X. DESIGN: Patients were withdrawn from antianginal therapy. Sublingual nitrates were allowed for treatment of anginal episodes. Patients underwent treadmill testing, and quality of life was assessed by using the Short Form-36 and Cardiac Health Profile questionnaires after the women had received 8 weeks of Estratest or identical placebo in a randomized, double-blind, cross-over study. RESULTS: Nineteen patients were randomized, and 16 patients completed the protocol. Plasma 17beta-estradiol concentrations were significantly increased by Estratest; however, total testosterone levels were not. The "emotional" score of the Cardiac Health Profile questionnaire was significantly improved after Estratest use compared with placebo (p = 0.03); however, there was no significant change in the Short Form-36 questionnaire for any variable. Estratest significantly increased systolic blood pressure and rate pressure product at rest but had no effect on exercise parameters. Time to onset of chest pain during exercise was also unaffected. CONCLUSIONS: We have demonstrated a beneficial effect of Estratest on emotional well-being in postmenopausal women with cardiological syndrome X. There was no significant treatment effect on exercise parameters, including time to onset of chest pain.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Drug_Monitoring_MeSH M_Emotions_MeSH S_drug_effects_MeSH Emotions_drug_effects_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH S_standards_MeSH Estrogen_Replacement_Therapy_standards_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Exercise_Test_MeSH S_drug_effects_MeSH Exercise_Test_drug_effects_MeSH M_Female_MeSH M_Human_MeSH M_Mental_Health_MeSH M_Methyltestosterone_MeSH S_pharmacology_MeSH Methyltestosterone_pharmacology_MeSH S_therapeutic_use_MeSH Methyltestosterone_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH M_Prospective_Studies_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH M_Syndrome_X_MeSH S_blood_MeSH Syndrome_X_blood_MeSH S_diagnosis_MeSH Syndrome_X_diagnosis_MeSH S_drug_therapy_MeSH Syndrome_X_drug_therapy_MeSH S_etiology_MeSH Syndrome_X_etiology_MeSH S_psychology_MeSH Syndrome_X_psychology_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH M_Treatment_Outcome_MeSH 
****** 11449087
----K E
----T A scheme of combined oral contraceptives for women more than 40 years old.
----A OBJECTIVE: To study whether the addition of estrogen to the 7 hormone-free days of a combined oral contraceptive (OC) cycle improves the symptomatology in perimenopausal women with climacteric complaints. DESIGN: A total of 56 women in their forties presenting with mood disorders and/or hot flashes were included in this randomized double-blind study. Symptoms were evaluated using the Greene test. Subjects were allocated into two groups: 23 women received an OC containing 20 microg of ethinyl-estradiol and 150 mg of desogestrel for 21 days and then 7 placebo tablets (placebo group); the other 33 women received 21 tablets with the same hormone combination, followed by 2 placebo tablets and 5 ethinyl-estradiol tablets of 10 microg each (estrogen group). After three cycles, symptoms were reassessed. RESULTS: Symptoms were similar in the two groups at the start of the study. Three months later, vasomotor symptoms in the placebo group dropped from 3.3 +/- 1.7 to 1.7 +/- 1.8, and in the estrogen group, from 3.0 +/- 1.7 to 0.7 +/- 0.9 (p < 0.04). Similarly, symptoms of depression fell from 8.8 +/- 4.0 to 6.7 +/- 3.9 in the placebo group and from 10.3 +/- 3.5 to 3.8 +/- 2.9 in the estrogen group (p < 0.002). Somatic symptoms fell with placebo from 10.9 +/- 5.3 to 7.4 +/- 5.4, and with estrogen, from 9.7 +/- 4.9 to 4.0 +/- 2.5 (p < 0.03). Sexual dysfunction as measured by the Greene Scale (loss of sexual interest) also improved more in women who received additional estrogen: 2.0 +/- 0.9 to 0.5 +/- 0.9 vs. 1.8 +/- 1.2 to 1.2 +/- 1.2, p < 0.03. Anxiety symptoms improved in both groups but without any significant difference between them. CONCLUSIONS: Adding 5 days of estrogen to the classic contraceptive scheme improves the climacteric symptoms of perimenopausal women who use OCs.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Age_Factors_MeSH M_Anxiety_MeSH S_drug_therapy_MeSH Anxiety_drug_therapy_MeSH S_etiology_MeSH Anxiety_etiology_MeSH M_Comparative_Study_MeSH M_Contraceptives__Oral__Combined_MeSH S_pharmacology_MeSH Contraceptives__Oral__Combined_pharmacology_MeSH S_therapeutic_use_MeSH Contraceptives__Oral__Combined_therapeutic_use_MeSH M_Depression_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH S_etiology_MeSH Depression_etiology_MeSH M_Desogestrel_MeSH S_therapeutic_use_MeSH Desogestrel_therapeutic_use_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_Congeners_MeSH S_therapeutic_use_MeSH Estradiol_Congeners_therapeutic_use_MeSH M_Ethinyl_Estradiol_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Parity_MeSH S_drug_effects_MeSH Parity_drug_effects_MeSH M_Premenopause_MeSH S_drug_effects_MeSH Premenopause_drug_effects_MeSH S_physiology_MeSH Premenopause_physiology_MeSH S_psychology_MeSH Premenopause_psychology_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Sexual_Dysfunctions__Psychological_MeSH S_drug_therapy_MeSH Sexual_Dysfunctions__Psychological_drug_therapy_MeSH S_etiology_MeSH Sexual_Dysfunctions__Psychological_etiology_MeSH M_Treatment_Outcome_MeSH 
****** 11449182
----K E
----T Sexually and well-being in early menopause. Effect of transdermal estradiol therapy.
----A BACKGROUND: This study focus on the effect of 6 months transdermal estradiol therapy (TTS) on the sexual behaviour and the quality of life in early menopausal women, complaining of uncomfortable menopausal symptoms. METHODS: Three hundred and sixty-two postmenopausal women, aged 48-56, participated in this study. One hundred and seventy-one of them were given continuous solid matrix patch TTS 50 mg/day for 6 months. Sexual behaviour, menopausal symptoms and well-being were evaluated through a self-rating method. We used a structured questionnaire with three obligatory answers (less/same/more) for each question--sexual life, hot flushes, touchiness, insomnia, blood pressure, work willing, memory loss, well-being--filled in by the women themselves or by the medical equipe after a telephone interview. RESULTS: Seventy five per cent of women aged 51-53 and 84% aged 54-56, who had been treated for 6 months with TTS showed a fall of sexual drive, if compared with, respectively, 62% and 48% of untreated subjects. Relief of hot flushes, touchiness and insomnia occurred in 80% of treated women, with slight differences among the various groups while 61% showed increase of well-being. CONCLUSIONS: The results of our study demonstrate that continuous TTS for 6 months decreased sexual drive in 69% of women, improved menopausal symptoms in 80% women but increased well-being only in 61% of women. These differences suggest that women's well-being does not seem linked only to the relief of menopausal symptoms and the impairment of their sexual life can play a negative role.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH P_Health_Status_MeSH M_Human_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH P_Sexuality_MeSH S_drug_effects_MeSH Sexuality_drug_effects_MeSH M_Treatment_Outcome_MeSH 
****** 11400216
----K E
----T Physiology of hot flashes.
----A Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.
----P Journal_Article Review Review__Tutorial 
----M M_Body_Temperature_Regulation_MeSH S_physiology_MeSH Body_Temperature_Regulation_physiology_MeSH M_Circadian_Rhythm_MeSH M_Clonidine_MeSH S_pharmacology_MeSH Clonidine_pharmacology_MeSH S_therapeutic_use_MeSH Clonidine_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_diagnosis_MeSH Hot_Flashes_diagnosis_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_epidemiology_MeSH Hot_Flashes_epidemiology_MeSH S_etiology_MeSH Hot_Flashes_etiology_MeSH S_physiopathology_MeSH Hot_Flashes_physiopathology_MeSH M_Human_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_ethnology_MeSH Menopause_ethnology_MeSH S_physiology_MeSH Menopause_physiology_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Risk_Factors_MeSH M_Skin_Temperature_MeSH S_physiology_MeSH Skin_Temperature_physiology_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Sweating_MeSH S_physiology_MeSH Sweating_physiology_MeSH M_Sympatholytics_MeSH S_pharmacology_MeSH Sympatholytics_pharmacology_MeSH S_therapeutic_use_MeSH Sympatholytics_therapeutic_use_MeSH M_Time_Factors_MeSH 
****** 11473488
----K E
----T Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study.
----A An age-related decline in muscle performance is a known risk factor for falling, fracture and disability. In women, a clear deterioration is observed from early menopause. The effect of hormone replacement therapy (HRT) in preserving muscle performance is, however, unclear. This trial examined the effects of a 12-month HRT and high-impact physical exercise regimen on skeletal muscle in women in early menopause. A total of 80 women aged 50-57 years were assigned randomly to one of four groups: exercise (Ex), HRT, exercise+HRT (ExHRT) and control (Co). The exercise groups participated in a high-impact training programme. The administration of HRT (oestradiol/noretisterone acetate) or placebo was carried out double-blind. Knee extension torque and vertical jumping height were evaluated. Lean tissue cross-sectional area (LCSA) and the relative proportion of fat within the muscle compartment were measured for the quadriceps and lower leg muscles. The ExHRT group showed significant increases in knee extension torque (8.3%) and vertical jumping height (17.2%) when compared with the Co group (-7.2%). Vertical jumping height also increased after HRT alone (6.8%). The LCSA of the quadriceps was increased significantly in the HRT (6.3%) and ExHRT (7.1%) groups when compared with the Ex (2.2%) and Co (0.7%) groups. Lower leg LCSA was also increased in the ExHRT group (9.1%) when compared with the Ex (3.0%) and Co (4.1%) groups. In addition, the increase in the relative proportion of fat in the quadriceps in the Co group (16.6%) was significant compared with those in the HRT (4.9%) and ExHRT (-0.6%) groups. Thus, in post-menopausal women, muscle performance, muscle mass and muscle composition are improved by HRT. The beneficial effects of HRT combined with high-impact physical training may exceed those of HRT alone.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Analysis_of_Variance_MeSH M_Biomechanics_MeSH M_Body_Composition_MeSH M_Combined_Modality_Therapy_MeSH M_Double-Blind_Method_MeSH M_Electric_Impedance_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Muscle__Skeletal_MeSH S_drug_effects_MeSH Muscle__Skeletal_drug_effects_MeSH S_radiography_MeSH Muscle__Skeletal_radiography_MeSH M_Norethindrone_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Tomography__X-Ray_Computed_MeSH S_methods_MeSH Tomography__X-Ray_Computed_methods_MeSH M_Torque_MeSH 
****** 11486242
----K E
----T Anti-ischemic action of estrogen-progestogen continuous combined hormone replacement therapy in postmenopausal women with established angina pectoris: a randomized, placebo-controlled, double-blind, parallel-group trial.
----A The benefit of treating postmenopausal women with established cardiovascular disease with combined estrogen-progestogen hormone replacement therapy (HRT) is controversial. This study investigated the effect of treatment with estradiol and norethisterone acetate on exercise tolerance and on the frequency and severity of ischemic attacks in postmenopausal women with stable angina pectoris. A total of 74 Chinese women were recruited for this 16-week double-blind, placebo-controlled trial. They were randomly allocated into two groups; one group received placebo/placebo/placebo and the other group received placebo/estrogen-progestogen/placebo. Estrogen-progestogen continuous combined HRT increased both time to 1-mm ST depression (99.1 s, p < 0.05) compared with a mean decrease of 22.9 s with placebo (p < 0.05), and total exercise duration also showed a significant increase (32.7 s, p < 0.05) after treatment compared with placebo (2.5 s, p < 0.05). In addition, the total number of ischemic events/24 h during ambulatory electrocardiographic monitoring decreased by 0.82 events after treatment (p < 0.05) compared with an increase in the placebo group (0.94), a highly significant difference (p = 0.006). These results suggest that the administration of this particular combined hormone replacement preparation may have a beneficial effect on myocardial ischemia in postmenopausal women with established coronary disease.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Angina_Pectoris_MeSH S_drug_therapy_MeSH Angina_Pectoris_drug_therapy_MeSH S_physiopathology_MeSH Angina_Pectoris_physiopathology_MeSH M_Blood_Pressure_MeSH S_physiology_MeSH Blood_Pressure_physiology_MeSH M_China_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Electrocardiography__Ambulatory_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Exercise_Test_MeSH M_Exercise_Tolerance_MeSH M_Female_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_drug_therapy_MeSH Myocardial_Ischemia_drug_therapy_MeSH S_physiopathology_MeSH Myocardial_Ischemia_physiopathology_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11497535
----K I
----T Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial.
----A CONTEXT: Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women. OBJECTIVE: To determine whether HRT increases bone mineral density (BMD) in frail elderly women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000. PARTICIPANTS: Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. INTERVENTION: Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months. MAIN OUTCOME MEASURES: The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. RESULTS: Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%). CONCLUSIONS: In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Densitometry__X-Ray_MeSH M_Diet_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Femur_MeSH P_Frail_Elderly_MeSH M_Hip_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 11524467
----K E
----T High-dose estradiol improves cognition for women with AD: results of a randomized study.
----A OBJECTIVE: To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. METHODS: Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. RESULTS: Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. CONCLUSIONS: Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alzheimer_Disease_MeSH S_blood_MeSH Alzheimer_Disease_blood_MeSH S_drug_therapy_MeSH Alzheimer_Disease_drug_therapy_MeSH S_psychology_MeSH Alzheimer_Disease_psychology_MeSH M_Analysis_of_Variance_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH S_physiology_MeSH Cognition_physiology_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_Binding_Protein_3_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_Binding_Protein_3_metabolism_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_I_metabolism_MeSH M_Insulin-Like_Growth_Factor_II_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_II_metabolism_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH 
****** 11528357
----K E
----T Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: a direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens.
----A OBJECTIVE: To determine whether there are differences between continuous combined hormone replacement therapies on bleeding control. DESIGN: Nine hundred and forty-five postmenopausal women were randomized to one of seven double-blind treatment groups (placebo, 0.25 mg norethindrone acetate (NA)/5 microg ethinyl estradiol (EE), 1 mg NA/5 microg EE, 0.5 mg NA/10 microg EE, 1 mg NA/10 microg EE, 5 microg EE, and 10 micro EE) or unmasked 0.625 mg conjugated equine estrogens (CEE)/2.5 mg medroxyprogesterone acetate (MPA). Treatment was for 12 months; subjects kept daily diaries recording whether they had bleeding and/or spotting. RESULTS: The results focused on currently commercially available hormone replacement therapy products (femhrt [1 mg NA/5 microg EE] and Prempro [0.625 mg CEE/2.5 mg MPA]) as well as a high-dose NA/EE dose combination (1/10) over the first 6 months of use, the most critical period in establishing treatment adherence. At the end of month 6 there was a greater incidence of amenorrhea with both NA/EE dose combinations compared with CEE/MPA (p = 0.009 for 1 mg NA/5 microg EE and p = 0.006 for 1 mg NA/10 microg EE). Statistically significantly more women were amenorrheic at every month based on cumulative amenorrhea for 1 mg NA/5 microg (p < 0.05) compared with CEE/MPA; at months 3 and 6 more women were amenorrheic on 1 mg NA/10 microg EE compared with CEE/MPA using the cumulative amenorrhea parameter. CONCLUSIONS: The results indicate that statistically significantly more women attained amenorrhea based on various parameters when administered continuous combined NA/EE compared with CEE/MPA. The potential for long-term treatment compliance based on better bleeding control may optimize the opportunity to prevent osteoporosis as well as other associated health benefits.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Comparative_Study_MeSH M_Drug_Combinations_MeSH M_Estradiol_Congeners_MeSH S_pharmacology_MeSH Estradiol_Congeners_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Ethinyl_Estradiol_MeSH S_pharmacology_MeSH Ethinyl_Estradiol_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH 
****** 11530128
----K E
----T Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and serotonin 2A receptor binding.
----A OBJECTIVE: To examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide (LSD) to the platelet 5-HT(2A) receptor are influenced by postmenopausal estrogen/progestogen treatment. METHODS: Twenty-three postmenopausal women with climacteric symptoms completed this double-blind, randomized, crossover study. The women received 2 mg of estradiol continuously during four 28-day cycles. In the last 14 days of each cycle, 10 mg of medroxyprogesterone acetate, 1 mg of norethindrone acetate, or placebo was given. Before treatment, as well as once during the last week of each treatment, blood samples were collected for analysis of [3H]LSD and [3H]paroxetine binding. The power of the study setup was 81%. The study had an effect size of 0.36, corresponding to the ability to detect a 15% difference in [3H]paroxetine and [3H]LSD binding between treatments with alpha =.05 and beta =.20, based on a previously reported standard deviation within cells of 20% of the mean binding values. RESULTS: The number of platelet receptors (B(max)), or the affinity of the radioligand to the receptor (K(d)), for [3H]paroxetine binding did not change during estrogen or estrogen-progestogen treatment, nor did B(max) or K(d) for [3H]LSD binding change during the different treatments. However, in a subgroup of depressed patients, the decrease in B(max) for [3H]LSD binding during treatment was significantly more pronounced than in the nondepressed subgroup (P <.05). CONCLUSION: Estrogen treatment with or without the addition of progestogen does not affect binding to the serotonin transporter or to the serotonergic 5-HT(2A) receptor in healthy postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Blood_Platelets_MeSH S_metabolism_MeSH Blood_Platelets_metabolism_MeSH M_Carrier_Proteins_MeSH S_physiology_MeSH Carrier_Proteins_physiology_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Lysergic_Acid_Diethylamide_MeSH S_metabolism_MeSH Lysergic_Acid_Diethylamide_metabolism_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Paroxetine_MeSH S_metabolism_MeSH Paroxetine_metabolism_MeSH M_Premenstrual_Syndrome_MeSH S_blood_MeSH Premenstrual_Syndrome_blood_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Radioligand_Assay_MeSH M_Receptors__Serotonin_MeSH S_blood_MeSH Receptors__Serotonin_blood_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11549629
----K E
----T A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency.
----A The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction. Therefore, the effects of dihydrotestosterone may differ from those of T in older men. This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength, mobility, and quality of life in ambulant, community-dwelling men aged 60 yr or older. Eligible men (plasma T < or =15 nmol/liter) were randomized to undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completing the study with a high degree of compliance, dihydrotestosterone had significant effects on circulating hormones (increased dihydrotestosterone; decreased total and free testosterone, LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased total and low-density lipoprotein cholesterols; unchanged high-density lipoprotein cholesterol and triglycerides), hematopoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mass and waist to hip ratio). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, balance, or mobility tests, in cognitive function, or in quality of life scales. Dihydrotestosterone treatment had no adverse effects on prostate (unchanged prostate volumes and prostate-specific antigen) and cardiovascular (no adverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function.
----P Clinical_Trial Evaluation_Studies Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Aging_MeSH S_metabolism_MeSH Aging_metabolism_MeSH M_Androgens_MeSH S_blood_MeSH Androgens_blood_MeSH S_deficiency_MeSH Androgens_deficiency_MeSH M_Body_Height_MeSH S_drug_effects_MeSH Body_Height_drug_effects_MeSH M_Dihydrotestosterone_MeSH S_administration_&_dosage_MeSH Dihydrotestosterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Dihydrotestosterone_adverse_effects_MeSH S_pharmacology_MeSH Dihydrotestosterone_pharmacology_MeSH M_Double-Blind_Method_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH M_Gait_MeSH S_drug_effects_MeSH Gait_drug_effects_MeSH S_physiology_MeSH Gait_physiology_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Muscle__Skeletal_MeSH S_drug_effects_MeSH Muscle__Skeletal_drug_effects_MeSH S_physiology_MeSH Muscle__Skeletal_physiology_MeSH M_Neuropsychological_Tests_MeSH M_Patient_Compliance_MeSH M_Prostate_MeSH S_drug_effects_MeSH Prostate_drug_effects_MeSH S_ultrasonography_MeSH Prostate_ultrasonography_MeSH M_Quality_of_Life_MeSH S_psychology_MeSH Quality_of_Life_psychology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11549646
----K E
----T Influence of smoking on the antiosteoporotic efficacy of raloxifene.
----A The efficacy of estrogen therapy may be modified in women who smoke because of increased catabolism of estrogen and the interaction of tobacco products with the estradiol receptor. We examined whether the efficacy of raloxifene differed in smoking vs. nonsmoking women. We compared change in bone mineral density and biochemical markers of bone turnover, and incidence of new vertebral fracture in postmenopausal women of the Multiple Outcomes on Raloxifene Efficacy trial, who were randomized to either raloxifene (60 or 120 mg/d) or placebo. In the 17% of women who were current smokers, we found, compared with nonsmokers, lowered baseline trochanter bone mineral density (0.540 vs. 0.557 g/cm(2); P < 0.001) and serum osteocalcin (24.8 vs. 26.6 ng/liter; P < 0.001). Baseline urinary type I collagen breakdown products was increased among smokers (291.8 vs. 276.9 micromol/liter; P = 0.04). Body mass index was also lower in smokers (24.3 vs. 25.4; P < 0.001). After 6 months of treatment, there was no significant difference in reduction of bone turnover between smokers and nonsmokers. After 4 yr of treatment, the smoking-treatment interaction was not significant between smokers and nonsmokers for the percent increase in femoral neck bone mineral density (P = 0.25), trochanter bone mineral density (P = 0.24), and spine bone mineral density (P = 0.37). The smoking-treatment interaction for reduction in vertebral fracture risk was not significant either [odds ratio for fracture, 0.67 (0.45-0.98) for smokers and 0.56 (0.47-0.68) for nonsmokers; P = 0.44]. These results were not modified after stratification by tertiles of body mass index or when comparing heavy smokers vs. light smokers. We conclude that smoking does not influence the antiosteoporotic effect of raloxifene. This may represent an advantage over estrogen replacement therapy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Biological_Markers_MeSH M_Bone_Density_MeSH M_Bone_and_Bones_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Fractures_MeSH S_pathology_MeSH Fractures_pathology_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH S_pathology_MeSH Osteoporosis_pathology_MeSH M_Raloxifene_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Smoking_MeSH S_pathology_MeSH Smoking_pathology_MeSH 
****** 11684377
----K E
----T Chlormadinone acetate versus micronized progesterone in the sequential combined hormone replacement therapy of the menopause.
----A OBJECTIVE: The efficacy and safety of chlormadinone acetate (CA) versus micronized progesterone (P) were assessed in non-hysterectomized postmenopausal women. MATERIALS AND METHODS: This was a multicenter, randomized, parallel group study with a 6-month double-blind period followed by a 12-month open period. Patients were randomized to receive every month during 18 months percutaneous 17 beta-estradiol (E(2)) 1.5 mg/day from Day 1 to 24 of treatment cycle, combined from Day 11 to 24 to either CA 10 mg/day (n=167) or P 200 mg/day (n=169). Endometrial biopsy (EB, main analysis criterion) was performed at baseline, and at Day 18-24 of the 6th and 18th cycles. RESULTS: At Month 6, EB did not evidence any hyperplasia. EB were inadequate for assessment in 24.5% and 47.5% of patients in the CA and MP groups, respectively. CA was found to be as protective as P (96.3% and 92.0% of success). However, the hormonal status of the endometrium differed (P<0.001): a secretory endometrium was found in 81.5% of the CA patients, compared to 50.7% in the P group. These transformations resulted in predictable, cyclic bleeding in 94.5% of the CA patients, compared to only 62.3% of the P patients (P=0.0001). Unscheduled bleeding, spotting and/or metrorrhagia, were more frequent under P than under CA (17.9% and 13.7%, respectively). The beneficial effects on hot flushes were more important in the CA group than in the P (P<0.001). At Month 18, the biopsy and clinical results were similar to those obtained at Month 6. The safety profile, particularly the lipid one, was similar in both groups, except for drowsiness and dizziness, which were significantly more frequent under P than under CA. CONCLUSION: The progestative effects of CA on the endometrium and on menopause-related symptoms were at least as good as those of P. Moreover, CA resulted more often than P in secretory effects, and in satisfying bleeding patterns.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Biopsy_MeSH M_Chlormadinone_Acetate_MeSH S_administration_&_dosage_MeSH Chlormadinone_Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Chlormadinone_Acetate_adverse_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Comparative_Study_MeSH M_Dizziness_MeSH S_chemically_induced_MeSH Dizziness_chemically_induced_MeSH M_Drug_Therapy__Combination_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_adverse_effects_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH M_Sleep_Stages_MeSH M_Support__Non-U_S__Gov't_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH M_Uterine_Hemorrhage_MeSH S_epidemiology_MeSH Uterine_Hemorrhage_epidemiology_MeSH 
****** 11704101
----K E
----T Open, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 20 microg ethinyl estradiol and 150 microg desogestrel.
----A This prospective, open, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day regimen with 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) and a 21-day regimen with 20 microg EE and 150 microg desogestrel (DSG). Participants took either 23 tablets with active substances plus 5 placebo tablets (23-day EE/GSD) or 21 tablets with active substances followed by 7 days without pill-taking (21-day EE/DSG). Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 5967 treatment cycles (23-day EE/GSD: 2975 cycles; 21-day EE/DSG: 2992 cycles) were obtained from 890 participants (445 in each group).Both preparations proved to be effective contraceptives and provided good cycle control. No pregnancy during treatment was recorded. This resulted in a study Pearl Index of 0.0 for both treatments. For 23-day EE/GSD, 32.4% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 31.5% for 21-day EE/DSG. In the 23-day EE/GSD group, intracyclic bleeding episodes were reported by 48.8% of the participants in Cycle 1 but in only 15.1% in Cycle 7, and in the 21-day regimen group by 43.4% in Cycle 1 and only 14.2% in Cycle 7. Overall, intracyclic bleeding was reported in 20.9% of cycles for both treatments.A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG. In significantly (p <0.0001) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day EE/DSG group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days.Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was low (23-day EE/GSD: 6.1%; 21-day EE/DSG: 5.6%). No serious vascular adverse events were reported. More than 82% in the 23-day EE/GSD group and 79% in the 21-day EE/DSG group either lost more than 2 kg of weight or did not gain weight during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study compared to baseline.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Body_Weight_MeSH S_drug_effects_MeSH Body_Weight_drug_effects_MeSH M_Comparative_Study_MeSH M_Contraceptives__Oral__Combined_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Combined_administration_&_dosage_MeSH S_adverse_effects_MeSH Contraceptives__Oral__Combined_adverse_effects_MeSH M_Desogestrel_MeSH S_administration_&_dosage_MeSH Desogestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Desogestrel_adverse_effects_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Menstrual_Cycle_MeSH S_drug_effects_MeSH Menstrual_Cycle_drug_effects_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH S_adverse_effects_MeSH Norpregnenes_adverse_effects_MeSH M_Time_Factors_MeSH M_Treatment_Outcome_MeSH M_Uterine_Hemorrhage_MeSH 
****** 11770188
----K E
----T Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy.
----A OBJECTIVE: The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women. METHODS: Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale. RESULTS: Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse. CONCLUSIONS: The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Receptor_Modulators_MeSH S_therapeutic_use_MeSH Estrogen_Receptor_Modulators_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Liver_Function_Tests_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Sexual_Dysfunctions__Psychological_MeSH S_drug_therapy_MeSH Sexual_Dysfunctions__Psychological_drug_therapy_MeSH S_psychology_MeSH Sexual_Dysfunctions__Psychological_psychology_MeSH M_Single-Blind_Method_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 11772282
----K E
----T Trimegestone: expanding therapeutic choices for the treatment of the menopause.
----A Trimegestone is a novel norpregnane progestin, which has a potent progesterone receptor and very low androgen receptor affinities but no detectable affinity to oestrogen receptor. Trimegestone has been developed for use in conjunction with oestrogen for postmenopausal hormone replacement therapy (HRT). The dose of trimegestone required for endometrial safety was optimised in a dose ranging study. Oral trimegestone was administered at 0.05, 0.1, 0.25 and 0.5 mg/day, days 15 - 28 along with continuous oral micronised oestradiol at 2 mg daily. The majority of women in the four dose groups experienced relief of climacteric symptoms by the end of the third treatment cycle. The incidence of pre-menstrual tension-like symptoms was low and did not differ between the four dose groups. After 6 months of treatment, the bleeding pattern showed a clear dose-dependent modulation such that the higher the dose of trimegestone administered the more predictable was the day of onset of bleeding and the shorter and lighter the bleeding episodes became. This was further confirmed in another study comparing trimegestone in 0.5 and 0.25 mg doses to norethisterone acetate, where women on the 0.5 mg dose experienced more favourable bleeding pattern compared with the lower dose of 0.25 mg or to norethisterone acetate. In the dose ranging study, 96% of endometrial specimens obtained at the end of the study had secretory changes. The lipoprotein profile measured at baseline, 3 and 6 months during the dose ranging study confirmed the fact that trimegestone, irrespective of the dose, did not negate the beneficial effects of oestrogen on lipids. CONCLUSION: trimegestone is an effective and well-tolerated new progestin, which does not negate the beneficial effects of oestrogen on lipids.
----P Journal_Article Review Review__Tutorial 
----M M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_blood_MeSH Menopause_blood_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Menstrual_Cycle_MeSH S_blood_MeSH Menstrual_Cycle_blood_MeSH S_drug_effects_MeSH Menstrual_Cycle_drug_effects_MeSH M_Promegestone_MeSH S_administration_&_dosage_MeSH Promegestone_administration_&_dosage_MeSH S_adverse_effects_MeSH Promegestone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Promegestone_analogs_&_derivatives_MeSH 
****** 11779264
----K E
----T Serum estradiol level and risk of breast cancer during treatment with raloxifene.
----A CONTEXT: As endogenous estradiol increases, risk of breast cancer increases. Raloxifene competes with endogenous estrogen for binding to estrogen receptors in breast tissue. A woman's estradiol level may alter the effects of raloxifene on breast cancer and other outcomes. OBJECTIVE: To test the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels. DESIGN: Analysis of the Multiple Outcomes of Raloxifene Evaluation, a randomized, double-blind, placebo-controlled trial conducted from 1994 to 1999. SETTING: One hundred eighty community settings and medical practices in 25 countries including the United States. PARTICIPANTS: A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured by a central laboratory using a sensitive assay. Women with a history of breast cancer or estrogen use were excluded. INTERVENTION: Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years. MAIN OUTCOME MEASURE: New cases of histopathologically confirmed breast cancer in the treatment and placebo groups, stratified by estradiol levels. RESULTS: In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer (3.0% per 4 years; 95% confidence interval [CI], 1.8%-4.1%) than that of women with undetectable estradiol levels (0.6% per 4 years; 95% CI, 0%-1.1%; P =.005 for trend). Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% (95% CI, 53%-88%) lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group (absolute rate reduction, 2.2% [95% CI, 1.0%-3.5%; number needed to treat = 45]). In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with raloxifene (risk difference, -0.1%; 95% CI, -0.8% to 0.6%; P =.02 for the interaction). In this cohort, treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases. CONCLUSIONS: Measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_blood_MeSH Breast_Neoplasms_blood_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_epidemiology_MeSH Hot_Flashes_epidemiology_MeSH M_Human_MeSH M_Osteoporosis__Postmenopausal_MeSH S_blood_MeSH Osteoporosis__Postmenopausal_blood_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Raloxifene_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_MeSH M_Selective_Estrogen_Receptor_Modulators_MeSH S_therapeutic_use_MeSH Selective_Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Spinal_Fractures_MeSH S_epidemiology_MeSH Spinal_Fractures_epidemiology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Venous_Thrombosis_MeSH S_epidemiology_MeSH Venous_Thrombosis_epidemiology_MeSH 
****** 11812509
----K E
----T Lack of effects of acute estradiol on mood in postmenopausal women.
----A Chronic treatment with estrogen is believed to improve mood in postmenopausal women, and recent preclinical evidence suggests that estradiol may also affect mood and behavior through acute neuronal membrane-mediated effects on the central nervous system. This study was designed to characterize potential mood effects of single doses of transdermal estradiol in healthy postmenopausal women who were not taking hormone replacement therapy (HRT). Twelve women participated in a five-session, within-subjects, double-blind study, in which they received placebo, transdermal estradiol (0.2, 0.4, and 0.8 mg), or D-amphetamine (15 mg, oral) in a randomized order. Amphetamine was included as a positive control. Dependent measures included self-report measures of mood, physiological measures, and plasma hormone levels. Despite dose-dependent increases in plasma estradiol levels, and despite the fact that D-amphetamine produced its prototypic stimulant-like effects in these postmenopausal women, estradiol did not produce effects on mood. The finding that acute administration of exogenous estradiol did not alter mood suggests that more chronic exposure to estradiol is needed to produce mood-enhancing effects.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH S_physiology_MeSH Affect_physiology_MeSH M_Analysis_of_Variance_MeSH M_Central_Nervous_System_Stimulants_MeSH S_pharmacology_MeSH Central_Nervous_System_Stimulants_pharmacology_MeSH M_Dextroamphetamine_MeSH S_pharmacology_MeSH Dextroamphetamine_pharmacology_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 11828273
----K E
----T [Clinical effects of hormone replacement therapy with estradiol valerate and cyproterone acetate in perimenopausal women]
----A BACKGROUND: In perimenopause many women complain of psychogenic and organic disorders often connected with initial and increasing levels of hypoestrogenism. In this study we evaluated the effects of hormone replacement therapy (HRT) in symptomatic women in perimenopause. METHODS: We enrolled 100 healthy and symptomatic women who were randomly distributed to two groups for a 12-month study. Group A: 50 patients received HRT with estradiol valerate and cyproterone acetate (Pausene(R)); Group B: 50 patients were used as a control group (treated with Cacit Vitamin D30(R)). A number of clinical and instrumental tests were performed at 0, 6 and 12 months to evaluate any changes in vasomotor and urogenital symptoms, bone and serum homeostasis and possible sexual disorders. The statistical analysis was performed using the c2 test. RESULTS: The group of women receiving HRT showed a significant reduction in vasomotor clinical symptoms (p<0.001) and sexual disorders (p<0.002); this was not reflected in the control group where libido decreased steadily with apparent slight improvements only at the end of the study. The urogenital disorders disappeared almost completely in Group A, whereas they diminished in Group B. HRT patients also showed a slight increase (p<0.001) in the initial value of BMD (bone mineral density), a reduction in the marker for bone turnover and an improved lipid profile (p<0.05). These changes were unfortunately not noted in Group B. CONCLUSIONS: On the basis of these results we conclude that HRT appeared to have a beneficial effect on perimenopausal clinical symptoms over the 12-month period, leading to marked improvements in the psychophysical wellbeing of symptomatic women in perimenopause.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Climacteric_MeSH M_Cyproterone_Acetate_MeSH S_therapeutic_use_MeSH Cyproterone_Acetate_therapeutic_use_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH 
****** 11829697
----K I
----T Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial.
----A CONTEXT: Postmenopausal hormone therapy is commonly used by women for disease prevention, but its effects on quality of life have not been well documented. OBJECTIVE: To determine the effect on quality of life of estrogen plus progestin therapy used as secondary prevention in women with coronary artery disease. DESIGN, SETTING, AND PARTICIPANTS: A total of 2763 postmenopausal women with documented coronary artery disease (mean age, 67 years) in the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled, double-blind trial conducted from January 1993 to July 1998 at outpatient and community settings at 20 US clinical centers. INTERVENTION: Participants were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) for 36 months. MAIN OUTCOME MEASURES: Physical activity, measured by the Duke Activity Status Index; energy/fatigue and mental health, measured by RAND scales; and depressive symptoms, measured on the Burnam screening scale, at 3 years of follow-up. RESULTS: In all patients, scores declined significantly over 3 years for physical function (-3.8; P<.001), mental health (-0.6; P =.05), and energy/fatigue (-3.8; P<.001), but depressive symptoms were not significantly changed (P =.20). The effect of hormone therapy on these measures depended on the presence (n = 434) or absence (n = 2325) of flushing at study entry. Women with flushing who were assigned to hormone therapy had improved mental health (+2.6 vs - 0.5; P =.04) and fewer depressive symptoms (-0.5 vs + 0.007; P =.01) over follow-up compared with those assigned to placebo. Women without flushing who were assigned to hormone therapy had greater declines in physical function (-4.2 vs -3.3; P =.04) and energy/fatigue (-4.6 vs -3.1; P =.03) over follow-up. Quality-of-life scores were significantly lower among patients with older age, diabetes, hypertension, chest pain, or heart failure. These differences in quality of life among women classified by clinical characteristics were much greater than the effects of hormone therapy. CONCLUSION: Hormone therapy has mixed effects on quality of life among older women. The effects of hormone therapy depend on the presence of menopausal symptoms; women without flushing had greater declines in physical measures, while women with flushing had improvements in emotional measures of quality of life.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Coronary_Arteriosclerosis_MeSH S_prevention_&_control_MeSH Coronary_Arteriosclerosis_prevention_&_control_MeSH M_Depression_MeSH S_epidemiology_MeSH Depression_epidemiology_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH P_Exertion_MeSH M_Fatigue_MeSH S_epidemiology_MeSH Fatigue_epidemiology_MeSH M_Female_MeSH M_Hot_Flashes_MeSH M_Human_MeSH M_Linear_Models_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Mental_Health_MeSH M_Multivariate_Analysis_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH P_Quality-Adjusted_Life_Years_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH 
****** 11835027
----K E
----T Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease.
----A BACKGROUND: Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men. METHODS: We used 99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 +/- 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline. RESULTS: Serum testosterone increased 137 +/- 58% and 488 +/- 113%, and estradiol levels increased 27 +/- 46% and 76 +/- 57%, (P <.001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression. CONCLUSIONS: Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_blood_MeSH Myocardial_Ischemia_blood_MeSH S_drug_therapy_MeSH Myocardial_Ischemia_drug_therapy_MeSH S_radionuclide_imaging_MeSH Myocardial_Ischemia_radionuclide_imaging_MeSH M_Radiopharmaceuticals_MeSH S_diagnostic_use_MeSH Radiopharmaceuticals_diagnostic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Technetium_Tc_99m_Sestamibi_MeSH S_diagnostic_use_MeSH Technetium_Tc_99m_Sestamibi_diagnostic_use_MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_pharmacology_MeSH Testosterone_pharmacology_MeSH M_Tomography__Emission-Computed__Single-Photon_MeSH 
****** 11836043
----K E
----T The efficacy of two dosages of a continuous combined hormone replacement regimen.
----A OBJECTIVES: To evaluate the efficacy of a low-dose combination of estradiol (E2) and norethisterone acetate (NETA) on bone markers, lipid and bleeding profiles and menopausal symptoms. METHOD: Ninety-six healthy Chinese postmenopausal women were allocated randomly to receive 1 mg E2/0.5 mg NETA (low-dose hormone replacement therapy (HRT)) or 2 mg E2/1 mg NETA (high-dose HRT) for 6 months. RESULTS: Bone resorption markers (collagen I N-terminal telopeptides (NTX) and deoxypyridinoline (dPyr)) were significantly reduced; -66 and -32%, respectively, in high-dose HRT versus -55 and -24%, respectively, in low-dose HRT. Bone-specific alkaline phosphatase remained unchanged with either combination of hormones. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were decreased significantly (-12 and -13%, respectively, in high-dose HRT vs. -7 and -8% in low-dose HRT). High density lipoprotein cholesterol (HDL-C) was decreased to a lesser extent in low-dose HRT and triglycerides (TG) levels remained unchanged. Both the low and high-dose HRT were effective in alleviating menopausal symptoms. After 6 months of treatment, 2% of women in the low-dose HRT were bleeding compared with 23% in the high-dose HRT. Breast pain occurred in 2% of women in low-dose HRT compared with 15% in high-dose HRT. The endometrium in the majority of the women remained normal. CONCLUSION: Menopausal symptoms were reduced effectively in postmenopausal women on either low-dose or high-dose HRT. TC, LDL-C levels and bone resorption markers were reduced in a dose-dependent manner. Low-dose HRT provided a better bleeding profile and the incidence of breast pain was low.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Amino_Acids_MeSH S_blood_MeSH Amino_Acids_blood_MeSH M_Asian_Continental_Ancestry_Group_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Collagen_MeSH S_blood_MeSH Collagen_blood_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_genetics_MeSH Hot_Flashes_genetics_MeSH M_Human_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_genetics_MeSH Osteoporosis__Postmenopausal_genetics_MeSH M_Peptides_MeSH S_blood_MeSH Peptides_blood_MeSH M_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Singapore_MeSH M_Treatment_Outcome_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH M_Uterine_Hemorrhage_MeSH 
****** 11886769
----K I
----T Efficacy of a new 7-day transdermal sequential estradiol/levonorgestrel patch in women.
----A OBJECTIVE: To investigate the efficacy and tolerability of a new 7-day transdermal sequential estradiol/levonorgestrel patch (Fem7 Combi; Merck KGaA; Germany), versus placebo, as hormone replacement therapy in menopausal women. METHODS: A multicentre, randomized, clinical study consisting of a 3-week screening phase, a 12-week double-blind, placebo-controlled treatment phase, and a 12-week open, follow-up phase. Women aged 40-65 years with an intact uterus and menopausal complaints were randomized to either 2 weeks of an estradiol mono patch (50 microg per 24 h) followed by 2 weeks of an estradiol/levonorgestrel combination patch (50 microg/10 microg per 24 h), or a placebo patch, for three 28-day cycles. Changes in the Kupperman Index and the frequency of hot flushes were assessed. RESULTS: The sequential use of a 7-day estradiol patch and a 7-day estradiol/levonorgestrel patch was superior to placebo in reducing menopausal symptoms, and was well tolerated. At the end of the treatment phase, there was a statistically significant reduction in the Kupperman Index score versus placebo (P<0.0001), and a statistically significant difference between groups in the proportion of patients with a reduction in the number of hot flushes (at least 50% versus baseline). During the open follow-up phase, there was a marked reduction in the Kupperman Index score and the number of hot flushes for patients switched from placebo to active study medication. The active medication was effective throughout the 1-week application period. CONCLUSIONS: The new 7-day transdermal sequential estradiol/levonorgestrel patch was well tolerated, providing rapid and effective relief of menopausal symptoms. The addition of low-dose levonorgestrel did not influence the beneficial effects of estradiol.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Germany_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH S_therapeutic_use_MeSH Levonorgestrel_therapeutic_use_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Treatment_Outcome_MeSH 
****** 11895463
----K E
----T Oestrogen attenuates coronary vasoconstriction after angioplasty: role of endothelin-1.
----A BACKGROUND AND AIMS: There were controversies as to whether endothelin-1 is released after coronary angioplasty. We sought to determine whether endothelin-1 is released after coronary angioplasty and whether oestrogen administration can affect coronary vasomotor tone by reducing endothelin-1 concentrations. METHODS: The study was designed to prospectively investigate 24 consecutive patients scheduled for elective coronary angioplasty. Patients were randomized into two groups according to whether they did not (group 1, n = 12) or did (group 2, n = 12) have intracoronary treatment with oestrogen. Quantitative coronary angiography was monitored at baseline, immediately after successful angioplasty, and 15 min after the last deflation. Blood samples for measuring the levels of endothelin-1 were drawn from the ascending aorta and the coronary sinus simultaneously before angioplasty and 15 min after balloon dilatation. RESULTS: The diameters of the coronary artery at the dilated segments were significantly reduced 15 min after dilation compared with those immediately after dilation in group 1 from 3.20 +/- 0.22 to 2.30 +/- 0.23 mm (P < 0.001), respectively. The vasoconstriction was significantly blunted in group 2. The endothelin-1 levels from the coronary sinus rose significantly, by 29%, 15 min after angioplasty in group 1, which was attenuated after administering oestrogen. Significant correlation was found between the changes of coronary vasomotion of the dilated segment and endothelin-1 levels (r = 0.70, P = 0.01). CONCLUSION: Endothelin-1 is released into the coronary circulation after angioplasty, and this vasoactive substance may contribute to the occurrence of vasoconstriction. The vasoconstriction is attenuated by oestrogen by reducing the endothelin-1 levels. This finding provided a new strategy to treat coronary vasoconstriction after angioplasty.
----P Clinical_Trial Journal_Article 
----M P_Angioplasty__Transluminal__Percutaneous_Coronary_MeSH M_Aorta_MeSH S_metabolism_MeSH Aorta_metabolism_MeSH M_Blood_Pressure_MeSH M_Coronary_Arteriosclerosis_MeSH S_blood_MeSH Coronary_Arteriosclerosis_blood_MeSH S_diagnosis_MeSH Coronary_Arteriosclerosis_diagnosis_MeSH S_therapy_MeSH Coronary_Arteriosclerosis_therapy_MeSH M_Coronary_Vessels_MeSH S_metabolism_MeSH Coronary_Vessels_metabolism_MeSH M_Electrocardiography_MeSH M_Endothelin-1_MeSH S_blood_MeSH Endothelin-1_blood_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Lactates_MeSH S_blood_MeSH Lactates_blood_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_blood_MeSH Myocardial_Ischemia_blood_MeSH S_diagnosis_MeSH Myocardial_Ischemia_diagnosis_MeSH S_therapy_MeSH Myocardial_Ischemia_therapy_MeSH M_Prospective_Studies_MeSH M_Sinus_of_Valsalva_MeSH S_metabolism_MeSH Sinus_of_Valsalva_metabolism_MeSH M_Vasoconstriction_MeSH S_drug_effects_MeSH Vasoconstriction_drug_effects_MeSH S_physiology_MeSH Vasoconstriction_physiology_MeSH 
****** 11896091
----K E
----T Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial.
----A PURPOSE: Vasomotor symptoms, such as hot flashes and night sweats, in breast cancer survivors are often worsened by chemotherapy and tamoxifen, and/or the discontinuation of hormone replacement therapy at diagnosis. This study evaluated the acceptability and effectiveness of a soy beverage containing phytoestrogens as a treatment for hot flashes in postmenopausal women with breast cancer. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted in postmenopausal women with moderate hot flashes who were previously treated for early-stage breast cancer. Women were stratified for tamoxifen use and randomized to a soy beverage (n = 59) containing 90 mg of isoflavones or to a placebo rice beverage (n = 64). Women recorded the number and severity of hot flashes daily with a daily menopause diary for 4 weeks at baseline and for 12 weeks while consuming 500 mL of a soy or placebo beverage. RESULTS: There were no significant differences between the soy and placebo groups in the number of hot flashes or hot flash scores. However, presumably because of a strong placebo effect, both groups had significant reductions in hot flashes. Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy. The mean serum genistein concentration at 6 weeks was significantly higher in women who consumed soy (0.61 +/- 0.43 micromol/L) compared with placebo (0.43 +/- 0.37 micromol/L) (P =.02). Overall acceptability and compliance were high and similar in both groups. CONCLUSION: The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo. Future research into other compounds is recommended to identify safe and effective therapies for hot flashes in breast cancer survivors.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Breast_Neoplasms_MeSH S_complications_MeSH Breast_Neoplasms_complications_MeSH M_Double-Blind_Method_MeSH M_Estrogens__Non-Steroidal_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_etiology_MeSH Hot_Flashes_etiology_MeSH M_Human_MeSH P_Isoflavones_MeSH M_Middle_Aged_MeSH M_Plant_Preparations_MeSH M_Postmenopause_MeSH M_Soybeans_MeSH S_chemistry_MeSH Soybeans_chemistry_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 11908491
----K E
----T A randomized trial of sodium fluoride (60 mg) +/- estrogen in postmenopausal osteoporotic vertebral fractures: increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures.
----A Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean +/- SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 31). In the second study 34 patients, age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17; E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to +/- NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p=0.004); total hip -4.1% (p = 0.003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p < 0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Anthropometry_MeSH M_Body_Height_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Calcium_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Therapy__Combination_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Fractures__Stress_MeSH S_chemically_induced_MeSH Fractures__Stress_chemically_induced_MeSH S_prevention_&_control_MeSH Fractures__Stress_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_chemically_induced_MeSH Osteoporosis__Postmenopausal_chemically_induced_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Sodium_Fluoride_MeSH S_adverse_effects_MeSH Sodium_Fluoride_adverse_effects_MeSH S_therapeutic_use_MeSH Sodium_Fluoride_therapeutic_use_MeSH M_Spinal_Fractures_MeSH S_chemically_induced_MeSH Spinal_Fractures_chemically_induced_MeSH S_prevention_&_control_MeSH Spinal_Fractures_prevention_&_control_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11908492
----K I
----T Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial.
----A This 2-year, double-masked, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy in preventing bone loss in postmenopausal women of two doses of transdermal 17betaestradiol (estradiol) delivered by a matrix patch, compared with placebo. One hundred and sixty healthy, hysterectomized postmenopausal volunteers aged 40-60 years with serum estradiol levels < 20 pg/ml were started on treatment at four centers in The Netherlands. Every 6 months, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, non-dominant wrist and left hip, and markers of bone turnover were assessed in urine and serum. The treatment arms were: estradiol, 100 microg/day (E-100, n = 53), oestradiol, 50 microg/day (E-50, n = 54), placebo (P-100, placebo to E-100, n = 27 or P-50, placebo to E-50, n = 26). Treatment was continued for up to 2 years. After 24 months, BMD of the lumbar spine in the E-100 group differed by 7.7% [5.8-9.5%] (mean [95% confidence interval]) from the placebo group and showed a mean (s.e.m.) increase in BMD from baseline of 5.9% (0.69%). For the E-50 group the difference compared with placebo was 6.2% [4.4-8.0%] and the absolute increase was 4.5% (0.62%); in the placebo group, the absolute change was -2.3% (0.48%). In the total wrist, the changes were: E-100: difference compared with placebo 2.5% [1.5 3.6%], absolute increase 0.6% (0.3%); E-50: difference compared with placebo 2.9% [1.8-3.9%], absolute increase 0.7% (0.25%); and absolute change on placebo: -2.5% (0.35%). In the total hip, the changes were: E-100: difference compared with placebo 3.7% [2.2-5.2%], absolute increase 2.8% (0.5%); E-50: difference compared with placebo: 3.2% [1,8-4.7%], absolute change 2.4% (0.36%); and absolute change on placebo -1.4% (0.66%). Three markers of bone turnover--serum bone-specific alkaline phosphatase, serum osteocalcin and urinary CTX--fell significantly during the trial. Breast pain was reported by 8% of women on placebo, by 6% of women on E-50 and by 17% of women on E-100. Estradiol delivered by the E-50 matrix patch effectively reversed bone loss in hysterectomized postmenopausal women with few side-effects. The marginal additional gain in BMD with the higher dose may be offset by a more important side effect profile.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hip_Joint_MeSH S_physiopathology_MeSH Hip_Joint_physiopathology_MeSH M_Human_MeSH M_Hysterectomy_MeSH S_adverse_effects_MeSH Hysterectomy_adverse_effects_MeSH M_Lumbar_Vertebrae_MeSH S_physiopathology_MeSH Lumbar_Vertebrae_physiopathology_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_etiology_MeSH Osteoporosis__Postmenopausal_etiology_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Wrist_Joint_MeSH S_physiopathology_MeSH Wrist_Joint_physiopathology_MeSH 
****** 11907928
----K I
----T Hormonal treatment and psychological function during the menopausal transition: an evaluation of the effects of conjugated estrogens/cyclic medroxyprogesterone acetate.
----A OBJECTIVE: To investigate the effect of hormone treatment on psychosocial distress of women during the menopausal transition (aged 40-52 years, still menstruating and with minor symptoms), in a study carefully designed to reduce bias and placebo effect. METHODS: The study was randomized, controlled by placebo, blinded to the subject, investigators and biostatistician, crossed-over after 6 months, and evaluated by a 77-item questionnaire every month for 12 months. The medication tested was continuous conjugated estrogens (Premarin) and cyclic medroxyprogesterone acetate (Provera). RESULTS: Of an eligible 105 apparently healthy women, recruited by advertisement, 83 completed the questionnaires for the study. Randomization was successful. While there was a substantial variation over time in the change of scores for all the psychosocial outcomes, there was no significant difference between active and placebo treatment when order of treatment allocation was ignored. However, a strong and consistent effect of the order of treatment allocation for many of the scores was found; in particular, the effect of active treatment was substantially stronger when it was administered second. Positive effects of active treatment were found for the score for the overall symptom rating test (p < 0.009) and its components of depression and feeling of inadequacy (p = 0.011; p = 0.001, respectively). CONCLUSIONS: The use of hormones, given as a continuous estrogen and cyclic progestogen formulation after a formal calibration/run-in period, may have a beneficial effect on psychosocial distress experienced by women towards the end of their reproductive function.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Anxiety_MeSH S_drug_therapy_MeSH Anxiety_drug_therapy_MeSH M_Depression_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Menopause_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Patient_Dropouts_MeSH M_Placebos_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11907946
----K I
----T Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms?
----A OBJECTIVES: This study compared two continuous-combined hormone replacement therapy (HRT) formulations, 1 mg estradiol (E2)/0.25 mg norethisterone acetate (NETA) and 1 mg E2/0.5 mg NETA, with placebo, with regard to the efficacy for vasomotor symptom relief in menopausal women. METHODS: A total of 119 women aged 45-61 years with moderate and severe hot flushes and with amenorrhea for at least 3 months were randomly assigned to 12 weeks' treatment with 1 mg E2/0.25 mg NETA, 1 mg E2/0.5 mg NETA or placebo. The number and severity of hot flushes, as well as any vaginal bleeding, were recorded on a daily basis. The Kupperman Menopausal Index, Greene Climacteric Scale and visual analog scales for various symptoms were assessed before and after treatment. Subpopulation analysis according to menopausal status was performed. RESULTS: Both combinations significantly reduced the number and severity of hot flushes, compared to placebo. A reduction of approximately 85% in vasomotor symptomatology occurred in the two combination groups by week 4 of treatment, and this was further diminished throughout the study to approximately 97% reduction by week 12. At the end of the study, 85% of the women receiving 1 mg E2/0.5 mg NETA and 71% of the women receiving 1 mg E2/0.25 mg NETA were considered to the clinically adequate responders to treatment. Both combinations were associated with significant improvements, compared to placebo, in visual analog scales for overall general condition, Kupperman Menopausal Index, and Greene Climacteric vasomotor and psychological subscales. While both combinations resulted in similar bleeding profiles in postmenopausal women, the combination of 1 mg E2/0.5 mg NETA resulted in the lowest incidence of bleeding in late perimenopausal women. CONCLUSIONS: The combinations of 1 mg E2/0.25 mg NETA and 1 mg E2/0.5 mg NETA rapidly relieve vasomotor symptoms and are efficacious in the majority of menopausal women, including those with severe hot flushes.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH 
****** 11910586
----K E
----T Effect of an estradiol gel with monthly or quarterly progestogen on menopausal symptoms and bleeding.
----A OBJECTIVE: To assess the acceptability, efficacy and endometrial safety of transdermal estradiol gel (Divigel/Sandrena) combined with monthly or quarterly oral progestogen (medroxyprogesterone acetate). METHODS: This 12-month, multicenter, open-label study was carried out at 12 study centers in Finland and Sweden. A total of 395 postmenopausal women received 1 mg estradiol in 1 g gel, daily, with oral medroxyprogesterone acetate 10 mg for the first 12 days every month (groups I and III) or every 3 months (group II). The main outcome measures were relief of climacteric symptoms, bleeding patterns and endometrial safety. RESULTS: All regimens reduced the severity of hot flushes, sweating episodes and vaginal dryness. In groups I and III, approximately 80% and 70% of women, respectively, had regular monthly withdrawal bleeding (excepting the first cycle), with irregular bleeding in 8.3% and 5.3% of treatment months. In group II, approximately 94% of women had regular tri-monthly withdrawal bleeding, with irregular bleeding in 10.7% of the treatment months. Endometrial hyperplasia was observed in 0.3% of women. More than 87% of subjects completed the study, and 97% of these rated the gel as acceptable or convenient. CONCLUSIONS: Both the 1- and 3-month regimens were equally effective in controlling climacteric symptoms and protecting against endometrial hyperstimulation. The bleeding patterns were comparable between groups and were similar to those reported for oral estrogens. Estradiol gel was highly acceptable to the majority of women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Comparative_Study_MeSH M_Drug_Administration_Schedule_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Finland_MeSH M_Gels_MeSH M_Hot_Flashes_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Sweden_MeSH M_Treatment_Outcome_MeSH M_Uterine_Hemorrhage_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH M_Women's_Health_MeSH 
****** 11910619
----K I
----T Low-dose esterified estrogens (0.3 mg/day): long-term and short-term effects on menopausal symptoms and quality of life in postmenopausal women.
----A OBJECTIVE: To study the impact of low-dose unopposed esterified estrogens on menopausal symptoms and quality of life. METHODS: In a long-term, 2-year, randomized, double-blind, placebo-controlled study, 204 postmenopausal women were treated with esterified estrogens 0.3 mg daily or placebo. Menopausal symptoms were assessed with a modified Kupperman index at baseline, 3, 6 and thereafter every 6 months. In a second 12-week, open-label, short-term pilot study, 25 postmenopausal women with moderate to severe vasomotor symptoms were treated with esterified estrogens 0.3 mg daily for 12 weeks. Vasomotor symptoms and quality of life were assessed using the Greene scale and Quality of Life Menopause Scale (QUALMS). RESULTS: In the long-term study, significant (p < 0.05) reductions in total symptom scores were observed at each time point with esterified estrogens compared with placebo. Somatic symptom scores (hot flushes, night sweats, vaginal dryness) decreased significantly (p < 0.01) in patients treated with esterified estrogens 0.3 mg compared to baseline and placebo. In the short-term, open-label pilot study, the incidence of vasomotor symptoms was significantly (p < 0.01) reduced with esterified estrogens 0.3 mg from week 4 until the study end. Significant (p < 0.05) improvements versus baseline were seen in the somatic and vasomotor/sleep domains and in the total quality-of-life score. CONCLUSIONS: Esterified estrogens 0.3 mg given daily provide adequate menopausal symptom relief and improved quality of life in postmenopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH M_Endometrial_Hyperplasia_MeSH S_epidemiology_MeSH Endometrial_Hyperplasia_epidemiology_MeSH M_Equilin_MeSH S_administration_&_dosage_MeSH Equilin_administration_&_dosage_MeSH S_adverse_effects_MeSH Equilin_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Equilin_analogs_&_derivatives_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrone_MeSH S_administration_&_dosage_MeSH Estrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrone_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH P_Postmenopause_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH M_Sweating_MeSH M_Uterine_Hemorrhage_MeSH S_epidemiology_MeSH Uterine_Hemorrhage_epidemiology_MeSH M_Vaginal_Diseases_MeSH S_drug_therapy_MeSH Vaginal_Diseases_drug_therapy_MeSH 
****** 11910651
----K E
----T Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women.
----A OBJECTIVE: To compare the efficacy and endometrial safety of two estradiol valerate/dienogest combinations with Kliogest in the treatment of postmenopausal symptoms. DESIGN: This was a double-blind, randomized, multicenter study. METHODS: Patients were randomized to estradiol valerate 2.0 mg/dienogest 2.0 mg (Climodien), estradiol valerate 2.0 mg/dienogest 3.0 mg (E2Val 2/DNG 3); or estradiol 2.0 mg/estriol 1.0 mg/norethisterone acetate 1.0 mg (Kliogest) once daily for 1 year. The primary efficacy variable was the Kupperman index. Endometrial safety was determined primarily by biopsy. RESULTS AND CONCLUSIONS: Climodien and E2Val 2/DNG 3 were therapeutically equivalent to Kliogest (mean changes in Kupperman index -20.1, -19.0 and -18.3, respectively). No statistically significant differences existed between treatment groups in the severity of postmenopausal symptoms. The incidences of endometrial atrophy were similar in all groups. Climodien appeared to be superior to Kliogest in terms of vaginal bleeding pattern, whereas E2Val 2/DNG 3 was associated with a slightly higher incidence and greater intensity of vaginal bleeding. The incidences of adverse events were similar in all groups. A greater proportion of women in the Kliogest and E2Val 2/DNG 3 groups experienced vaginal bleeding, whereas breast problems were more common with Climodien. Climodien and E2Val 2/DNG 3 induced desirable changes in insulin-like growth factor I (decrease) and sex hormone binding globulin (increase) that were not seen with Kliogest.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Biopsy_MeSH M_Breast_Diseases_MeSH S_chemically_induced_MeSH Breast_Diseases_chemically_induced_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Endometrial_Hyperplasia_MeSH S_chemically_induced_MeSH Endometrial_Hyperplasia_chemically_induced_MeSH S_pathology_MeSH Endometrial_Hyperplasia_pathology_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH M_Estriol_MeSH S_administration_&_dosage_MeSH Estriol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estriol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Nandrolone_MeSH S_administration_&_dosage_MeSH Nandrolone_administration_&_dosage_MeSH S_adverse_effects_MeSH Nandrolone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Nandrolone_analogs_&_derivatives_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Therapeutic_Equivalency_MeSH M_Treatment_Outcome_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH 
****** 11915854
----K I
----T Comparison of Alora estradiol matrix transdermal delivery system with oral conjugated equine estrogen therapy in relieving menopausal symptoms. Alora Study Group.
----A OBJECTIVE: To compare the efficacy of two strengths of an estradiol matrix transdermal delivery system with daily oral doses of conjugated equine estrogens in reducing the frequency of moderate-to-severe hot flushes in postmenopausal women. DESIGN: The design of the study provided for the following treatment regimens: an estradiol transdermal delivery system (Alora 0.05 or 0.1 mg/day) administered twice weekly or oral doses of conjugated equine estrogens (CEE 0.625 or 1.25 mg) administered daily were given to 321 highly symptomatic postmenopausal women for 12 weeks following a randomized, parallel-group, double-blind, double-dummy design. RESULTS: Results indicate no statistically significant differences at any time point in mean frequency or mean percentage reduction in frequency of moderate-to-severe hot flushes between patients given Alora 0.1 mg/day and those receiving CEE 1.25 mg/day. Similarly, no significant differences were observed at any time in mean frequency of moderate-to-severe hot flushes between the Alora 0.05 mg/day and CEE 0.625 mg/day groups, although the group receiving CEE 0.625 mg/day exhibited a statistically greater percentage reduction than the Alora 0.05 mg/day group at weeks 3, 4 and 8. By week 12, these two treatments were statistically indistinguishable. There were no serious or unexpected adverse events with the two transdermal systems and local skin tolerability was excellent. Other estrogenic effects such as restoration of vaginal cytology, breast tenderness and unexpected vaginal bleeding were comparable between transdermal and oral administration groups except for a lower incidence of bleeding in those women receiving the lower dose transdermal regimen.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11911720
----K I
----T Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study.
----A BACKGROUND: Accelerated bone loss after stopping hormone therapy (HRT) is postulated to explain the lack of hip-fracture protection conferred by former HRT use. The abbreviation HRT (traditionally standing for "hormone replacement therapy") is used herein because of its wide recognition in the field. However, the pharmacological doses of estrogens and progestins used are not truly "replacement" in nature. OBJECTIVES: To determine whether women lose bone mineral density (BMD) after stopping HRT; to assess whether their rate of loss is significantly greater than that of women not undergoing HRT; and to determine whether long-term HRT is associated with continued gains in BMD. METHODS: A total of 495 women who were adherent to assigned treatment in the 3-year Postmenopausal Estrogen/Progestin Interventions randomized controlled trial (PEPI-RCT) and who had an additional BMD measurement during the PEPI Safety Follow-up Study were observed for an average of 3 years during and 4 years after the PEPI-RCT. RESULTS: Women who stopped HRT after 1 year during the PEPI-RCT had annual rates of BMD change of -0.54% (hip) and -0.81% (spine) during the following 2 years. Those who underwent HRT for 3 years during the PEPI-RCT and then discontinued it had annual changes of -1.01% (hip) and -1.04% (spine). Rates of BMD loss among women who stopped HRT during or after the PEPI-RCT did not differ significantly from those of women who did not undergo HRT, who lost bone at a rate of approximately 1% yearly during the first year of the PEPI-RCT and about half that rate afterward. Women who continued HRT after the PEPI-RCT did not show additional BMD gains. CONCLUSIONS: Our results do not support the hypothesis that bone is lost at an unusually fast rate after discontinuation of HRT, nor do they suggest that longer-term HRT leads to additional BMD gain beyond that evident after 3 years.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_Congeners_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Time_Factors_MeSH P_Withholding_Treatment_MeSH 
****** 11915576
----K E
----T The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy.
----A The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate (MPA) during postmenopausal hormone replacement therapy (HRT) in women with and without a history of premenstrual syndrome (PMS). The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden. The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle. The main outcome measures were mood and physical symptoms noted on a daily rating scale. We found that physical symptoms did not differ between 10 and 20 mg MPA. Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA. In women with previous PMS the higher dose of MPA enhanced positive mood symptoms. With respect to mood and physical symptoms, the aim to lower MPA doses in HRT is unwarranted.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M P_Affect_MeSH M_Blood_Pressure_MeSH M_Body_Weight_MeSH M_Cross-Over_Studies_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH M_Middle_Aged_MeSH M_Periodicity_MeSH P_Postmenopause_MeSH M_Premenstrual_Syndrome_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11922259
----K E
----T Relationships between clinical attachment level and spine and hip bone mineral density: data from healthy postmenopausal women.
----A BACKGROUND: There are physiological reasons to expect an association between bone mineral density of the spine and hip and attachment loss. To this point, however, most studies have found no correlation. METHODS: The 135 patients in this report were part of a randomized controlled trial of estrogen replacement. All patients were in good oral health at entry and received annual oral prophylaxis as part of the study. Standard probing measurements were made with a pressure sensitive probe at 6 sites on each tooth. Bone mineral density was measured with dual-energy x-ray absorbtiometry at the lumbar spine (anterior-posterior and lateral) and proximal femur (neck, trochanter, intertrochanter, Ward's triangle, and total area). These procedures were performed at baseline and at annual intervals for 3 years. RESULTS: Correlations between cross-sectional measurements of clinical attachment level and bone mineral density were very weak, and did not approach statistical significance (-0.06 < or =r < or =0.10, 0.15 < or =P < or =0.75). A few somewhat stronger correlations were found between longitudinal changes in bone mineral density and attachment (-0.20 < or = r < or =-0.02, 0.02 < or = P < or =0.81). Although the correlations in the longitudinal changes were weak, they were consistently in the direction of greater bone mineral density being associated with less attachment loss. CONCLUSIONS: There is no clear association between clinical attachment level and bone mineral density of the lumbar spine and proximal femur, whether examined on a cross-sectional or longitudinal basis. Patterns in the data suggest there may be a weak association in the longitudinal changes.
----P Clinical_Trial Comment Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH P_Bone_Density_MeSH M_Cross-Sectional_Studies_MeSH M_Densitometry__X-Ray_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Femur_MeSH S_pathology_MeSH Femur_pathology_MeSH M_Gingival_Recession_MeSH S_physiopathology_MeSH Gingival_Recession_physiopathology_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Lumbar_Vertebrae_MeSH S_pathology_MeSH Lumbar_Vertebrae_pathology_MeSH M_Middle_Aged_MeSH M_Periodontal_Attachment_Loss_MeSH S_physiopathology_MeSH Periodontal_Attachment_Loss_physiopathology_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Regression_Analysis_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 11932272
----K E
----T Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis.
----A This prospective randomized, double-blind, placebo-controlled, clinical trial was performed to evaluate the effectiveness of estrogens plus low-dose alendronate on bone metabolism. A total of 150 surgically postmenopausal women with osteoporosis were randomized in three groups: group A, micronized E2 (2 mg/d) plus standard-dose alendronate (10 mg/d); group B, micronized E2 plus low-dose alendronate (5 mg/d); and group C, micronized E2 plus placebo (one tablet per day). In all women, bone mineral density (BMD) and serum bone metabolism markers were assessed at admission and every 6 months for 2 yr. After 2 yr, BMD significantly increased compared with baseline in all groups. The percentage BMD change was significantly higher in groups A and B than in group C. The differences in BMD detected between groups A and B were not statistically significant. Since the 6-month follow-up and throughout the study, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were significantly reduced in all groups. Serum bone alkaline phosphatase levels significantly decreased in groups A and B, without difference between them, in comparison with group C. In conclusion, in surgically postmenopausal osteoporotic women treated with estrogen replacement, the addition of alendronate at a low dose of 5 mg daily induces a gain of bone mass not significantly different in comparison with that obtained using a standard dose of 10 mg daily.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Alendronate_MeSH S_administration_&_dosage_MeSH Alendronate_administration_&_dosage_MeSH S_adverse_effects_MeSH Alendronate_adverse_effects_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Biological_Markers_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_and_Bones_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH P_Hysterectomy_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_metabolism_MeSH Osteoporosis__Postmenopausal_metabolism_MeSH M_Prospective_Studies_MeSH 
****** 11932273
----K E
----T Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women.
----A Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion. Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms. However, estrogen-androgen (E/A) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass. The objective of this 16-wk, double-blind, randomized, parallel group clinical trial was to compare esterified estrogen plus methyltestosterone (1.25 mg estrogen + 2.5 mg methyltestosterone/d; E/A group) vs. esterified estrogen alone (1.25 mg/d; E group) on body composition. Forty postmenopausal women (mean age, 57 yr) participated. Compared with estrogen treatment alone, women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts (P < 0.05). After E/A treatment, there were statistically significant increases in lean body mass by 1.232 kg [0.181 +/- 0.004, 0.81 +/- 0.057, and 0.24 +/- 0.009 kg in the upper body (P = 0.021), trunk (P = 0.001), and lower body (P = 0.047), respectively]. In the E group, the increase was 0.31 +/- 0.004, 0.021 +/- 0.03, and 0.056 +/- 0.05 kg in the upper body, trunk, and lower body, respectively. In the E/A group, body fat was reduced by 0.90 kg (P = 0.18 for the trunk only), and percentage body fat declined by 7.4% (P < or = 0.05 for all body parts). Lower body strength increased by 23.1 kg (51 lb) in the E/A group vs. only 11 kg (24.25 lb) in the E group (P = 0.002 between groups). A statistically significant increase in weight (2.7 +/- 5.1 vs. 0.1 +/- 4.6 lb; P < 0.05) was observed in the E/A group compared with the E group. When subjects were given self-reporting questionnaires, more improvement was noted in sexual functioning and quality of life in the E/A group when compared with patients receiving E alone. There were no noteworthy side effects. In conclusion, E/A replacement therapy can improve body composition, lower-body muscle strength, quality of life, and sexual functioning in postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Aged_MeSH M_Anthropometry_MeSH M_Body_Composition_MeSH S_drug_effects_MeSH Body_Composition_drug_effects_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Methyltestosterone_MeSH S_adverse_effects_MeSH Methyltestosterone_adverse_effects_MeSH S_therapeutic_use_MeSH Methyltestosterone_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Quality_of_Life_MeSH M_Sex_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_Congeners_MeSH S_adverse_effects_MeSH Testosterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Testosterone_Congeners_therapeutic_use_MeSH M_Weight_Lifting_MeSH 
****** 11932287
----K E
----T Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents.
----A Some, but not all, antiresorptive agents have been shown to reduce the risk of nonvertebral fractures. Agents that significantly reduced nonvertebral fracture risk also appear to produce larger mean increases in bone mineral density (BMD) and reductions in biochemical markers (BCM) of bone turnover, compared with other agents. To examine the extent to which increases in BMD and reductions in BCM during antiresorptive therapy are associated with reductions in risk of nonvertebral fractures, we performed a meta-analysis of all randomized, placebo-controlled trials of antiresorptive agents conducted in postmenopausal women with osteoporosis (i.e. prior vertebral fracture or low BMD) with available relevant data. A total of 18 such trials with usable data were identified, including a total of 2,415 women with incident nonvertebral fractures over 69,369 women-years of follow-up. Poisson regression was used to estimate the association between changes in BMD or BCM during the first year and overall reductions in risk of nonvertebral fractures (vs. the placebo group) across all trials. Larger increases in BMD and larger reductions in BCM were significantly associated with greater reductions in nonvertebral fracture risk. For example, each 1% increase in spine BMD at 1 yr was associated with an 8% reduction in nonvertebral fracture risk (P = 0.02). Mean BMD changes at the hip were smaller than at the spine, but the predicted net effect on fracture risk was the same; an agent that increases spine BMD by 6% at 1 yr reduces nonvertebral fracture risk by about 39%, and an agent that increases hip BMD by 3% at 1 yr reduces nonvertebral fracture risk by about 46%. The results also predict that a 70% reduction in resorption BCM would reduce risk by 40%, and a 50% reduction in formation BCM would reduce risk by 44%. It appears that either BMD or BCM changes are able to explain the effect of treatment, because a separate variable for treatment was not independently significant in any models. These data demonstrate that larger increases in BMD at both the spine and hip and larger reductions in both formation and resorption BCM are associated with greater reductions in the risk of nonvertebral fractures. Antiresorptive agents that do not produce large increases in BMD or large reductions in BCM do not appear to and would not be expected to decrease the risk of nonvertebral fractures.
----P Journal_Article Meta-Analysis 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH P_Bone_Density_MeSH P_Bone_Remodeling_MeSH M_Bone_Resorption_MeSH S_drug_therapy_MeSH Bone_Resorption_drug_therapy_MeSH M_Female_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Incidence_MeSH M_Middle_Aged_MeSH M_Randomized_Controlled_Trials_MeSH 
****** 11934652
----K I
----T Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women.
----A The beneficial effects of hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), or bisphosphonates in the prevention and treatment of osteoporosis in postmenopausal women have been well established. However, little is known about the effects of discontinuation of treatment on bone mineral density. We investigated the effect of 1 year of discontinuation of the SERM raloxifene (Ral; 60 mg and 150 mg), conjugated equine estrogen (CEE; 0.625 mg), and placebo after 5 years of treatment in a double-blind, randomized study. Thirty-eight of 59 healthy and hysterectomized postmenopausal women (mean age 55 years) completed the treatment and 1 year follow-up period. Lumbar spine and femoral neck bone mineral density (BMD) were performed with dual-energy X-ray absorptiometry, before, during, and at the end of treatment, as well as after 1 year of discontinuation of therapy. One year of discontinuation significantly reduced the mean lumbar spine BMD in the raloxifene- and estrogen-treated women (p < 0.05), whereas mean femoral neck BMD was reduced significantly only in women treated with 60 mg Ral (p < 0.05). The mean percentage change (+/-SD) in lumbar spine BMD was: CEE, -6.2% (+/-3.7%); Ral 60 mg, -2.4% (+/-2.4%); Ral 150 mg, -2.6% (+/-3.1%); and placebo, -1.6% (+/-4.3%). Our results show that 5 years of treatment with either Ral or CEE did not protect against bone loss after 1 year of withdrawal of therapy, and that the rate of bone loss was not significantly different from that of placebo-treated women.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article Multicenter_Study 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Femur_Neck_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH M_Postmenopause_MeSH M_Raloxifene_MeSH S_administration_&_dosage_MeSH Raloxifene_administration_&_dosage_MeSH M_Selective_Estrogen_Receptor_Modulators_MeSH S_administration_&_dosage_MeSH Selective_Estrogen_Receptor_Modulators_administration_&_dosage_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11934658
----K E
----T Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent.
----A In this study we examine the influence of number of years since menopause on spontaneous bone loss and response to hormone replacement therapy (HRT) in 274 women (56.1 +/- 4.2 years) completing two placebo-controlled HRT studies of 2 or 3 year duration. Both cross sectionally and longitudinally, bone loss in untreated women was greatest closest to menopause and declined thereafter (r = 0.34, p < 0.01 for lumbar spine bone loss and r = 0.25, p < 0.05 for femoral neck bone loss when correlated with number of years since menopause), such that the loss was eliminated in the femoral neck and bone mass increased in the spine in women >10 years after menopause. In contrast, bone turnover was consistently elevated throughout postmenopause, both cross-sectionally and longitudinally. The association with number of years since menopause was counteracted by both 1 and 2 mg estradiol combined with gestodene, piperazine, estrone sulfate in combination with norethisterone, and a combination of 2 mg estradiol and 1 mg norethisterone acetate. In addition, the response to various HRT regimens was independent of baseline bone mass. Whereas bone loss was significantly related to number of years since menopause, all HRT regimens applied arrested bone loss in healthy postmenopausal women, regardless of number of years since menopause.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Age_Factors_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Cross-Sectional_Studies_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Norpregnenes_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH 
****** 11939671
----K I
----T Effects of period-free hormone replacement therapy in postmenopausal women in Taiwan.
----A BACKGROUND: To compare the effects of continuous combined hormone replacement therapy (Kliogest) and placebo on climacteric symptoms, bone turnover markers, serum lipid profiles and the safety of Kliogest. METHODS: This is a 4-month, single-centre, double-blind, placebo-controlled clinical study. Fifty-six healthy volunteer women with intact uterus, between six months and three years after a natural menopause, were recruited and randomised into two groups to have blood and urine laboratory test for assessment of bone resorption marker of deoxypyridinoline, bone formation marker of bone specific alkaline phosphatase, lipid profile including total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride, and menopausal symptoms. Information was taken at initial visit and 1, 2 and final follow-up after taking medication. RESULTS: Continuous Kliogest treatment resulted in significant reduction in menopausal symptoms, as scored by Integrated Greene Climacteric Scale and in the psychological, somatic and vasomotor subscales scores (p = 0.009). Kliogest reversed the negative trends in lipoprotein profiles by lowering total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001), and triglyceride (p = 0.004), but decreasing high-density lipoprotein cholesterol (p = 0.002). A significant reduction in bone resorption marker, deoxypyridinoline, was also observed in the Kliogest group (p < 0.001). There was no report of serious adverse events, endometrial hyperplasia or cancer in the Kliogest treated patients. CONCLUSIONS: Four-month treatment with Kliogest resulted in an improvement in menopausal symptoms and lipid profiles as well as reduction in bone loss.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH 
****** 11940375
----K E
----T Treatment of osteoporosis in men using dehydroepiandrosterone sulfate.
----A OBJECTIVE: To study the effect of dehydroepiandrosterone sulfate (DHEAS) treatment of osteoporosis in men with T(BMD) > or = 2.5SD. METHODS: Eighty-six patients were randomly divided into two groups: treatment group (n = 44) and control group (n = 42). DHEAS (100 mg q.d.) was given to the treatment group for 6 months. Bone mineral density, (BMD), biochemical markers of bone absorption and formation and other serum biochemical markers were measured before and after DHEAS treatment. Drug side effects were also evaluated. RESULTS: After oral administration of DHEAS (100 mg q.d.) for 6 months, the serum concentrations of DHEAS and IGF-I in the treatment group were 93.75% +/- 16.1% and 17.71% +/- 4.2% higher respectively than those in the control group (P < 0.01). The BMD of L2, L3, L4, L2 - 4 and Neck sections increased in the treatment group by 2.65% +/- 0.65%, 2.70% +/- 0.48%, 3.10% +/- 0.41%, 2.82% +/- 0.37% and 2.32% +/- 0.31%, respectively, as compared with that the control group (P < 0.05 or 0.01). No significant changes were observed in serum FT, E(2) and PSA concentrations in the treatment group as compared with the control group. CONCLUSION: The treatment of osteoporosis in men with DHEAS is safe and effective.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_therapeutic_use_MeSH Dehydroepiandrosterone_Sulfate_therapeutic_use_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH S_physiopathology_MeSH Osteoporosis_physiopathology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11973443
----K I
----T Safety and efficacy of a continuous once-a-week 17beta-estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials.
----A OBJECTIVE: Two prospective multicenter, double-blind, randomized, controlled trials were conducted to examine the safety and efficacy of three once-a-week continuous combined 17beta-estradiol/levonorgestrel (E2/LNG) transdermal systems (E2 0.045 mg/day with 0.015, 0.030, and 0.040 mg/day LNG) for the treatment of vasomotor symptoms and prevention of estrogen-induced endometrial hyperplasia in healthy, postmenopausal women. DESIGN: In study 1, performed in 293 hysterectomized and nonhysterectomized women with moderate to severe hot flushes, transdermal E2/LNG (E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG) was compared with placebo for three 28-day treatment cycles. The frequency and severity of hot flushes were recorded daily. In study 2, performed in 845 women with intact uteri, transdermal E2/LNG (E2 0.045 mg/day with 0.015, 0.030, and 0.040 mg/day LNG) was compared with transdermal E2 0.045 mg/day monotherapy for thirteen 28-day treatment cycles. Women with endometrial tissue sufficient for evaluation underwent endometrial biopsy assessment at the end of cycle 13. Bleeding patterns were assessed throughout the study, and the Women's Health Questionnaire was used to assess well-being. RESULTS: In study 1, transdermal E2/LNG (E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG) significantly decreased the number and severity of hot flushes when compared with placebo. Symptom relief was seen as early as 2 weeks posttreatment. Similarly, in study 2, all three doses of transdermal E2/LNG and E2 controlled hot flushes with no differences between groups. In study 2, no women receiving transdermal E2/LNG developed endometrial hyperplasia compared with 19 (12.8%) who received transdermal E2 0.045 mg/day (p < 0.001 for each dose). Significant improvements from baseline in scores on the Women's Health Questionnaire for vasomotor symptoms, sleep problems, sexual function, cognitive difficulties, and total score were noted at all or most time points with both transdermal E2/LNG and E2. Application-site reactions, vaginal hemorrhage, and breast pain were the most common adverse events reported with transdermal E2/LNG. The proportion of women with amenorrhea increased over time in all treatment groups in study 2. CONCLUSIONS: All three doses of this once-a-week combined E2/LNG transdermal system rapidly and effectively control vasomotor symptoms in postmenopausal women while protecting against endometrial hyperplasia. Amelioration of vasomotor symptoms also is accompanied by improvements in aspects of subjective well-being. Once-a-week transdermal E2/LNG, therefore, offers an effective and convenient formulation, the dosing of which can be individualized according to the needs of each patient.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Combinations_MeSH M_Endometrial_Hyperplasia_MeSH S_prevention_&_control_MeSH Endometrial_Hyperplasia_prevention_&_control_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH S_pharmacology_MeSH Levonorgestrel_pharmacology_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH 
****** 11974560
----K E
----T A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability.
----A OBJECTIVE: To compare the effects of continuous combined conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA) with those of tibolone on symptom control, bleeding pattern, lipid profile and tolerability in postmenopausal women. METHODS: This was a randomized, open-label, parallel-group, multicenter study. Generally healthy postmenopausal women with an intact uterus and no contraindications to hormone replacement therapy (HRT) or tibolone were enrolled. Each subject was randomly assigned to receive CEE/MPA 0.625 mg-5.0 mg or tibolone 2.5 mg daily for 13 treatment cycles, each of 28 days. RESULTS: A total of 85 subjects were enrolled and received at least one dose of study medication, of which 76 (89.4%) subjects completed the study (n = 40, CEE/MPA; n = 36, tibolone). The incidence of postmenopausal symptoms decreased significantly over time in both treatment groups, compared with baseline, including significant decreases in the incidence of urogenital and sexual health symptoms. Significant differences in symptom control (other than hot flushes) were observed between treatment groups in a few different cycles for different symptoms, but no consistent or clinically significant trends were observed. No statistically significant differences in the incidence of bleeding were observed between treatment groups after cycle 4. Significant decreases in total cholesterol (5.6%) and low-density lipoprotein (LDL) cholesterol (7.5%) were observed at cycle 13, compared with baseline, in the CEE/MPA group, and significant decreases in high-density lipoprotein (HDL) cholesterol (8.5%) and triglycerides (13.7%) were observed at cycle 13, compared with baseline, in the tibolone group. Significant weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared with the CEE/MPA group (0.96 kg). The incidences of adverse events were similar in both treatment groups. CONCLUSIONS: Women treated with CEE/MPA or tibolone showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms, and had similar bleeding patterns after four cycles of therapy. CEE/MPA and tibolone each induced a different mix of changes in the lipid profile.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Animals_MeSH M_Coitus_MeSH M_Comparative_Study_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Horses_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH S_adverse_effects_MeSH Norpregnenes_adverse_effects_MeSH P_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Urogenital_Diseases_MeSH S_prevention_&_control_MeSH Urogenital_Diseases_prevention_&_control_MeSH M_Uterine_Hemorrhage_MeSH M_Weight_Gain_MeSH 
****** 11978277
----K E
----T Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
----A OBJECTIVE: To assess post-treatment effects in endometriosis patients of a 12-month course of GnRH agonist alone or with one of three "add-back" regimens. METHODS: This is a post-treatment follow-up analysis of a randomized, double-masked, placebo-controlled 52-week trial. All patients had received monthly leuprolide acetate and were randomized to one of four groups: A-daily placebo; B-daily norethindrone acetate 5 mg; C-daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg; and D-daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial, 123 completed at least 280 days of therapy and entered the follow-up period. Physical findings and symptoms were quantified, and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post-therapy. RESULTS: Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups (P <.05). Findings were not affected by endometriosis scores noted on screening laparoscopy. Mean bone mineral density values remained at or above baseline in all add-back groups. The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow-up visit (P <.001). CONCLUSION: GnRH agonist and norethindrone acetate alone or combined with low-dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Delayed-Action_Preparations_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Therapy__Combination_MeSH M_Endometriosis_MeSH S_drug_therapy_MeSH Endometriosis_drug_therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Gonadorelin_MeSH S_agonists_MeSH Gonadorelin_agonists_MeSH M_Human_MeSH M_Leuprolide_MeSH S_administration_&_dosage_MeSH Leuprolide_administration_&_dosage_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Patient_Dropouts_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 11991445
----K E
----T Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss.
----A In this 2-year, randomized study, we compared the efficacy and tolerability of tibolone 2.5 mg (n = 75), tibolone 1.25 mg (n = 76) and estradiol 2 mg plus norethindrone acetate 1 mg (E2/NETA: n = 74) for preventing bone loss in postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed every 6 months. Side-effects were assessed quarterly. After 24 months, the mean increase (+/- SD) in lumbar spine BMD from baseline was 3.6% +/- 2.9%, 1.9% +/- 3.5% and 6.8% +/- 4.5% in the tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA groups, respectively. All pairwise differences were significant. The proportion of responders (women with a change from baseline in lumbar spine BMD of > or = -2% after 2 years) was 95.7%, 89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA, respectively. Similar results were obtained for femoral BMD, although the difference between tibolone 2.5 mg and E2/NETA was not significant at 24 months. Decreases in bone remodeling markers were similar in the three groups. Vaginal bleeding was more common in the E2/ NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively). Each treatment effectively prevented bone loss. Overall, tolerability of tibolone was better than with E2/NETA, because of less frequent vaginal bleeding and breast pain. This may promote long-term adherence.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Androgen_Antagonists_MeSH S_adverse_effects_MeSH Androgen_Antagonists_adverse_effects_MeSH S_therapeutic_use_MeSH Androgen_Antagonists_therapeutic_use_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Breast_MeSH M_Calcium_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Norpregnenes_MeSH S_adverse_effects_MeSH Norpregnenes_adverse_effects_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Pain_MeSH S_chemically_induced_MeSH Pain_chemically_induced_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Statistics__Nonparametric_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH 
****** 12014437
----K E
----T Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women.
----A BACKGROUND: Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-alpha (ER alpha) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women. METHOD: We studied the influence of the ER alpha genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ER alpha gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ER alpha genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ER alpha genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ER alpha genotype. In conclusion, ER alpha polymorphism is associated with fall risk, especially with non-slip falls, in early postmenopausal Finnish women during the HRT. We have previously reported that, during HRT, women with the P allele have decreased fracture risk and that they may preferentially derive benefit from the positive effect of HRT on BMD. This suggests that the influence of ER alpha polymorphism may depend on the target tissue (bone versus the nervous system). CONCLUSIONS: In these early postmenopausal, non-osteoporotic and relatively healthy women, the increased fall risk associated with the PP genotype was not associated with increased fracture risk, possibly due to improved bone strength during the HRT although falls generally predispose to fractures.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Accidental_Falls_MeSH S_prevention_&_control_MeSH Accidental_Falls_prevention_&_control_MeSH M_Age_Factors_MeSH M_Aged_MeSH M_Bone_Density_MeSH S_genetics_MeSH Bone_Density_genetics_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Densitometry_MeSH M_Female_MeSH M_Finland_MeSH M_Fractures__Spontaneous_MeSH S_epidemiology_MeSH Fractures__Spontaneous_epidemiology_MeSH S_genetics_MeSH Fractures__Spontaneous_genetics_MeSH M_Hand_Strength_MeSH S_physiology_MeSH Hand_Strength_physiology_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_diagnosis_MeSH Osteoporosis__Postmenopausal_diagnosis_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_genetics_MeSH Osteoporosis__Postmenopausal_genetics_MeSH P_Polymorphism_(Genetics)_MeSH M_Probability_MeSH M_Receptors__Estrogen_MeSH S_analysis_MeSH Receptors__Estrogen_analysis_MeSH S_genetics_MeSH Receptors__Estrogen_genetics_MeSH M_Reference_Values_MeSH M_Risk_Assessment_MeSH M_Risk_Factors_MeSH M_Sensitivity_and_Specificity_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12020302
----K I
----T Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women.
----A CONTEXT: Lower-than-commonly-prescribed doses of conjugated equine estrogens (CEEs) with medroxyprogesterone acetate (MPA) improve vasomotor symptoms and vaginal atrophy, provide acceptable bleeding and lipid profiles, and afford endometrial protection. This lower-dose therapy's protection against loss of bone mineral density (BMD) associated with menopause has not been thoroughly investigated. OBJECTIVE: To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD, total body bone mineral content (BMC), and biochemical markers of bone turnover in postmenopausal women. DESIGN AND SETTING: Two-year randomized, double-blind, placebo-controlled substudy of the Women's Health, Osteoporosis, Progestin, Estrogen trial, conducted at 19 US centers between August 1995 and October 2000. PARTICIPANTS: Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period. INTERVENTIONS: Patients were randomly assigned to receive CEEs, 0.625; CEEs, 0.625 and MPA, 2.5; CEEs, 0.45; CEEs, 0.45 and MPA, 2.5; CEEs, 0.45 and MPA, 1.5; CEEs, 0.3; CEEs 0.3 and MPA, 1.5 (all doses in mg/d); or placebo for 2 years. All participants also received elemental calcium at 600 mg/d. MAIN OUTCOME MEASURES: Changes from baseline in spine and total hip BMD, total body BMC, and biochemical markers of bone turnover (serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen), assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach. RESULTS: At 24 months, women assigned to all of the active treatment groups had significant gains from baseline (P<.001) in spine and hip BMD and total body BMC (except total body BMC in the group receiving CEEs, 0.3 mg/d). These changes were significantly different from those in the placebo group, in which losses of bone mass in spine and total body were evident over the course of the study (P<.001). The loss in hip BMD from baseline in the placebo group was significant at 18 (P =.02) but not at 24 months (P =.06). Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline (P<.001) for all active treatment groups at all time points; no changes were found for the placebo group. For women treated with CEEs alone, the gains in spine BMD for the group taking CEEs, 0.625 mg/d, were significantly higher than those of the group taking CEEs, 0.3 mg/d (P =.02), but not the group treated with CEEs, 0.45 mg/d (P =.48). CONCLUSIONS: Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Biological_Markers_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Middle_Aged_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12036821
----K E
----T Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women.
----A BACKGROUND: Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly. Other nutrients also affect bone health, and adequate intakes may influence bone turnover and balance. OBJECTIVE: We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement, a calcium and vitamin D supplement, and dietary instruction aimed at increasing calcium intake through foods. DESIGN: Ninety-nine healthy postmenopausal women participated in a 3-y, randomized trial, receiving either 1) supplemental calcium (1450 mg/d) and vitamin D [10 microg (400 IU)/d], 2) calcium, vitamin D, and other nutrients (multinutrient supplement), or 3) dietary instruction (dietary control group). Data are from 83 subjects who completed the trial. RESULTS: Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups. Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter. Bone turnover markers followed a similar pattern, and none of the changes in biochemical concentrations differed significantly between groups. CONCLUSIONS: All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations. The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone. The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH S_physiology_MeSH Bone_Remodeling_physiology_MeSH M_Calcium_MeSH S_blood_MeSH Calcium_blood_MeSH M_Calcium__Dietary_MeSH S_administration_&_dosage_MeSH Calcium__Dietary_administration_&_dosage_MeSH S_metabolism_MeSH Calcium__Dietary_metabolism_MeSH M_Diet_MeSH M_Dietary_Supplements_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Parathyroid_Hormone_MeSH S_secretion_MeSH Parathyroid_Hormone_secretion_MeSH M_Patient_Compliance_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vitamin_D_MeSH S_administration_&_dosage_MeSH Vitamin_D_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Vitamin_D_analogs_&_derivatives_MeSH S_blood_MeSH Vitamin_D_blood_MeSH S_metabolism_MeSH Vitamin_D_metabolism_MeSH 
****** 12047395
----K E
----T Cardiovascular effects of raloxifene: the potential for cardiovascular protection in women.
----A 
----P Journal_Article Review Review__Tutorial 
----M M_Cardiovascular_System_MeSH S_drug_effects_MeSH Cardiovascular_System_drug_effects_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH S_physiology_MeSH Endothelium__Vascular_physiology_MeSH M_Estrogen_Antagonists_MeSH S_pharmacology_MeSH Estrogen_Antagonists_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Muscle__Smooth__Vascular_MeSH S_drug_effects_MeSH Muscle__Smooth__Vascular_drug_effects_MeSH S_physiology_MeSH Muscle__Smooth__Vascular_physiology_MeSH M_Nitric_Oxide_MeSH S_physiology_MeSH Nitric_Oxide_physiology_MeSH M_Postmenopause_MeSH M_Raloxifene_MeSH S_pharmacology_MeSH Raloxifene_pharmacology_MeSH 
****** 12051113
----K E
----T Endometrial safety of a transdermal sequential estradiol-levonorgestrel combination.
----A OBJECTIVE: The aim of this 1-year, randomized, multinational, open-label study was to assess the effect on the endometrium of three dosages of estradiol and sequential levonorgestrel, each administered in a novel 7-day transdermal matrix patch. METHODS: A total of 468 postmenopausal women received patches of 15 cm2 (50 micrograms/day estradiol for 2 weeks followed by 50 micrograms/day estradiol-10 micrograms/day levonorgestrel for 2 weeks), 22.5 cm2 (75 micrograms/day estradiol for 2 weeks followed by 75 micrograms/day estradiol-15 micrograms/day levonorgestrel for 2 weeks) or 30 cm2 (100 micrograms/day estradiol for 2 weeks followed by 100 micrograms/day estradiol-20 micrograms/day levonorgestrel for 2 weeks). Each patch was applied for 7 days. RESULTS: Endometrial biopsies were taken before and after 1 year of treatment, with final valid biopsy results being obtained in 399 women. There were two cases of endometrial hyperplasia (one in the 22.5-cm2 and one in the 30-cm2 group). All three doses of this 7-day sequential combined estradiol-levonorgestrel transdermal hormone replacement therapy therefore had excellent endometrial safety. The lowest dose, however, was associated with less bleeding and a somewhat different histological pattern, compared with the two higher doses. All three doses provided a high level of patient satisfaction with the bleeding response. CONCLUSION: Estradiol and sequential levonorgestrel administered in a 7-day transdermal matrix patch for 1 year provide endometrial protection.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Drug_Administration_Schedule_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Germany_MeSH M_Great_Britain_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH S_pharmacology_MeSH Levonorgestrel_pharmacology_MeSH M_Middle_Aged_MeSH M_Netherlands_MeSH P_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12076241
----K I
----T Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized, double-blind, placebo-controlled trial.
----A BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass. METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo. All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (800 IU/d) supplements. The primary efficacy end points were the changes in alveolar crest height and alveolar bone density. Alveolar crest height was measured on bite-wing radiographs, and changes in alveolar bone mass were assessed by means of digital-subtraction radiography. Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry. RESULTS: Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo (+1.84% vs +0.95% [P =.04]), and tended to improve alveolar crest height (+4.83% vs +3.46% [P =.34]). Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group (total proximal femur, +3.59% vs +0.22% [P =.001]; neck, +2.05% vs -0.34% [P =.02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P =.39]). Changes in alveolar bone mass correlated with bone density changes in the total femur (r = 0.28 [P =.02]) and femoral trochanter (r = 0.25 [P =.04]) in the H/ERT but not in the placebo group. CONCLUSIONS: Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT. Improvement in oral bone health constitutes an additional benefit of H/ERT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Alveolar_Bone_Loss_MeSH S_prevention_&_control_MeSH Alveolar_Bone_Loss_prevention_&_control_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Densitometry__X-Ray_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Femur_MeSH S_physiopathology_MeSH Femur_physiopathology_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_physiopathology_MeSH Lumbar_Vertebrae_physiopathology_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Multivariate_Analysis_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12082358
----K E
----T Cognitive function effects of suppressing ovarian hormones in young women.
----A OBJECTIVE: To evaluate the effect of a pharmacologically induced, temporary suppression of ovarian hormones on healthy young women's cognitive functioning. DESIGN: Sixteen healthy women with normal menstrual cycles completed the California Verbal Learning Test, a digit span test, and a verbal fluency test in the follicular phase of a normal menstrual cycle and a second time after four monthly injections of the gonadotropin-releasing hormone (GnRH) agonist. Women were randomly assigned to complete a third testing either after resuming cycles in the follicular phase or after three more injections of the GnRH agonist and while wearing an estradiol patch. The control group consisted of 10 women who were tested three times in the follicular phase of their menstrual cycles. RESULTS: Results showed no change in cognitive functioning across sessions or groups in women with suppressed ovarian function. Women who had the highest levels of menopausal symptoms when taking the GnRH agonist did not have significantly lower cognitive functioning. CONCLUSIONS: This study did not find any effect of suppression in ovarian hormones on cognitive performance of young women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Analysis_of_Variance_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Comparative_Study_MeSH M_Delayed-Action_Preparations_MeSH S_administration_&_dosage_MeSH Delayed-Action_Preparations_administration_&_dosage_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Gonadorelin_MeSH S_antagonists_&_inhibitors_MeSH Gonadorelin_antagonists_&_inhibitors_MeSH M_Human_MeSH M_Intelligence_Tests_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Menstrual_Cycle_MeSH S_drug_effects_MeSH Menstrual_Cycle_drug_effects_MeSH S_physiology_MeSH Menstrual_Cycle_physiology_MeSH M_Probability_MeSH M_Reference_Values_MeSH M_Sensitivity_and_Specificity_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12082361
----K E
----T Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women.
----A OBJECTIVE: To compare the mood and somatic effects during the initial 2 months of medroxyprogesterone acetate (MPA) or progesterone combined with conjugated equine estrogen (CEE) in early postmenopausal women. DESIGN: Twenty-three nondepressed, early postmenopausal women (average age, 52.5 years) completed a 91-day, single-blind pilot study with the following sequence of treatments: 1 week of no substance; 2 weeks of placebo; 2 weeks of progestogen only; 1 week of placebo; and 2 months of "standard hormone replacement therapy cycles," which consisted of (in order) 2 weeks of 0.625 mg CEE, 2 weeks of CEE plus progestogen, 2 weeks of CEE, and 2 weeks of CEE plus progestogen. Ten women who completed the study received MPA (5 mg/day) as their progestogen, and 13 who completed the study received micronized, oil-suspended progesterone (200 mg/day) as their progestogen. All participants made daily assessments of mood using the Profile of Mood States and daily recordings of somatic symptoms. All subjects had plasma follicle-stimulating hormone of greater than 35 IU/L and had not had spontaneous vaginal bleeding for more than 1 year. RESULTS: None of the hormone treatments had a detectable effect on mood. MPA users reported more vaginal bleeding and breast tenderness than progesterone users. CONCLUSIONS: In contrast with the widely held belief among psychiatrists that progesterone depresses mood, neither of the progestogens we used in normal, nondepressed and nonanxious women showed this effect. Absence of an effect on mood was also found when the results of the two progestogens were combined. The lesser side effects of the micronized progesterone-containing regimen suggest that some women may prefer it to an MPA-containing regimen.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Breast_MeSH S_physiopathology_MeSH Breast_physiopathology_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Administration_Schedule_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_physiopathology_MeSH Hot_Flashes_physiopathology_MeSH M_Human_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_adverse_effects_MeSH M_Middle_Aged_MeSH M_Mood_Disorders_MeSH S_physiopathology_MeSH Mood_Disorders_physiopathology_MeSH M_Physical_Fitness_MeSH M_Pilot_Projects_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH M_Probability_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_adverse_effects_MeSH M_Reference_Values_MeSH M_Sensitivity_and_Specificity_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12091203
----K E
----T Estrogen therapy and noncognitive psychiatric signs and symptoms in elderly patients with dementia.
----A OBJECTIVE: This study investigated the efficacy and safety of short-term estrogen therapy in decreasing noncognitive signs and symptoms of dementia in demented elderly patients. METHOD: Sixteen moderately to severely demented elderly patients with aggressive behavioral disturbances were randomly assigned to receive conjugated equine estrogens or placebo in a 4-week clinical trial. Frequency and severity of noncognitive signs and symptoms of dementia, as assessed with the Dementia Signs and Symptoms Scale, were compared between estrogen and placebo groups. Data were analyzed with intent-to-treat and regression modeling methods. RESULTS: Estrogen therapy was associated with a significantly greater improvement on the Dementia Signs and Symptoms Scale total score than placebo. All five Dementia Signs and Symptoms Scale subscale comparisons favored estrogen therapy. No adverse effects were observed. CONCLUSIONS: These preliminary data suggest that short-term estrogen therapy may safely decrease the frequency and severity of noncognitive signs and symptoms of dementia in elderly patients.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Age_Factors_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Aggression_MeSH S_psychology_MeSH Aggression_psychology_MeSH M_Comorbidity_MeSH M_Comparative_Study_MeSH M_Dementia_MeSH S_diagnosis_MeSH Dementia_diagnosis_MeSH S_drug_therapy_MeSH Dementia_drug_therapy_MeSH S_epidemiology_MeSH Dementia_epidemiology_MeSH S_psychology_MeSH Dementia_psychology_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH M_Placebos_MeSH M_Psychiatric_Status_Rating_Scales_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Treatment_Outcome_MeSH 
****** 12090862
----K I
----T Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).
----A CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) found no overall reduction in risk of coronary heart disease (CHD) events among postmenopausal women with CHD. However, in the hormone group, findings did suggest a higher risk of CHD events during the first year, and a decreased risk during years 3 to 5. OBJECTIVE: To determine if the risk reduction observed in the later years of HERS persisted and resulted in an overall reduced risk of CHD events with additional years of follow-up. DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted at outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380), or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group, and increased from 0% (year 1) to 8% (year 6) in the placebo group. MAIN OUTCOME MEASURES: The primary outcome was nonfatal myocardial infarction and CHD death. Secondary cardiovascular events were coronary revascularization, hospitalization for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia, sudden death, stroke or transient ischemic attack, and peripheral arterial disease. RESULTS: There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS II, or overall. The unadjusted relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19). CONCLUSIONS: Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aspirin_MeSH S_therapeutic_use_MeSH Aspirin_therapeutic_use_MeSH M_Coronary_Disease_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Hydroxymethylglutaryl-CoA_Reductase_Inhibitors_MeSH S_therapeutic_use_MeSH Hydroxymethylglutaryl-CoA_Reductase_Inhibitors_therapeutic_use_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Myocardial_Infarction_MeSH S_epidemiology_MeSH Myocardial_Infarction_epidemiology_MeSH M_Postmenopause_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH M_Survival_Analysis_MeSH M_Treatment_Outcome_MeSH 
****** 12090863
----K I
----T Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).
----A CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized trial of estrogen plus progestin therapy after menopause. OBJECTIVE: To examine the effect of long-term postmenopausal hormone therapy on common noncardiovascular disease outcomes. DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent open-label observational follow-up for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 postmenopausal women with coronary disease and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group and increased from 0% (year 1) to 8% (year 6) in the placebo group. MAIN OUTCOME MEASURES: Thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality. RESULTS: Comparing women assigned to hormone therapy with those assigned to placebo, the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and 3 of the 73 women with thromboembolism died within 30 days due to pulmonary embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses did not alter our conclusions. CONCLUSIONS: Treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery. Trends in other disease outcomes were not favorable and should be assessed in larger trials and in broader populations.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Biliary_Tract_Diseases_MeSH S_epidemiology_MeSH Biliary_Tract_Diseases_epidemiology_MeSH S_surgery_MeSH Biliary_Tract_Diseases_surgery_MeSH M_Biliary_Tract_Surgical_Procedures_MeSH S_statistics_&_numerical_data_MeSH Biliary_Tract_Surgical_Procedures_statistics_&_numerical_data_MeSH M_Cause_of_Death_MeSH P_Coronary_Disease_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Neoplasms_MeSH S_epidemiology_MeSH Neoplasms_epidemiology_MeSH M_Postmenopause_MeSH M_Pulmonary_Embolism_MeSH S_epidemiology_MeSH Pulmonary_Embolism_epidemiology_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH M_Survival_Analysis_MeSH M_Thromboembolism_MeSH S_epidemiology_MeSH Thromboembolism_epidemiology_MeSH M_Treatment_Outcome_MeSH M_Venous_Thrombosis_MeSH S_epidemiology_MeSH Venous_Thrombosis_epidemiology_MeSH 
****** 12102671
----K E
----T Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women.
----A PURPOSE: This study was designed to evaluate whether levetiracetam, a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives. METHODS: During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either levetiracetam, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase. RESULTS: The plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either levetiracetam or placebo. The ratios of the log-transformed geometric mean areas under the plasma concentration-time curves (AUCs), maximal (Cmax) and minimal (Cmin) plasma concentrations, and trough concentrations on day 21 (C21) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during levetiracetam and placebo administration. CONCLUSIONS: Levetiracetam does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Anticonvulsants_MeSH S_pharmacology_MeSH Anticonvulsants_pharmacology_MeSH M_Comparative_Study_MeSH M_Contraceptives__Oral__Synthetic_MeSH S_pharmacokinetics_MeSH Contraceptives__Oral__Synthetic_pharmacokinetics_MeSH M_Drug_Interactions_MeSH M_Ethinyl_Estradiol_MeSH S_blood_MeSH Ethinyl_Estradiol_blood_MeSH S_pharmacokinetics_MeSH Ethinyl_Estradiol_pharmacokinetics_MeSH M_Ethinyl_Estradiol-Norgestrel_Combination_MeSH S_blood_MeSH Ethinyl_Estradiol-Norgestrel_Combination_blood_MeSH S_pharmacokinetics_MeSH Ethinyl_Estradiol-Norgestrel_Combination_pharmacokinetics_MeSH M_Female_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_blood_MeSH Levonorgestrel_blood_MeSH S_pharmacokinetics_MeSH Levonorgestrel_pharmacokinetics_MeSH M_Piracetam_MeSH S_analogs_&_derivatives_MeSH Piracetam_analogs_&_derivatives_MeSH S_pharmacology_MeSH Piracetam_pharmacology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12107206
----K E
----T Cognitive effects of short-term manipulation of serum sex steroids in healthy young men.
----A We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 microg daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 microg daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Contraceptive_Agents__Male_MeSH S_administration_&_dosage_MeSH Contraceptive_Agents__Male_administration_&_dosage_MeSH S_pharmacology_MeSH Contraceptive_Agents__Male_pharmacology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Human_MeSH M_Injections__Intramuscular_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH S_pharmacology_MeSH Levonorgestrel_pharmacology_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Neuropsychological_Tests_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Testosterone_analogs_&_derivatives_MeSH S_blood_MeSH Testosterone_blood_MeSH S_pharmacology_MeSH Testosterone_pharmacology_MeSH M_Time_Factors_MeSH 
****** 12113884
----K E
----T A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium.
----A OBJECTIVE: This study was designed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy, to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms, and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology.METHODS: We performed a prospective, double-blinded, randomized, placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplementation versus placebo in postmenopausal women. Baseline endometrial biopsies were performed and, if adequate, nonhyperplastic, noncancerous, and nonovulatory, subjects were randomly assigned to receive daily placebo or soy cereal supplementation for 6 months. Study subjects completed baseline and weekly dietary, symptom, and side effect logs. Repeat endometrial biopsies were obtained at 6 months.RESULTS: Subjects were recruited from January 1998 through June 2000. Twenty-seven subjects were randomized, and 19 completed the study. One (3.7%) baseline endometrial sample was weakly proliferative. All other baseline and final biopsies were consistent with atrophic, inactive endometrium. The maximum risk of endometrial stimulation with phytoestrogens is 35%. Hot flushes, night sweats, and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group. Insomnia was more common in the treated group. There were no other statistically significant differences in symptoms or side effects.CONCLUSION: Phytoestrogens did not cause stimulation of the endometrium. Insomnia was more frequent over the 6-month study in the soy group, whereas hot flushes, night sweats, and vaginal dryness improved from baseline in the placebo group but not in the soy group.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Biopsy_MeSH P_Diet_MeSH M_Double-Blind_Method_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estrogens__Non-Steroidal_MeSH S_administration_&_dosage_MeSH Estrogens__Non-Steroidal_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Non-Steroidal_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_therapy_MeSH Hot_Flashes_therapy_MeSH M_Human_MeSH P_Isoflavones_MeSH M_Middle_Aged_MeSH M_Pilot_Projects_MeSH M_Placebos_MeSH M_Plant_Preparations_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Soybeans_MeSH S_chemistry_MeSH Soybeans_chemistry_MeSH M_Sweating_MeSH S_drug_effects_MeSH Sweating_drug_effects_MeSH M_Vaginal_Diseases_MeSH S_therapy_MeSH Vaginal_Diseases_therapy_MeSH 
****** 12117397
----K I
----T Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
----A CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH S_prevention_&_control_MeSH Breast_Neoplasms_prevention_&_control_MeSH M_Cerebrovascular_Accident_MeSH S_epidemiology_MeSH Cerebrovascular_Accident_epidemiology_MeSH M_Clinical_Trials_Data_Monitoring_Committees_MeSH M_Colorectal_Neoplasms_MeSH S_epidemiology_MeSH Colorectal_Neoplasms_epidemiology_MeSH M_Coronary_Disease_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Endometrial_Neoplasms_MeSH S_epidemiology_MeSH Endometrial_Neoplasms_epidemiology_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Myocardial_Infarction_MeSH S_epidemiology_MeSH Myocardial_Infarction_epidemiology_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Proportional_Hazards_Models_MeSH M_Pulmonary_Embolism_MeSH S_epidemiology_MeSH Pulmonary_Embolism_epidemiology_MeSH M_Risk_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Survival_Analysis_MeSH M_Thrombosis_MeSH S_epidemiology_MeSH Thrombosis_epidemiology_MeSH M_Treatment_Outcome_MeSH 
****** 12117398
----K I
----T Menopausal hormone replacement therapy and risk of ovarian cancer.
----A CONTEXT: The association between menopausal hormone replacement therapy and ovarian cancer is unclear. OBJECTIVE: To determine whether hormone replacement therapy using estrogen only, estrogen-progestin only, or both estrogen only and estrogen-progestin increases ovarian cancer risk. DESIGN: A 1979-1998 cohort study of former participants in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine US clinical centers. PARTICIPANTS: A total of 44 241 postmenopausal women (mean age at start of follow-up, 56.6 years). MAIN OUTCOME MEASURE: Incident ovarian cancer. RESULTS: We identified 329 women who developed ovarian cancer during follow-up. In time-dependent analyses adjusted for age, menopause type, and oral contraceptive use, ever use of estrogen only was significantly associated with ovarian cancer (rate ratio [RR], 1.6; 95% confidence interval [CI], 1.2-2.0). Increasing duration of estrogen-only use was significantly associated with ovarian cancer: RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and 3.2 (95% CI, 1.7-5.7), respectively (P value for trend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR per year of use. We observed significantly elevated RRs with increasing duration of estrogen-only use across all strata of other ovarian cancer risk factors, including women with hysterectomy. The RR for estrogen-progestin use after prior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin-only use was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or more years of estrogen-progestin-only use were 1.6 (95% CI, 0.78-3.3) and 0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a duration response (P value for trend =.30). CONCLUSION: Women who used estrogen-only replacement therapy, particularly for 10 or more years, were at significantly increased risk of ovarian cancer in this study. Women who used short-term estrogen-progestin-only replacement therapy were not at increased risk, but risk associated with short-term and longer-term estrogen-progestin replacement therapy warrants further investigation.
----P Journal_Article Multicenter_Study 
----M M_Aged_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Hysterectomy_MeSH M_Likelihood_Functions_MeSH M_Middle_Aged_MeSH M_Ovarian_Neoplasms_MeSH S_epidemiology_MeSH Ovarian_Neoplasms_epidemiology_MeSH M_Poisson_Distribution_MeSH M_Progestins_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Risk_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Time_Factors_MeSH 
****** 12125806
----K E
----T Hormone replacement therapy: current concerns and considerations.
----A AUDIENCE: This activity is designed for pharmacists and other healthcare professionals who evaluate and treat perimenopausal and postmenopausal women. GOALS: To understand the benefits, risks, and adverse effects associated with estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) and their influence on a postmenopausal woman's initiation, adherence, and satisfaction with therapy. OBJECTIVES: 1. Discuss menopause and its effects. 2. Identify ERT/HRT's potential benefits and risks. 3. Discuss ERT/HRT's adverse effects and management approaches. 4. Identify various administration routes for ERT/H RT. 5. Identify currently available ERT/HRT products. 6. Recognize potential reasons for lack of initiation and continuation as well as ways to improve adherence in patients.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Decision_Making_MeSH M_Education__Pharmacy__Continuing_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_classification_MeSH Estrogens_classification_MeSH S_economics_MeSH Estrogens_economics_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_classification_MeSH Progesterone_classification_MeSH S_economics_MeSH Progesterone_economics_MeSH M_Risk_Assessment_MeSH M_United_States_MeSH 
****** 12130763
----K E
----T Women's health. The vanishing promises of hormone replacement.
----A 
----P News 
----M M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH M_Cardiovascular_Diseases_MeSH S_epidemiology_MeSH Cardiovascular_Diseases_epidemiology_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Colorectal_Neoplasms_MeSH S_epidemiology_MeSH Colorectal_Neoplasms_epidemiology_MeSH S_prevention_&_control_MeSH Colorectal_Neoplasms_prevention_&_control_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Menopause_MeSH M_Postmenopause_MeSH M_Pulmonary_Embolism_MeSH S_epidemiology_MeSH Pulmonary_Embolism_epidemiology_MeSH P_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH M_Selection_Bias_MeSH M_Time_Factors_MeSH 
****** 12153335
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----T Spotlight on ziprasidone in schizophrenia and schizoaffective disorder.
----A Ziprasidone is a novel antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical antipsychotics. In preclinical studies, ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. The drug has been administered orally to >300 patients with an acute exacerbation of schizophrenia or schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily at dosages of between 80 and 160 mg/day, ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study, ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day. Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic schizophrenia who were treated for up to 1 year. In addition, significantly more ziprasidone than haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic schizophrenia. In general, oral ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the drug has a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The drug does not appear to be associated with sustained elevation of plasma prolactin levels. Preliminary data indicate that long-term oral ziprasidone treatment is well tolerated. Ziprasidone is the only novel antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular ziprasidone was effective and well tolerated in patients with acute agitation associated with psychosis. In addition, intramuscular ziprasidone reduced agitation scores by a significantly greater extent than haloperidol in a study involving patients with acute agitation associated with psychosis. CONCLUSIONS: Ziprasidone is a promising new antipsychotic that has shown significant efficacy in the oral treatment of patients with schizophrenia or schizoaffective disorder. The drug is well tolerated with a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and good tolerability in the treatment of acute agitation associated with psychotic disorders.
----P Journal_Article Review Review__Tutorial 
----M M_Antipsychotic_Agents_MeSH S_administration_&_dosage_MeSH Antipsychotic_Agents_administration_&_dosage_MeSH S_pharmacology_MeSH Antipsychotic_Agents_pharmacology_MeSH S_therapeutic_use_MeSH Antipsychotic_Agents_therapeutic_use_MeSH M_Human_MeSH M_Piperazines_MeSH S_administration_&_dosage_MeSH Piperazines_administration_&_dosage_MeSH S_pharmacology_MeSH Piperazines_pharmacology_MeSH S_therapeutic_use_MeSH Piperazines_therapeutic_use_MeSH M_Psychotic_Disorders_MeSH S_drug_therapy_MeSH Psychotic_Disorders_drug_therapy_MeSH M_Randomized_Controlled_Trials_MeSH M_Schizophrenia_MeSH S_drug_therapy_MeSH Schizophrenia_drug_therapy_MeSH M_Thiazoles_MeSH S_administration_&_dosage_MeSH Thiazoles_administration_&_dosage_MeSH S_pharmacology_MeSH Thiazoles_pharmacology_MeSH S_therapeutic_use_MeSH Thiazoles_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
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----T Effect of methyl testosterone administration on plasma viscosity in postmenopausal women.
----A BACKGROUND: Coronary heart disease (CHD) is the leading cause of mortality in women, with an incidence that increases after menopause, hence suggesting a cardioprotective role of oestrogen. Menopause also results in a decline in androgen levels with resulting symptoms of decreased libido and sexual dysfunction. Recently, there has been a growing interest in the treatment of postmenopausal women with androgens. However, no data are available on plasma viscosity and fibrinogen levels in postmenopausal women on combined oestrogen/androgen therapy. METHODS: We conducted a randomized, double-blind, parallel-group 16-week study evaluating the effects of methyltestosterone supplementation on plasma viscosity and fibrinogen levels in postmenopausal women already on oestrogen replacement therapy (ERT) for at least 3 months. Women 21 years and older who were menopausal (natural or surgical) for at least 12 months were enrolled in the study. Participants were randomized to (1) an oestrogen-only group taking 1.25 mg esterified oestrogen (E-group) and (2) an oestrogen plus methyltestosterone (1.25 mg esterified oestrogen and 2.5 mg methyltestosterone) group (EA-group). Progesterone was not administered during the study period and women with intact uteri were given medroxyprogesterone 10 mg daily for 14 days at the completion of the study. RESULTS: After 16 weeks of treatment, both groups had a significant increase in serum oestradiol levels from baseline. The levels of total oestrogen were significantly higher in the E-group compared to the EA-group (P < 0.001). There was a greater decrease in the LH and SHBG levels in the EA-group (P = 0.01). There was no difference in total testosterone; however, free testosterone levels were significantly higher in the EA-group (P = 0.01). At the end of the study, there was a significant decrease in plasma viscosity only in the EA-group (P = 0.01). Fibrinogen levels increased in both the groups, reaching significance only in the EA-group (P = 0.006). Baseline weight, body mass index (BMI) and the duration of menopausal status did not have any significant impact on the changes in plasma viscosity or fibrinogen. Women in the EA-group showed significant reductions in total cholesterol (P = 0.009), high density lipoprotein (HDL) (P < 0.001) and triglyceride (TG) levels (P = 0.001). There was no significant change in these parameters in the E-group. CONCLUSION: This prospective study shows that the treatment of postmenopausal women on oestrogen with low-dose oral methyltestosterone results in a significant reduction in plasma viscosity. This lowering of plasma viscosity was achieved despite an increase in fibrinogen levels. Significant lowering of lipoproteins, especially TG levels, might have been responsible for this benefit. The combination regimen did not result in major side-effects. Based on these results, we feel confident in recommending low-dose androgens to postmenopausal women with a history of sexual dysfunction and decreased libido.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Analysis_of_Variance_MeSH M_Blood_Viscosity_MeSH S_drug_effects_MeSH Blood_Viscosity_drug_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Fibrinogen_MeSH S_analysis_MeSH Fibrinogen_analysis_MeSH M_Human_MeSH M_Lipoproteins__HDL_MeSH S_blood_MeSH Lipoproteins__HDL_blood_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Medroxyprogesterone_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_therapeutic_use_MeSH M_Methyltestosterone_MeSH S_administration_&_dosage_MeSH Methyltestosterone_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Testosterone_Congeners_MeSH S_administration_&_dosage_MeSH Testosterone_Congeners_administration_&_dosage_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
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----K E
----T Cyclophosphamide, methotrexate and fluorouracil (CMF) versus hormonal ablation with leuprorelin acetate as adjuvant treatment of node-positive, premenopausal breast cancer patients: preliminary results of the TABLE-study (Takeda Adjuvant Breast cancer study with Leuprorelin Acetate).
----A PURPOSE: The objective of this study was to evaluate the efficacy and tolerability of leuprorelin acetate in adjuvant treatment in comparison to standard chemotherapy with CMF in premenopausal, estrogen-receptor-positive or unknown, node-positive patients with early breast cancer. PATIENTS AND METHODS: The patients were randomly assigned to receive either 2 years of hormone ablation with leuprorelin acetate 11.25 mg as a subcutaneous injection every three months or six courses of CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1 and 8, q 4 weeks). The primary study end-point was recurrence-free survival (RFS) after 2 years. Secondary end-points included overall survival, adverse events and hormonal suppression. RESULTS: Between 1995 and 1999, a total of 589 patients with breast cancer were randomized to treatment with leuprorelin acetate or CMF. The data of 227 patients were available for this first interim analysis. One hundred and ten and 117 patients were assigned to leuprorelin acetate and chemotherapy, respectively. Both treatment arms were well balanced for baseline characteristics. So far, no difference between the groups has emerged with respect to recurrence-free or overall survivaL Suppression of serum estradiol levels and menstruation was less marked in the CMF-group compared to the leuprorelin arm. The most common adverse events were low-grade hot flushes, weight gain and increased sweating in the leuprorelin-treated patients and alopecia, nausea and vomiting in the CMF-group. CONCLUSION: According to these preliminary results, ovarian suppression with leuprorelin acetate was as effective as standard chemotherapy for premenopausal women with hormone-sensitive, node-positive early breast cancer.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Antineoplastic_Combined_Chemotherapy_Protocols_MeSH S_administration_&_dosage_MeSH Antineoplastic_Combined_Chemotherapy_Protocols_administration_&_dosage_MeSH S_therapeutic_use_MeSH Antineoplastic_Combined_Chemotherapy_Protocols_therapeutic_use_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH S_pathology_MeSH Breast_Neoplasms_pathology_MeSH S_surgery_MeSH Breast_Neoplasms_surgery_MeSH M_Chemotherapy__Adjuvant_MeSH M_Comparative_Study_MeSH M_Cyclophosphamide_MeSH S_administration_&_dosage_MeSH Cyclophosphamide_administration_&_dosage_MeSH M_Disease-Free_Survival_MeSH M_Female_MeSH M_Fluorouracil_MeSH S_administration_&_dosage_MeSH Fluorouracil_administration_&_dosage_MeSH M_Human_MeSH M_Leuprolide_MeSH S_therapeutic_use_MeSH Leuprolide_therapeutic_use_MeSH M_Lymphatic_Metastasis_MeSH M_Methotrexate_MeSH S_administration_&_dosage_MeSH Methotrexate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Premenopause_MeSH M_Receptors__Estrogen_MeSH S_analysis_MeSH Receptors__Estrogen_analysis_MeSH M_Receptors__Progesterone_MeSH S_analysis_MeSH Receptors__Progesterone_analysis_MeSH M_Time_Factors_MeSH M_Treatment_Outcome_MeSH 
****** 12176121
----K E
----T Effects of estrogen on the vascular wall: vasomotor function and inflammation.
----A 
----P Journal_Article Review Review__Academic 
----M M_Acute-Phase_Reaction_MeSH M_Aged_MeSH M_Antilipemic_Agents_MeSH S_therapeutic_use_MeSH Antilipemic_Agents_therapeutic_use_MeSH M_Cardiovascular_Diseases_MeSH S_immunology_MeSH Cardiovascular_Diseases_immunology_MeSH S_physiopathology_MeSH Cardiovascular_Diseases_physiopathology_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Coronary_Disease_MeSH S_immunology_MeSH Coronary_Disease_immunology_MeSH S_physiopathology_MeSH Coronary_Disease_physiopathology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Cytokines_MeSH S_immunology_MeSH Cytokines_immunology_MeSH M_Endothelium__Vascular_MeSH S_immunology_MeSH Endothelium__Vascular_immunology_MeSH S_metabolism_MeSH Endothelium__Vascular_metabolism_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_physiology_MeSH Estrogens_physiology_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_metabolism_MeSH Lipoproteins__HDL_Cholesterol_metabolism_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_metabolism_MeSH Lipoproteins__LDL_Cholesterol_metabolism_MeSH M_Middle_Aged_MeSH M_Muscle__Smooth__Vascular_MeSH S_immunology_MeSH Muscle__Smooth__Vascular_immunology_MeSH S_metabolism_MeSH Muscle__Smooth__Vascular_metabolism_MeSH M_Patient_Selection_MeSH M_Postmenopause_MeSH S_metabolism_MeSH Postmenopause_metabolism_MeSH M_Randomized_Controlled_Trials_MeSH M_Vasodilation_MeSH S_physiology_MeSH Vasodilation_physiology_MeSH 
****** 12177098
----K E
----T Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.
----A PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P =.43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease > or = 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P =.26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.
----P Clinical_Trial Clinical_Trial__Phase_III Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_adverse_effects_MeSH Antineoplastic_Agents__Hormonal_adverse_effects_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH S_mortality_MeSH Breast_Neoplasms_mortality_MeSH S_pathology_MeSH Breast_Neoplasms_pathology_MeSH M_Comparative_Study_MeSH M_Disease-Free_Survival_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Antagonists_MeSH S_adverse_effects_MeSH Estrogen_Antagonists_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogen_Antagonists_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Neoplasm_Metastasis_MeSH M_Nitriles_MeSH S_adverse_effects_MeSH Nitriles_adverse_effects_MeSH S_therapeutic_use_MeSH Nitriles_therapeutic_use_MeSH M_North_America_MeSH S_epidemiology_MeSH North_America_epidemiology_MeSH M_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Survival_Rate_MeSH M_Triazoles_MeSH S_adverse_effects_MeSH Triazoles_adverse_effects_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12177099
----K E
----T Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.
----A PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.
----P Clinical_Trial Clinical_Trial__Phase_III Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_adverse_effects_MeSH Antineoplastic_Agents__Hormonal_adverse_effects_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH S_mortality_MeSH Breast_Neoplasms_mortality_MeSH S_pathology_MeSH Breast_Neoplasms_pathology_MeSH M_Comparative_Study_MeSH M_Disease-Free_Survival_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Antagonists_MeSH S_adverse_effects_MeSH Estrogen_Antagonists_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogen_Antagonists_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Logistic_Models_MeSH M_Middle_Aged_MeSH M_Neoplasm_Metastasis_MeSH M_Nitriles_MeSH S_adverse_effects_MeSH Nitriles_adverse_effects_MeSH S_therapeutic_use_MeSH Nitriles_therapeutic_use_MeSH M_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH M_Survival_Rate_MeSH M_Triazoles_MeSH S_adverse_effects_MeSH Triazoles_adverse_effects_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12190841
----K E
----T Intermittent progestin administration as part of hormone replacement therapy: long-term comparison between estradiol 1 mg combined with intermittent norgestimate and estradiol 2 mg combined with constant norethisterone acetate.
----A BACKGROUND: To decrease exposure to progestin during hormone replacement therapy (HRT), a novel oral regimen consisting of constant 17beta-estradiol (E2) daily plus intermittent norgestimate (NGM) has been developed. METHODS: A multicenter study compared the safety and efficacy of E2 1 mg daily plus intermittent NGM 90 micro g (3 days off, 3 days on) (n = 150) vs. a continuous oral dose of E2 2 mg plus norethisterone acetate (NETA) 1 mg (n = 172) daily, for a period of 2 years. Endometrial biopsies were performed at 1 and 2 years. Subjects recorded the occurrence of vasomotor symptoms, uterine bleeding, and adverse events on diary cards. RESULTS: At 2 years' follow-up, no subject had developed endometrial hyperplasia or cancer. Endometrial atrophy was seen in 75% of subjects using the intermittent NGM regimen and in 78% of women using the constant NETA regimen. Both groups maintained a 96% reduction in vasomotor symptoms up to 2 years. The rates of bleeding and/or spotting showed no difference between the groups, and at 2 years' follow-up, 73% of women in the intermittent NGM group and 83% of subjects in the constant NETA group were amenorrheic. There was a lower incidence of progestin-associated side-effects, such as abdominal discomfort, edema, painful bleeding episodes, and breast symptoms, with the intermittent progestin regimen vs. the constant progestin regimen. Intermittent NGM use was associated with an elevation in HDL- and HDL2-cholesterol, whereas constant NETA reduced these lipoproteins. CONCLUSIONS: The intermittent administration of a progestin, such as NGM, provides a new, well-tolerated regimen to achieve endometrial safety, an adequate rate of amenorrhea, and effective reduction of vasomotor symptoms in postmenopausal women.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article Multicenter_Study 
----M M_Adult_MeSH M_Aged_MeSH M_Biopsy_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Comparative_Study_MeSH M_Drug_Administration_Schedule_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH S_standards_MeSH Hormone_Replacement_Therapy_standards_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH M_Norgestrel_MeSH S_administration_&_dosage_MeSH Norgestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Norgestrel_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norgestrel_analogs_&_derivatives_MeSH M_Uterine_Hemorrhage_MeSH 
****** 12191852
----K E
----T Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial.
----A OBJECTIVES: To compare the effect of a soy rich diet and hormone replacement therapy (HRT) on the main biomarkers of bone turnover and bone mineral density (BMD) at postmenopausal age. METHODS: 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into a soy rich diet group, a HRT group, and a control group. Bone biomarkers and BMD were evaluated at baseline and after 6 months at the end of the study. RESULTS: Diet is not as effective as HRT in reducing the postmenopausal turnover; however diet stimulates bone osteoblastic activity, as evidenced by significant increase in osteocalcin concentrations. BMD decreases significantly only in the control group, but not in the intervention groups. CONCLUSIONS: Our data suggest that soy products could be effective in reducing the risk of osteoporosis in asymptomatic postmenopausal women, but our findings should be confirmed before recommending the diet as a valid alternative to HRT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Biological_Markers_MeSH S_analysis_MeSH Biological_Markers_analysis_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Collagen_MeSH S_analysis_MeSH Collagen_analysis_MeSH M_Comparative_Study_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Non-Steroidal_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Hydroxyproline_MeSH S_analysis_MeSH Hydroxyproline_analysis_MeSH M_Isoflavones_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteocalcin_MeSH S_analysis_MeSH Osteocalcin_analysis_MeSH M_Osteoporosis__Postmenopausal_MeSH S_diagnosis_MeSH Osteoporosis__Postmenopausal_diagnosis_MeSH S_diet_therapy_MeSH Osteoporosis__Postmenopausal_diet_therapy_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Peptides_MeSH S_analysis_MeSH Peptides_analysis_MeSH P_Phytotherapy_MeSH M_Plant_Preparations_MeSH P_Soybeans_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12196750
----K E
----T Efficacy of a low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for the treatment of moderate acne: A randomized, placebo-controlled trial.
----A BACKGROUND: Acne is a multifactorial disease in which androgens appear to play an important role. A low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel (EE/LNG) has been shown to improve biochemical markers of androgenicity. Lowering bioavailable androgens may improve acne. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a low-dose oral contraceptive containing 20 microg of EE and 100 microg of LNG for the treatment of moderate acne. METHODS: In a randomized, double-blind, placebo-controlled clinical trial, healthy female subjects (n = 371; >/=14 years old) with regular menstrual cycles and moderate facial acne were randomly assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts and clinician global assessment were performed at the end of each cycle. Patient self-assessments were collected and biochemical markers of androgenicity were also measured. RESULTS: At the end of the study, the number of inflammatory and total lesions was significantly lower with EE/LNG compared with placebo (P <.05). Patients in the EE/LNG group also had significantly better scores for clinician global and patient self-assessments than those in the placebo group (P <.05). Biochemical markers of androgenicity improved during EE/LNG treatment compared with placebo and baseline values. CONCLUSION: A low-dose oral contraceptive containing EE/LNG is effective and safe for the treatment of moderate acne.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Acne_Vulgaris_MeSH S_drug_therapy_MeSH Acne_Vulgaris_drug_therapy_MeSH M_Adolescent_MeSH M_Adult_MeSH M_Contraceptives__Oral__Synthetic_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Synthetic_administration_&_dosage_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Safety_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12197366
----K E
----T A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life.
----A OBJECTIVE: To compare continuous combined hormone replacement therapy (ccHRT) and raloxifene with respect to compliance and quality of life, which were predefined secondary endpoints of a large, prospective study designed to investigate the uterine effects of both treatments. DESIGN: Double-blind, randomised controlled trial of six-month duration. SETTING: One hundred and twenty-nine gynaecology hospital departments, clinics or practices specialised in women's healthcare, located in Europe, South Africa and Israel. POPULATION: Healthy postmenopausal women (n = 1008). MAIN OUTCOME MEASURES: Changes in quality of life using the Women's Health Questionnaire (WHQ) and compliance using a compliance questionnaire and pill count. Adverse event and early discontinuation rates and satisfaction with treatment using a visual analogue scale (VAS). RESULTS: Women taking raloxifene reported greater satisfaction with their treatment as assessed on the VAS (P = 0.004), and a lower proportion, as compared with ccHRT, reported being worried by the treatment (9.6% vs 20.2%, P < 0.01). Women taking ccHRT reported greater deterioration in scores from the WHQ for depressed mood and menstrual symptoms than those taking raloxifene (P < 0.01). For memory, vasomotor symptoms and sexual behaviour, the ccHRT group reported significantly greater mean improvements (P < 0.05). Over half (58.8%) of those taking raloxifene noticed no effect, 37.7% felt better and 3.4% felt worse as measured using the compliance questionnaire. Fifty percent of the women taking ccHRT felt better, 37.8% noticed no effect but over 10% felt worse. More women on raloxifene (94.6%) than on ccHRT (85.9%) reported that they were taking their double-blinded medication regularly (P < 0.01). CONCLUSIONS: A lower rate of adverse event-related discontinuations, the lack of negative effects on quality of life and a smaller proportion of women being worried by the drug treatment were associated with higher treatment satisfaction and better compliance in postmenopausal women taking ccHRT or raloxifene.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Breast_Diseases_MeSH S_chemically_induced_MeSH Breast_Diseases_chemically_induced_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Pain_MeSH S_chemically_induced_MeSH Pain_chemically_induced_MeSH M_Patient_Compliance_MeSH M_Patient_Satisfaction_MeSH M_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Raloxifene_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Selective_Estrogen_Receptor_Modulators_MeSH S_therapeutic_use_MeSH Selective_Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Refusal_MeSH M_Vasodilation_MeSH S_drug_effects_MeSH Vasodilation_drug_effects_MeSH 
****** 12208797
----K E
----T Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women.
----A BACKGROUND: The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2x2 retinoid-placebo trial. METHODS AND RESULTS: A total of 189 postmenopausal women were randomized to 50 microg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 microg/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI -9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI -14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was -48% (95% CI -85% to -7%, P=0.012), whereas fenretinide was associated with a mean change of -1% (95% CI -34% to 40%, P=0.79) compared with placebo. CONCLUSIONS: In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Antineoplastic_Agents_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents_therapeutic_use_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH M_Breast_Neoplasms_MeSH S_etiology_MeSH Breast_Neoplasms_etiology_MeSH S_prevention_&_control_MeSH Breast_Neoplasms_prevention_&_control_MeSH M_C-Reactive_Protein_MeSH S_analysis_MeSH C-Reactive_Protein_analysis_MeSH M_Comparative_Study_MeSH M_Coronary_Disease_MeSH S_etiology_MeSH Coronary_Disease_etiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Dermis_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Fenretinide_MeSH S_therapeutic_use_MeSH Fenretinide_therapeutic_use_MeSH M_Human_MeSH M_Kinetics_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12269863
----K E
----T Spotlight on rizatriptan in migraine.
----A Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated, and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2-4%). In conclusion, rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term, and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest that rizatriptan should be considered as a first-line treatment option in the management of migraine.
----P Journal_Article Review Review__Tutorial 
----M M_Animals_MeSH M_Human_MeSH M_Migraine_MeSH S_drug_therapy_MeSH Migraine_drug_therapy_MeSH M_Randomized_Controlled_Trials_MeSH M_Serotonin_Agonists_MeSH S_pharmacology_MeSH Serotonin_Agonists_pharmacology_MeSH S_therapeutic_use_MeSH Serotonin_Agonists_therapeutic_use_MeSH M_Treatment_Outcome_MeSH M_Triazoles_MeSH S_pharmacology_MeSH Triazoles_pharmacology_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12270857
----K E
----T Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance.
----A BACKGROUND: Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. METHODS AND RESULTS: Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01). CONCLUSIONS: Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article Validation_Studies 
----M M_Adult_MeSH M_Amenorrhea_MeSH S_chemically_induced_MeSH Amenorrhea_chemically_induced_MeSH S_complications_MeSH Amenorrhea_complications_MeSH M_Brachial_Artery_MeSH S_drug_effects_MeSH Brachial_Artery_drug_effects_MeSH S_physiopathology_MeSH Brachial_Artery_physiopathology_MeSH S_ultrasonography_MeSH Brachial_Artery_ultrasonography_MeSH M_Delayed-Action_Preparations_MeSH S_administration_&_dosage_MeSH Delayed-Action_Preparations_administration_&_dosage_MeSH S_adverse_effects_MeSH Delayed-Action_Preparations_adverse_effects_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH S_physiopathology_MeSH Endothelium__Vascular_physiopathology_MeSH S_ultrasonography_MeSH Endothelium__Vascular_ultrasonography_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Human_MeSH P_Magnetic_Resonance_Angiography_MeSH M_Male_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH M_Middle_Aged_MeSH M_Nitroglycerin_MeSH S_diagnostic_use_MeSH Nitroglycerin_diagnostic_use_MeSH M_Reference_Values_MeSH M_Reproducibility_of_Results_MeSH M_Support__Non-U_S__Gov't_MeSH M_Time_MeSH M_Ultrasonography__Interventional_MeSH M_Vascular_Diseases_MeSH S_chemically_induced_MeSH Vascular_Diseases_chemically_induced_MeSH S_complications_MeSH Vascular_Diseases_complications_MeSH S_physiopathology_MeSH Vascular_Diseases_physiopathology_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH S_physiopathology_MeSH Vasomotor_System_physiopathology_MeSH 
****** 12356628
----K E
----T Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
----A BACKGROUND: Postmenopausal estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL particles. Oral ERT-induced increases in plasma triglyceride, however, decrease LDL particle size, which may counteract this antioxidant effect. Because transdermal ERT decreases plasma triglyceride, it may not decrease LDL particle size and may preserve estrogen's antioxidant effect. The present study investigates whether transdermal ERT can eliminate the adverse effects of oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. METHODS AND RESULTS: Postmenopausal women received no treatment (n=12) or were treated with either 0.625 mg oral conjugated equine estrogen daily (n=16) or with transdermal estradiol (50 microg/d, n=16) for 3 months. Plasma lipids and the diameter of LDL particles were determined. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO4 and subsequent measurement of thiobarbituric acid reactive substance (TBARS) concentrations. Oral ERT significantly increased plasma triglyceride and decreased LDL diameter but did not affect LDL-derived TBARS concentrations. In contrast, transdermal ERT significantly decreased the concentrations of plasma triglyceride and LDL-derived TBARS and significantly increased LDL diameter. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r=-0.51, P<0.001) and LDL-derived TBARS (r=-0.50, P<0.001). CONCLUSIONS: Because transdermal, but not oral ERT, decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.
----P Journal_Article 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Body_Mass_Index_MeSH M_Copper_Sulfate_MeSH S_chemistry_MeSH Copper_Sulfate_chemistry_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Lipoproteins__LDL_MeSH S_blood_MeSH Lipoproteins__LDL_blood_MeSH S_chemistry_MeSH Lipoproteins__LDL_chemistry_MeSH M_Middle_Aged_MeSH M_Oxidation-Reduction_MeSH S_drug_effects_MeSH Oxidation-Reduction_drug_effects_MeSH M_Particle_Size_MeSH P_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Thiobarbituric_Acid_Reactive_Substances_MeSH S_chemistry_MeSH Thiobarbituric_Acid_Reactive_Substances_chemistry_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 12361820
----K E
----T Effects of hormone replacement therapy on C-reactive protein levels in healthy postmenopausal women: comparison between oral and transdermal administration of estrogen.
----A 
----P Journal_Article 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_C-Reactive_Protein_MeSH S_metabolism_MeSH C-Reactive_Protein_metabolism_MeSH M_Cardiovascular_Diseases_MeSH S_blood_MeSH Cardiovascular_Diseases_blood_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Case-Control_Studies_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Women's_Health_MeSH 
****** 12364420
----K E
----T Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women.
----A Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF kappa B ligand. OPG has been shown to be an important inhibitor of osteoclast differentiation and activation in rodent models. Estrogen is known to suppress bone resorption, and the action of estrogen on bone may be mediated by OPG. The relationship between endogenous estrogen and circulating OPG levels and bone status in human populations is unclear. Thus, the aim of this study was to investigate the relationship between biochemical markers of bone turnover and bone density and circulating OPG and endogenous estradiol levels in a population-based cohort of postmenopausal women. Subjects were 180 women ages 55-91 yr (mean age, 67 yr). Serum estradiol was measured using an auto-analyzer. Serum concentrations of OPG were determined by ELISA. Markers of bone formation and resorption were measured by standard methods. Bone mineral density at total body, total hip, femoral neck, and lumbar spine was measured by dual energy x-ray absorptiometry. There was a significant inverse relationship between estradiol and all bone turnover markers (r-values from -0.46 to -0.23; P < 0.05). Serum estradiol was positively related to absolute bone density at all sites and to change in bone density at the hip and femoral neck by univariate analysis (r-values from 0.15-0.29; P < 0.05). We observed a weak inverse association between OPG and serum-based bone turnover markers (r-values -0.18 and -0.16; P < 0.05). There was a significant positive relationship between OPG and bone mineral density at total body, total hip, and femoral neck (r-values from 0.17-0.2; P < 0.05) by univariate analysis, which was lost after adjustment for age and body mass index. There was a significant weak positive relationship between circulating OPG and serum estradiol (r = 0.18; P < 0.02). We observed no significant relationships between OPG and bone turnover markers measured in urine. We conclude that the variation in circulating endogenous estradiol levels is an important factor contributing to levels of bone turnover and bone density at the menopause. Our observations also suggest that circulating levels of OPG may reflect OPG activity in bone and are related to circulating endogenous levels of estradiol. We have previously reported high levels of variability in urine markers of bone resorption, and we suggest that this could account for the absence of a significant association between these markers and circulating OPG.
----P Journal_Article 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Analysis_of_Variance_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH M_Body_Mass_Index_MeSH P_Bone_Density_MeSH P_Bone_Remodeling_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Femur_MeSH M_Glycoproteins_MeSH S_blood_MeSH Glycoproteins_blood_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_Receptors__Cytoplasmic_and_Nuclear_MeSH S_blood_MeSH Receptors__Cytoplasmic_and_Nuclear_blood_MeSH M_Regression_Analysis_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12370107
----K E
----T Comparison of high-dose finasteride (5 mg/day) versus low-dose finasteride (2.5 mg/day) in the treatment of hirsutism.
----A OBJECTIVE: To compare the clinical efficacy and safety of high-dose (5 mg/day) and low-dose (2.5 mg/day) finasteride in the treatment of hirsutism in women. DESIGN: A prospective, randomized and controlled clinical trial. METHODS: Fifty-six hirsute women with moderate to severe hirsutism were prospectively evaluated to see the effects of low-dose (2.5 mg/day) and high-dose (5 mg/day) finasteride. Patients were randomly divided into two treatment groups. Group I (n=29) received 2.5 mg finasteride/day and group II (n=27) received 5 mg finasteride/day orally for 1 year. Hirsutism score, body mass index and hormonal parameters (FSH, LH, estradiol, androstenedione, testosterone, free testosterone, 17alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate and sex hormone-binding globulin) were measured in all the patients before treatment and repeated at six-monthly intervals. RESULTS: The hirsutism scores decreased significantly at months 6 and 12 from a mean+/-s.d. of 18.4+/-4.6 to 13.3+/-5.2 (P<0.001) and 18.4+/-4.6 to 8.6+/-4.2 (P<0.001) in group I and from 18.7+/-5.2 to 13.9+/-5.3 (P<0.001) and 18.7+/-5.2 to 10.3+/-5.0 (P<0.001) in group II respectively. No significant changes in the blood chemistry and hormonal parameters except estradiol levels were observed. No serious side-effects were seen in the two groups. In group II, estradiol levels increased significantly at 6 and 12 months. CONCLUSIONS: In this study, hirsutism scores decreased significantly at 6 and 12 months in both groups I and II. Low-dose (2.5 mg/day) finasteride is safe and cost effective in the treatment of hirsutism and may be used instead of high-dose finasteride (5 mg/day) therapy.
----P Clinical_Trial Randomized_Controlled_Trial 
----M M_17-alpha-Hydroxyprogesterone_MeSH S_blood_MeSH 17-alpha-Hydroxyprogesterone_blood_MeSH M_Adolescent_MeSH M_Adult_MeSH M_Androstenedione_MeSH S_blood_MeSH Androstenedione_blood_MeSH M_Comparative_Study_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_blood_MeSH Dehydroepiandrosterone_Sulfate_blood_MeSH M_Enzyme_Inhibitors_MeSH S_administration_&_dosage_MeSH Enzyme_Inhibitors_administration_&_dosage_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Finasteride_MeSH S_administration_&_dosage_MeSH Finasteride_administration_&_dosage_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hirsutism_MeSH S_blood_MeSH Hirsutism_blood_MeSH S_drug_therapy_MeSH Hirsutism_drug_therapy_MeSH M_Human_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_metabolism_MeSH Sex_Hormone-Binding_Globulin_metabolism_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12382352
----K E
----T Hormone replacement therapy--a dilemma.
----A 
----P Editorial 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_chemically_induced_MeSH Breast_Neoplasms_chemically_induced_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH M_Cardiovascular_Diseases_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH P_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Assessment_MeSH M_Risk_Factors_MeSH 
****** 12390622
----K E
----T Hormone supplementation differently affects migraine in postmenopausal women.
----A OBJECTIVE: To evaluate the effects of three schemes of oral hormone replacement therapy (HRT) on migraine course in postmenopausal women. METHODS: Thirty-eight patients presenting for clinical evaluation of menopausal status and suffering from migraine were enrolled. The observational period lasted 7 months, during which women filled in a daily diary with the clinical features of headache attacks and analgesic use. We evaluated climacteric symptoms, anxiety and depression. After a 1-month run-in period, women were assigned to one of three regimens of HRT: estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day for 28 days, in a continuous combined scheme; oral conjugated estrogens 0.625 mg/day for 28 days plus medroxyprogesterone acetate 10 mg/day in the last 14 days, in a sequential continuous scheme; and estradiol valerate 2 mg/day for 21 days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical scheme. Follow-up evaluations were performed at 3 and 6 months. RESULTS: During the run-in period, the three subgroups of patients were similar as far as the features of migraine are concerned. Overall, a progressive increase in attack frequency (from 2.2 +/- 1.0 to 3.8 +/- 1.3, P<.001), days with headache (from 3.4 +/- 1.3 to 4.9 +/- 1.9, P<.001), and analgesic consumption (from 3.4 +/- 1.3 to 5.6 +/- 2.2, P<.001) was observed after 6 months. Duration of attacks decreased (from 18.1 +/- 7.4 to 13.6 +/- 4.2 hours, P =.005), whereas severity worsened (from 1.9 +/- 0.2 to 2.1 +/- 0.2, P<.001). The increase in number of days with headache and number of analgesics used was smaller in the group receiving the continuous combined regimen than in the other two groups. CONCLUSION: Although HRT typically will lead to some worsening of headache syndrome, estradiol hemihydrate plus norethisterone given in a combined continuous scheme was the regimen best tolerated by our patients.
----P Journal_Article 
----M M_Estrogens_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Migraine_MeSH S_chemically_induced_MeSH Migraine_chemically_induced_MeSH P_Postmenopause_MeSH M_Progestins_MeSH S_adverse_effects_MeSH Progestins_adverse_effects_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12401147
----K E
----T Do the risks of estrogen plus progestin outweigh the benefits in healthy post-menopausal women?
----A 
----P Journal_Article 
----M 
****** 12407324
----K E
----T [Postmenopausal hormonal treatment: conventional hormone replacement therapy or tibolone? Effects on bone]
----A OBJECTIVE: Our purpose was to review with critical analysis, data from randomized controlled clinical trials comparing the effects on bone of conventional hormone replacement therapy (HRT) and tibolone. Their respective effects on bone were also reviewed and summarized. Materials and methods. Medline via PubMed was searched using a combination of the following key words "tibolone, estrogens and bone" to identify all randomized controlled trials tibolone versus HRT (1960-2001). RESULTS: Six randomized controlled trials that have been carried out to compare effects of tibolone and conventional HRT on prevention of postmenopausal bone loss were identified. Only one of these trials has been performed with a correct methodology (double-blind and with an adequate duration). In this trial over 2 years, the highest significant increase from baseline in bone mineral density (BMD) at all sites was observed with HRT; in addition, HRT showed a significantly greater increase in BMD at lumbar spine than tibolone. Randomized placebo-controlled trials have demonstrated that tibolone produces positive effects on BMD. Nevertheless, no clinical convincing data are available to support its efficacy in the prevention of osteoporotic fractures. The positive impact on BMD of conventional HRT to prevent postmenopausal bone loss and to treat established osteoporosis has been shown by many randomized controlled trials. Regarding fracture risk prevention, some clinical and epidemiological data suggest that HRT initiated in early or late postmenopause may prevent fractures if it is administered at standard doses and continued for a long time. CONCLUSION: HRT is always the reference treatment of postmenopausal symptoms related to estrogen deficiency.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH M_English_Abstract_MeSH M_Estrogen_Receptor_Modulators_MeSH S_pharmacology_MeSH Estrogen_Receptor_Modulators_pharmacology_MeSH S_therapeutic_use_MeSH Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Fractures_MeSH S_etiology_MeSH Fractures_etiology_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_pharmacology_MeSH Norpregnenes_pharmacology_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_complications_MeSH Osteoporosis__Postmenopausal_complications_MeSH S_pathology_MeSH Osteoporosis__Postmenopausal_pathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH P_Patient_Selection_MeSH M_Randomized_Controlled_Trials_MeSH S_standards_MeSH Randomized_Controlled_Trials_standards_MeSH M_Research_Design_MeSH S_standards_MeSH Research_Design_standards_MeSH M_Time_Factors_MeSH M_Treatment_Outcome_MeSH 
****** 12414849
----K E
----T The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer.
----A To examine the effect of estradiol (E(2)) without the confounding effect of hypothalamic-pituitary feedback, we studied men with prostate cancer in whom gonadotropin secretion was suppressed by LH-releasing hormone agonists (LHRH-A). Fourteen men over 65 yr of age and receiving established LHRH-A treatment (EST group) without bony metastases and 12 men who received LHRH-A as neoadjuvant therapy for locally advanced prostate cancer (NEO group) were randomized (double blind) to receive either 1 mg/d micronized E(2) (n = 12) or placebo (PL; n = 13) for 9 wk. E(2), estrone, testosterone, SHBG, PTH, and 25-hydroxy- and 1,25-dihydroxyvitamin D levels as well as markers of bone resorption [N- and C-telopeptide cross-links (NTX and CTX) and deoxypyridinoline] and bone formation (bone-specific alkaline phosphatase, osteocalcin, and N-terminal type I collagen) were measured before LHRH-A in the NEO group, before [baseline (BL)] and after 9 wk of E(2) or PL in all patients, and 6 wk after E(2) treatment in the EST group. In the NEO group, hormone levels fell 3 wk after the initial LHRH-A injection, and deoxypyridinoline increased significantly (P = 0.006). At BL, the EST group had higher bone turnover due to the longer duration of LHRH-A treatment. With E(2) treatment, E(2) levels rose into the normal male range, and two resorption markers decreased significantly from BL by 33% for NTX (P < 0.001) and 28% for CTX (P = 0.009). Bone formation markers did not change. PTH increased by 43% from BL (P < 0.01) in the E(2) group and decreased 16% from BL in the PL group (P < 0.01). Ionized calcium did not change in the E(2) group, but increased in the PL group by 2.3% (P < 0.01). NTX and CTX increased 6 wk after E(2) withdrawal in the EST group. We conclude that E(2) inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Amino_Acids_MeSH S_urine_MeSH Amino_Acids_urine_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Calcifediol_MeSH S_blood_MeSH Calcifediol_blood_MeSH M_Calcitriol_MeSH S_blood_MeSH Calcitriol_blood_MeSH M_Calcium_MeSH S_blood_MeSH Calcium_blood_MeSH S_urine_MeSH Calcium_urine_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Gonadorelin_MeSH S_analogs_&_derivatives_MeSH Gonadorelin_analogs_&_derivatives_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Parathyroid_Hormone_MeSH S_blood_MeSH Parathyroid_Hormone_blood_MeSH M_Peptide_Fragments_MeSH S_blood_MeSH Peptide_Fragments_blood_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Placebos_MeSH M_Procollagen_MeSH S_blood_MeSH Procollagen_blood_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12414850
----K E
----T Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers.
----A In a 5-yr randomized prospective study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy (ERT/HRT), calcitriol, ERT/HRT and calcitriol, or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density (BMD), calciotropic hormones, markers of bone remodeling, and calcium absorption in 489 elderly women. The treatment phase of the study was double-blinded. After discontinuing therapy for 2 yr, there was rapid bone loss in all 3 treatment groups, and most of the decrease in BMD occurred in the first year. In the ERT/HRT group, spine BMD increased 5.5% in yr 3, decreased 3.2% in yr 4, and decreased 0.7% in yr 5; femoral neck BMD increased 3.7% in yr 3, decreased 2.5% in yr 4, and decreased 0.4% in yr 5; total body BMD increased 2.1% in yr 3, decreased 1.4% in yr 4, and decreased 0.6% in yr 5. In the combination group, spine BMD increased 7.1% in yr 3, decreased 4.3% in yr 4, and decreased 0.3% in yr 5; femoral neck BMD increased 4.5% in yr 3, decreased 3.0% in yr 4, and decreased 0.01% in yr 5; total body BMD increased 2.2% in yr 3, decreased 1.5% in yr 4, and decreased 0.6% in yr 5. In the calcitriol group, spine BMD increased 1.8% in yr 3, decreased 1.8% in yr 4, and showed no change in yr 5; femoral neck BMD increased 0.2% in yr 3, decreased 0.2% in yr 4, and decreased 0.6% in yr 5; total body BMD decreased 0.4% in yr 3, decreased 0.6% in yr 4, and decreased 0.4% in yr 5. Compared with placebo, all treated groups at yr 5 had significantly higher total body BMD; only the combination group had significantly higher spine BMD (3.4%; P < 0.001) and total hip BMD (2.4%; P < 0.01.) compared with the placebo group. Compared with baseline, only spine BMD in the combination group was significantly higher (2.6%; P < 0.001) at yr 5. The increase in calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment, and the decrease in bone markers was reversed in the hormone-treated groups. These results suggest that discontinuation of ERT/HRT and/or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment; however, in the combination group there was a statistically significant residual effect on spine BMD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Absorption_MeSH M_Aged_MeSH M_Biological_Markers_MeSH S_analysis_MeSH Biological_Markers_analysis_MeSH P_Bone_Density_MeSH M_Bone_Remodeling_MeSH M_Calcifediol_MeSH S_blood_MeSH Calcifediol_blood_MeSH M_Calcitriol_MeSH S_administration_&_dosage_MeSH Calcitriol_administration_&_dosage_MeSH M_Calcium_MeSH S_metabolism_MeSH Calcium_metabolism_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Femur_MeSH M_Human_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Parathyroid_Hormone_MeSH S_blood_MeSH Parathyroid_Hormone_blood_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Placebos_MeSH M_Prospective_Studies_MeSH M_Questionnaires_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12414853
----K E
----T Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial.
----A Young women with anorexia nervosa (AN) have subnormal levels of dehydroepiandrosterone (DHEA) and estrogen that may be mechanistically linked to the bone loss seen in this disease. The purpose of this study was to compare the effects of a 1-yr course of oral DHEA treatment vs. conventional hormonal replacement therapy (HRT) in young women with AN. Sixty-one young women were randomly assigned to receive oral DHEA (50 mg/d) or HRT (20 micro g ethinyl estradiol/0.1 mg levonorgestrel). Anthropometric, nutrition, and exercise data were acquired every 3 months, and bone mineral density (BMD) and body composition were measured by dual energy x-ray absorptiometry (DXA) every 6 months over 1 yr. Serum samples were obtained for measurements of hormones, proresorptive cytokines, and bone formation markers, and urine was collected for determinations of bone resorption markers at each visit. In initial analyses, total hip BMD increased significantly and similarly (+1.7%) in both groups. Hip BMD increases were positively correlated with increases in IGF-I (r = 0.44; P = 0.030) and the bone formation marker, bone-specific alkaline phosphatase increased significantly only in the DHEA treatment group (P = 0.003). However, both groups gained significant amounts of weight over the year of therapy, and after controlling for weight gain, no treatment effect was detectable. There was no significant change in lumbar BMD in either group. Both bone formation markers, bone-specific alkaline phosphatase and osteocalcin, increased transiently at 6-9 months in those subjects receiving DHEA compared with the estrogen-treated group (P < 0.05). Both DHEA and HRT significantly reduced levels of the bone resorption markers, urinary N-telopeptides (P < 0.05). There was a positive correlation between changes in IGF-I and changes in weight, body fat determined by DXA, and estradiol for both groups. In addition, patients receiving DHEA exhibited improvement on three validated psychological instruments (Eating Attitudes Test, Anorexia Nervosa Subtest, and Spielberger Anxiety Inventory). Both DHEA and HRT had similar effects on hip and spinal BMD. Over the year of treatment, maintenance of both hip and spinal BMD was seen, but there was no significant increase after accounting for weight gain. Compared with HRT, DHEA appeared to have anabolic effects, evidenced by the positive correlation between increases in hip DXA measurements and IGF-I and significant increases in bone formation markers. Both therapies significantly decreased bone resorption. Replicating results from studies of the elderly, DHEA resulted in improvements in specific psychological parameters in these young women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adipose_Tissue_MeSH M_Adolescent_MeSH M_Adult_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Anorexia_Nervosa_MeSH S_complications_MeSH Anorexia_Nervosa_complications_MeSH S_drug_therapy_MeSH Anorexia_Nervosa_drug_therapy_MeSH S_psychology_MeSH Anorexia_Nervosa_psychology_MeSH M_Body_Composition_MeSH M_Body_Image_MeSH M_Body_Weight_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Collagen_MeSH S_urine_MeSH Collagen_urine_MeSH M_Dehydroepiandrosterone_MeSH S_therapeutic_use_MeSH Dehydroepiandrosterone_therapeutic_use_MeSH M_Energy_Intake_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH M_Menstrual_Cycle_MeSH M_Nutrition_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Osteoporosis_MeSH S_etiology_MeSH Osteoporosis_etiology_MeSH S_prevention_&_control_MeSH Osteoporosis_prevention_&_control_MeSH M_Peptides_MeSH S_urine_MeSH Peptides_urine_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12435217
----K E
----T Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials.
----A BACKGROUND: Women commonly use soy products, herbs, and other complementary and alternative medicine (CAM) therapies for menopausal symptoms. Randomized, controlled trials have evaluated the efficacy and short-term safety of these therapies. PURPOSE: To review randomized, controlled trials of CAM therapies for menopausal symptoms in order to better inform practice and guide future research. DATA SOURCES: Searches of MEDLINE for articles published from January 1966 through March 2002, of the Alternative and Complementary Database (AMED) of the British Library for articles published from January 1985 through December 2000, and of the authors' own extensive files. Search terms were hot flash/flush, menopause, and climacteric, combined with phytoestrogens, alternative medicine, herbal medicine, traditional medicine, Traditional Chinese Medicine (TCM ), Ayurveda, naturopathy, chiropractic, osteopathy, massage, yoga, relaxation therapy, homeopathy, aromatherapy, and therapeutic touch. STUDY SELECTION: 29 randomized, controlled clinical trials of CAM therapies for hot flashes and other menopausal symptoms were identified; of these, 12 dealt with soy or soy extracts, 10 with herbs, and 7 with other CAM therapies. DATA EXTRACTION: Each author extracted information from half of the studies on the number of patients, study design, outcome measures, and results; the other author then checked these results. DATA SYNTHESIS: Soy seems to have modest benefit for hot flashes, but studies are not conclusive. Isoflavone preparations seem to be less effective than soy foods. Black cohosh may be effective for menopausal symptoms, especially hot flashes, but the lack of adequate long-term safety data (mainly on estrogenic stimulation of the breast or endometrium) precludes recommending long-term use. Single clinical trials have found that dong quai, evening primrose oil, a Chinese herb mixture, vitamin E, and acupuncture do not affect hot flashes; two trials have shown that red clover has no benefit for treating hot flashes. CONCLUSIONS: Black cohosh and foods that contain phytoestrogens show promise for the treatment of menopausal symptoms. Clinical trials do not support the use of other herbs or CAM therapies. Long-term safety data on individual isoflavones or isoflavone concentrates are not available.
----P Journal_Article Review Review__Academic 
----M M_Acupuncture_MeSH M_Behavior_Therapy_MeSH P_Complementary_Therapies_MeSH M_Diet_MeSH M_Estrogens__Non-Steroidal_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Hot_Flashes_MeSH S_therapy_MeSH Hot_Flashes_therapy_MeSH M_Human_MeSH M_Isoflavones_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Ointments_MeSH M_Plant_Preparations_MeSH S_therapeutic_use_MeSH Plant_Preparations_therapeutic_use_MeSH M_Progesterone_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Randomized_Controlled_Trials_MeSH M_Soybean_Proteins_MeSH S_therapeutic_use_MeSH Soybean_Proteins_therapeutic_use_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Vitamin_E_MeSH S_therapeutic_use_MeSH Vitamin_E_therapeutic_use_MeSH 
****** 12440549
----K E
----T Hot flashes: the old and the new, what is really true?
----A OBJECTIVE: To obtain pilot prospective data regarding the efficacy and tolerability of gabapentin for alleviating hot flashes. PATIENTS AND METHODS: This prospective single-arm clinical trial was conducted between July 26, 2001, and November 30, 2001. Patients underwent a baseline week and then 4 weeks of gabapentin treatment, with increasing doses during the first 3 weeks, from 300 to 600 to 900 mg/d. Data were obtained primarily from patient-completed questionnaires. RESULTS: Data from 20 evaluable women (of 24 entered in the trial) were available. Four patients discontinued use of gabapentin for perceived drug-related untoward symptoms, primarily related to light-headedness and dizziness. The 16 patients who completed this clinical trial had a mean reduction in hot flash frequency, in the fourth treatment week compared to the baseline week, of 66%. Their corresponding hot flash score (frequency times average severity) reduction was 70%. Additionally, patients who completed the 4 treatment weeks had a strong tendency to report an improvement in several other symptoms. CONCLUSION: Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with hot flashes, the available data suggest that gabapentin is a reasonable treatment to consider in patients with hot flashes if they do not wish to use hormonal therapy.
----P Comment Editorial 
----M M_Aged_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH S_metabolism_MeSH Estradiol_metabolism_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_epidemiology_MeSH Hot_Flashes_epidemiology_MeSH S_etiology_MeSH Hot_Flashes_etiology_MeSH M_Human_MeSH M_Incidence_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Prognosis_MeSH M_Risk_Assessment_MeSH 
****** 12440557
----K E
----T Pathophysiology and treatment of hot flashes.
----A Hot flashes affect about three fourths of postmenopausal women and are one of the most common health problems in this demographic group. Dysfunction of central thermoregulatory centers caused by changes in estrogen levels at the time of menopause has long been postulated to be the cause of hot flashes. Treatment should begin with a careful patient history, with specific attention to the frequency and severity of hot flashes and their effect on the individual's function. For mild symptoms that do not interfere with sleep or daily function, behavioral changes in conjunction with vitamin E (800 IU/d) use is a reasonable initial approach. For more severe symptoms, the next step is to determine whether there is a contraindication or a personal reservation to estrogen replacement therapy. For women who are able and willing to use estrogen, it will successfully relieve symptoms by about 80% to 90%. In patients with a history of breast or uterine cancer, treatment with the progestational agent megesterol acetate appears to be a safe alternative that also decreases hot flashes by approximately 80%. For women unwilling or unable to use hormone therapy, one of the newer antidepressant agents can be prescribed. Venlafaxine decreases hot flashes by about 60%. Gabapentin is another drug that appears promising as therapy for women unable or unwilling to use estrogen, and the results of ongoing trials to determine its efficacy are eagerly awaited. The use of clonidine, methyldopa, and belladonna should be discouraged because of their modest efficacy and adverse effects.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Antidepressive_Agents_MeSH S_therapeutic_use_MeSH Antidepressive_Agents_therapeutic_use_MeSH M_Combined_Modality_Therapy_MeSH M_Drug_Therapy__Combination_MeSH P_Exercise_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_standards_MeSH Hormone_Replacement_Therapy_standards_MeSH S_trends_MeSH Hormone_Replacement_Therapy_trends_MeSH M_Hot_Flashes_MeSH S_diagnosis_MeSH Hot_Flashes_diagnosis_MeSH S_therapy_MeSH Hot_Flashes_therapy_MeSH M_Human_MeSH M_Life_Style_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Prognosis_MeSH P_Relaxation_Techniques_MeSH M_Sensitivity_and_Specificity_MeSH M_Severity_of_Illness_Index_MeSH M_Treatment_Outcome_MeSH 
****** 12459399
----K E
----T Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study.
----A PURPOSE: To determine if hormone therapy results in better cognitive function in older postmenopausal women. SUBJECTS AND METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized, placebo-controlled trial involving 2763 women with coronary disease. Women were assigned randomly to conjugated estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) in one tablet daily or identical placebo; they were followed for a mean (+/- SD) of 4.2 +/- 0.4 years. Participants at 10 of the 20 HERS centers were invited to enroll in the cognitive function substudy. At the end of the trial, we measured cognitive function in 517 women in the hormone group and 546 in the placebo group using six standard tests: the modified Mini-Mental Status Examination, Verbal Fluency, Boston Naming, Word List Memory, Word List Recall, and Trails B. Cognitive function was not measured at baseline. RESULTS: The mean age of participants at the time of cognitive function testing was 71 +/- 6 years. There were no differences in age-adjusted cognitive function test scores between the two treatment groups, except that women assigned to hormones scored worse on the Verbal Fluency test than women assigned to placebo (15.9 +/- 4.8 vs. 16.6 +/- 4.8, P = 0.02). Adjustment for other potential confounders and restriction of the analyses to women who had been adherent to study medication did not change the results. CONCLUSION: Among older postmenopausal women with coronary disease, 4 years of treatment with postmenopausal hormone therapy did not result in better cognitive function as measured on six standardized tests. Whether these results also apply to elderly women without coronary disease cannot be determined from this study.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Cognition_Disorders_MeSH S_prevention_&_control_MeSH Cognition_Disorders_prevention_&_control_MeSH M_Coronary_Disease_MeSH S_drug_therapy_MeSH Coronary_Disease_drug_therapy_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Combinations_MeSH P_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_Treatment_Outcome_MeSH 
****** 12459411
----K E
----T Cognitive effects of estrogens in women with cardiac disease: what we do not know.
----A 
----P Comment Editorial 
----M M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Cognition_Disorders_MeSH S_prevention_&_control_MeSH Cognition_Disorders_prevention_&_control_MeSH M_Coronary_Disease_MeSH S_drug_therapy_MeSH Coronary_Disease_drug_therapy_MeSH M_Drug_Combinations_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Randomized_Controlled_Trials_MeSH M_Research_Design_MeSH 
****** 12458987
----K E
----T Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial.
----A BACKGROUND: Combination therapy with alendronate and estrogen for 2 years increases bone mineral density at the spine and hip more than does therapy with either agent alone. Changes in bone mineral density after discontinuation of therapy have not been compared directly. OBJECTIVE: To determine the rate of bone loss when therapy with alendronate, estrogen, or both agents is discontinued. DESIGN: Double-blind, placebo-controlled discontinuation trial. SETTING: 18 U.S. centers. PATIENTS: 244 postmenopausal, hysterectomized women 44 to 77 years of age. INTERVENTION: 2 years of therapy with alendronate, 10 mg/d (n = 92); conjugated estrogen, 0.625 mg/d (n = 143); alendronate and conjugated estrogen (n = 140); or placebo (n = 50). At year 3, women were allocated into five groups: Twenty-eight women continued to take placebo and 44 women continued to take combination therapy, but 50 women taking alendronate, 81 taking conjugated estrogen, and 41 taking combination therapy were switched to placebo. MEASUREMENTS: Bone mineral density and biochemical markers of bone turnover. RESULTS: Women taking alendronate or combination therapy who were switched to placebo for year 3 of the study maintained bone mass. Bone mineral density in these women was 4.1% (CI, 2.6% to 5.7%) and 6.6% (CI, 5.0% to 8.2%) higher, respectively, at the spine (P < 0.001 for both treatment comparisons) and 3.5% (CI, 2.3% to 4.6%) and 3.0% (CI, 1.8% to 4.2%) higher, respectively, at the trochanter (P < 0.001 for both treatment comparisons) than that in women previously taking estrogen who were switched to placebo. In contrast, women who were taking estrogen and were switched to placebo during year 3 experienced a 4.5% decrease at the spine (95% CI, -5.0% to -4.0%) and a 2.4% decrease at the trochanter (CI, -2.7% to -2.1%) (P < 0.001 for both changes). Compared with women who took placebo for 3 years, women who took estrogen for 2 years and were then switched to placebo had a bone mineral density that was 2.9% higher (CI, 1.2% to 4.6%) at the spine (P < 0.05) and 2.9% higher (CI, 1.6% to 4.2%) at the trochanter (P < 0.001). Changes in biochemical markers during year 3 did not differ among the groups that discontinued active treatment. CONCLUSIONS: Accelerated bone loss is seen after withdrawal of estrogen therapy but not after withdrawal of alendronate or combination therapy. The differential effects after withdrawal of therapy should be considered in the management of postmenopausal osteoporosis.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alendronate_MeSH S_adverse_effects_MeSH Alendronate_adverse_effects_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Biological_Markers_MeSH S_analysis_MeSH Biological_Markers_analysis_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Hip_MeSH S_physiology_MeSH Hip_physiology_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_Withholding_Treatment_MeSH 
****** 12490680
----K E
----T Herbal medicines--what's in the bottle?
----A 
----P Comment Journal_Article 
----M P_Complementary_Therapies_MeSH M_Drug_Contamination_MeSH M_Drug_Labeling_MeSH M_Human_MeSH P_Medicine__Herbal_MeSH M_Phytotherapy_MeSH S_adverse_effects_MeSH Phytotherapy_adverse_effects_MeSH 
****** 7807658
----K E
----T Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.
----A OBJECTIVE--To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women. DESIGN--A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. PARTICIPANTS--A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. INTERVENTION--Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. PRIMARY ENDPOINTS--Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. ANALYSIS--Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. RESULTS--Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. CONCLUSIONS--Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Endometrial_Hyperplasia_MeSH S_chemically_induced_MeSH Endometrial_Hyperplasia_chemically_induced_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Fibrinogen_MeSH S_drug_effects_MeSH Fibrinogen_drug_effects_MeSH S_metabolism_MeSH Fibrinogen_metabolism_MeSH M_Glucose_MeSH S_metabolism_MeSH Glucose_metabolism_MeSH M_Heart_Diseases_MeSH S_epidemiology_MeSH Heart_Diseases_epidemiology_MeSH S_prevention_&_control_MeSH Heart_Diseases_prevention_&_control_MeSH M_Human_MeSH M_Insulin_MeSH S_blood_MeSH Insulin_blood_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH S_drug_effects_MeSH Lipoproteins__HDL_Cholesterol_drug_effects_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Risk_Factors_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Systole_MeSH S_drug_effects_MeSH Systole_drug_effects_MeSH M_Weight_Gain_MeSH 
****** 7824251
----K I
----T Hormone replacement therapy and endometrial cancer risk: a meta-analysis.
----A OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. DATA SOURCES: A literature search of English-language studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF STUDY SELECTION: We identified 30 studies with adequate controls and risk estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two authors and summarized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of unopposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for endometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial cancer risk increases substantially with long duration of unopposed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically significant, the risk of death from endometrial cancer among unopposed estrogen users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen plus progestin users are limited and conflicting.
----P Journal_Article Meta-Analysis 
----M M_Endometrial_Neoplasms_MeSH S_chemically_induced_MeSH Endometrial_Neoplasms_chemically_induced_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Postmenopause_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH S_adverse_effects_MeSH Progestins_adverse_effects_MeSH M_Risk_Factors_MeSH 
****** 7778430
----K I
----T A quality of life perspective on who benefits from estradiol replacement therapy.
----A STUDY OBJECTIVE. To examine who may benefit from estrogen replacement therapy from a quality of life (QoL) perspective, taking both disease-specific and general aspects at baseline into account. DESIGN. A double-blind multi-center randomized placebo-controlled prospective study. The subjects were randomized to receive either transdermal estradiol or placebo for 12 weeks. QoL measures were disease-specific and generic. LOCATION. University hospital, teaching hospital and private practice. MATERIAL. Post-menopausal volunteering Swedish women (n = 223) with mild to severe climacteric symptoms, as clinically evaluated by the Kupperman's Index. RESULTS. All QoL assessments showed highly significant improvement in the estradiol group in comparison with the placebo group. The women receiving placebo treatment also improved, but their improvement reached a peak at six weeks of treatment and then declined. In the estradiol group the improvement continued throughout the 12 weeks. After 12 weeks of treatment the change in the placebo-treated group was smaller on the disease-specific scales than on the generic scales and the Kupperman's Index. A high correlation was seen between the baseline score for a certain QoL assessment and the change in this score during treatment. The most striking result was that the mean change in QoL for the two groups was statistically significant for almost any pre-treatment QoL status. CONCLUSIONS. Women with slightly, moderately or severely diminished QoL status would benefit from estrogen treatment during the climacteric period. A similar tendency was seen in women with mild symptoms at baseline.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH P_Quality_of_Life_MeSH M_Sweden_MeSH 
****** 7598140
----K I
----T Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four-year randomized study.
----A BACKGROUND: Administration of estrogen or etidronate has been shown to increase bone mineral density in postmenopausal women. This 4-year, prospective, randomized study was carried out to monitor any added beneficial effect on bone mineral density when hormone-replacement therapy (HRT) was combined with etidronate. PATIENTS AND METHODS: Fifty-eight early postmenopausal women attending metabolic bone disease outpatient clinics were randomly allocated into four treatment groups and monitored for up to 4 years. All patients received 1.0 g/d of elemental calcium. In addition, group 1 received percutaneously administered HRT (n = 15); group 2, intermittent cyclical etidronate (ICE) (n = 14); group 3, HRT and ICE (n = 15); and group 4, calcium alone (n = 14). The bone mineral density (measured by dual-energy x-ray absorptiometry), biochemical variables of bone turnover, including bone-specific alkaline phosphatase, and urinary hydroxyproline:creatinine ratios were measured before treatment and at 2 and 4 years after treatment. RESULTS: In patients who received the combined therapy, bone mineral density was increased in the vertebrae by 10.9% (P < 0.001) and in the femora by 7.25% (P < 0.001) at 4 years. For patients treated with ICE, the increase was 6.79% (P < 0.001) and 1.20% (P < 0.05), and with HRT, 6.78% (P < 0.001) and 4.01% (P < 0.01) in the vertebrae and femora, respectively. The group treated with calcium alone lost 3.81% (P < 0.01) and 4.96% (P < 0.01) of bone mineral density in vertebrae and femora. Patients who received no specific therapy lost 8.58% (P < 0.01) from vertebrae, and 7.83% (P < 0.01) from the femora over 4 years. Patients who received combined therapy had significantly higher bone mineral density in both vertebrae (P < 0.05) and femora (P < 0.01), in comparison to patients who were treated with HRT, or ICE, alone. Three of 9 patients (33%) in the ICE group developed osteomalacia, as shown by bone histomorphometry, whereas in women who received combined HRT and ICE therapies, none of the 11 patients tested had evidence of bone mineralization defects. CONCLUSION: This 4-year, prospective, randomized study in early postmenopausal women showed an additive effect of ICE and HRT on the bone mineral density in both vertebrae and the hip. Furthermore, the combined therapy prevented the occurrence of osteomalacia associated with etidronate. This is the first study to demonstrate the effects of etidronate in early postmenopausal women, and the additive beneficial effects of HRT and ICE on bone mineral density.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Analysis_of_Variance_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Densitometry__X-Ray_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Synergism_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Etidronic_Acid_MeSH S_administration_&_dosage_MeSH Etidronic_Acid_administration_&_dosage_MeSH S_adverse_effects_MeSH Etidronic_Acid_adverse_effects_MeSH S_pharmacology_MeSH Etidronic_Acid_pharmacology_MeSH M_Female_MeSH M_Hip_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Prospective_Studies_MeSH M_Spine_MeSH 
****** 7616869
----K E
----T A comparative study of two hormone replacement therapy regimens on safety and efficacy variables.
----A OBJECTIVE: To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. METHODS: In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups. RESULTS: Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. CONCLUSIONS: Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Anabolic_Agents_MeSH S_administration_&_dosage_MeSH Anabolic_Agents_administration_&_dosage_MeSH S_adverse_effects_MeSH Anabolic_Agents_adverse_effects_MeSH M_Cervix_Uteri_MeSH S_cytology_MeSH Cervix_Uteri_cytology_MeSH S_drug_effects_MeSH Cervix_Uteri_drug_effects_MeSH M_Comparative_Study_MeSH M_Endometrium_MeSH S_cytology_MeSH Endometrium_cytology_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Lipoproteins_MeSH S_blood_MeSH Lipoproteins_blood_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH S_adverse_effects_MeSH Norpregnenes_adverse_effects_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vagina_MeSH S_cytology_MeSH Vagina_cytology_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH 
****** 7473442
----K E
----T Efficacy of oral micronized progesterone in the treatment of luteal phase defects.
----A OBJECTIVE: Vaginal progesterone suppositories are an accepted treatment for infertility attributed to luteal phase defects. Although oral micronized progesterone may be preferable to suppositories for many patients, there are no studies on its use for patients with luteal phase defects. This study evaluated the efficacy of oral micronized progesterone for the treatment of luteal phase defects. STUDY DESIGN: Seven women with luteal phase defects previously corrected by vaginal suppositories were administered oral micronized progesterone (200 mg by mouth three times a day). Endometrial biopsies were performed to evaluate treatment efficacy. Questionnaires were used to assess side effects, including sedation. RESULTS: On oral micronized progesterone, all patients had in-phase endometrial biopsies. Despite complaints of drowsiness, the majority of patients preferred the oral formulation over the vaginal route of administration. CONCLUSION: We conclude that oral micronized progesterone is efficacious in the treatment of luteal phase defects.
----P Journal_Article 
----M M_Administration__Oral_MeSH M_Capsules_MeSH M_Comparative_Study_MeSH M_Female_MeSH M_Human_MeSH P_Luteal_Phase_MeSH M_Pessaries_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_adverse_effects_MeSH S_blood_MeSH Progesterone_blood_MeSH M_Treatment_Outcome_MeSH 
****** 8538478
----K I
----T Efficacy and tolerance of Menorest compared to Premarin in the treatment of postmenopausal women. A randomised, multicentre, double-blind, double-dummy study.
----A Two-hundred and fourteen (214) menopausal women with moderate to severe vasomotor symptoms, aged 40-65 years, were randomised. After a 4-week treatment-free period, each women received a continuous regimen of Menorest 50 twice weekly or Premarin 0.625 mg daily, for 12 weeks. Didrogesterone 10 mg was also given to all women for 12 days of every 28-day cycle. The objectives were to compare the efficacy and safety profiles of Menorest and an oral estrogen. A statistically significant reduction in the mean number of hot flushes occurred in each group compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in the Menorest group, and from 6.7 to 0.5 in the oral estrogen group; there was no statistically significant difference between the two groups (P = 0.36). With each successive treatment cycle, there was a continuous improvement in the number of hot flushes. The incidence and severity of menopausal symptoms were reduced in the same manner in both groups. There were no statistically significant differences in the mean plasma estradiol and estrone concentrations between the two treatment groups after 10 weeks of therapy. The mean estradiol to estrone ratio was similar in both groups, as was the number of adverse events observed. In summary, Menorest was as effective as an oral estrogen in alleviating menopausal symptoms.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Climacteric_MeSH S_blood_MeSH Climacteric_blood_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Tolerance_MeSH M_Dydrogesterone_MeSH S_administration_&_dosage_MeSH Dydrogesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Dydrogesterone_adverse_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 7502689
----K I
----T Prospective evaluation of calcium and estrogen administration on bone mass and metabolism after ovariectomy.
----A We evaluated the effects of low-dose ethinylestradiol administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from surgery, patients received either a sole calcium supplementation 500 mg/day (n = 20) or ethinylestradiol 20 micrograms/day in addition to the same daily calcium supplement (n = 21), for 12 months. In the control group, urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels presented a substantial (p < 0.05) increase, while radial bone density significantly (p < 0.05) decreased 6 months after surgery. In the ethinylestradiol-treated group, the patterns of biochemical markers indicated that ethinylestradiol can restrain the bone remodelling processes. Radial bone density showed no significant modification during the 12 months' study period. In conclusions, these results demonstrate that the administration of 20 micrograms/day of ethinylestradiol can prevent the rapid bone loss that follows ovariectomy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Bone_and_Bones_MeSH S_drug_effects_MeSH Bone_and_Bones_drug_effects_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH S_pharmacology_MeSH Calcium_pharmacology_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Estradiol_Congeners_MeSH S_administration_&_dosage_MeSH Estradiol_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_Congeners_therapeutic_use_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Ethinyl_Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Hydroxyproline_MeSH S_urine_MeSH Hydroxyproline_urine_MeSH M_Middle_Aged_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Ovariectomy_MeSH S_adverse_effects_MeSH Ovariectomy_adverse_effects_MeSH M_Prospective_Studies_MeSH M_Radius_MeSH S_physiology_MeSH Radius_physiology_MeSH M_Time_Factors_MeSH 
****** 8550780
----K E
----T Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women.
----A The present study was undertaken to determine whether the addition of an androgen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption. Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion of the bone resorption markers, deoxypyridinoline, pyridinoline, and hydroxyproline. Patients treated with CEE showed decreases in the serum markers of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C-terminal procollagen peptide. In contrast, subjects treated with E+A showed increases in these markers of bone formation. CEE increased, and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels. Only CEE significantly reduced low density lipoproteins. Both regimens were effective in reducing postmenopausal somatic symptoms, but only E+A had a significant effect on psychological symptoms. We conclude that short term administration of androgen with estrogen may reverse the inhibitory effects of estrogen on bone formation. Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and androgen and whether this results in greater increases in bone mass and strength.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Androgens_MeSH S_administration_&_dosage_MeSH Androgens_administration_&_dosage_MeSH S_pharmacology_MeSH Androgens_pharmacology_MeSH M_Bone_Development_MeSH S_drug_effects_MeSH Bone_Development_drug_effects_MeSH M_Bone_Resorption_MeSH S_metabolism_MeSH Bone_Resorption_metabolism_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Comparative_Study_MeSH M_Drug_Therapy__Combination_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 8569016
----K E
----T Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.
----A OBJECTIVE--To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. DESIGN--A 3-year multicenter, randomized, double-masked, placebo-controlled trial. PARTICIPANTS--A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy. INTERVENTION--Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days. OUTCOME MEASURE--Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy. ANALYSIS--Intention to treat. RESULTS--During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (P < .001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (P = .16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P < .001) and curettages (17.6% vs 0.8%; P < .001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (P = .38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n = 2) or hysterectomy with (n = 2) or without (n = 6) prior medical therapy, or refused further biopsies (n = 1). One woman developed adenocarcinoma of the endometrium while receiving placebo. CONCLUSIONS--At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Biopsy_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Therapy__Combination_MeSH M_Endometrial_Hyperplasia_MeSH S_chemically_induced_MeSH Endometrial_Hyperplasia_chemically_induced_MeSH S_pathology_MeSH Endometrial_Hyperplasia_pathology_MeSH M_Endometrial_Neoplasms_MeSH S_chemically_induced_MeSH Endometrial_Neoplasms_chemically_induced_MeSH S_pathology_MeSH Endometrial_Neoplasms_pathology_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_pharmacology_MeSH Progesterone_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH S_pharmacology_MeSH Progestins_pharmacology_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 8597678
----K E
----T Randomised comparison of oestrogen versus oestrogen plus progestogen hormone replacement therapy in women with hysterectomy. Medical Research Council's General Practice Research Framework.
----A OBJECTIVE: To compare the acceptability and symptomatic and metabolic effects of two regimens of hormone replacement therapy in women with hysterectomy. DESIGN: Randomised, double blind comparison. SETTING: Seven group practices in the Medical Research Council's general practice research framework. SUBJECTS: 321 women with hysterectomy aged 35-59. INTERVENTIONS: Hormone replacement therapy with (a) conjugated equine oestrogen 625 micrograms daily alone or (b) conjugated equine oestrogen 625 micrograms daily plus the progestogen norgestrel 150 micrograms daily for the last 12 days of the 'cycle.' MAIN OUTCOME MEASURES: Changes in blood pressure, weight, symptoms, and haemostatic and lipid values. RESULTS: After two years 36% (57/158) of women randomly allocated to take oestrogen alone had discontinued treatment as compared with 30% (49/163) of women allocated to take oestrogen plus progestogen. Smokers were more likely to withdraw than non-smokers. There were no clear differences between the two groups in symptoms often attributed to hormone replacement therapy or in blood pressure or weight. At one year low density lipoprotein cholesterol concentrations had fallen substantially in both groups. High density lipoprotein cholesterol concentrations rose to significantly higher values in women taking oestrogen alone compared with those taking oestrogen plus progestogen, though triglyceride concentrations and factor VII activity were also significantly higher in this group. Fibrinogen concentration tended to fall, though not significantly, in both groups, possibly more in women taking oestrogen alone. CONCLUSIONS: Oestrogen plus progestogen was no less well tolerated than oestrogen alone. There was a fairly even balance between possibly beneficial and adverse effects of the two regimens on lipid concentrations and coagulability. Concern that the combined regiment may not have the cardioprotective effects ascribed to oestrogen alone can to some extent be allayed, with reassurance for the growing numbers of women with intact uteri using the combined regiment. Misgivings about the combined regiment in women with hysterectomy on the grounds of its acceptability and its effects on lipid values may also be unfounded.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Blood_Pressure_MeSH M_Body_Weight_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Hemostasis_MeSH M_Human_MeSH P_Hysterectomy_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 8695969
----K I
----T Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal, bone-active drug ipriflavone.
----A Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and tolerability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3 +/- 0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n = 24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n = 31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n = 28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%; p < 0.01). Both valid completers and intention to treat analyses revealed a significant difference (p < 0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Bone_Remodeling_MeSH M_Climacteric_MeSH S_physiology_MeSH Climacteric_physiology_MeSH M_Drug_Therapy__Combination_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Forearm_MeSH S_physiopathology_MeSH Forearm_physiopathology_MeSH M_Human_MeSH M_Isoflavones_MeSH S_administration_&_dosage_MeSH Isoflavones_administration_&_dosage_MeSH S_adverse_effects_MeSH Isoflavones_adverse_effects_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Time_Factors_MeSH M_Treatment_Outcome_MeSH 
****** 8657828
----K E
----T Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression.
----A In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Brain_Mapping_MeSH M_Delayed-Action_Preparations_MeSH M_Depression_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH S_etiology_MeSH Depression_etiology_MeSH M_Double-Blind_Method_MeSH M_Electroencephalography_MeSH S_drug_effects_MeSH Electroencephalography_drug_effects_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_biosynthesis_MeSH Follicle_Stimulating_Hormone_biosynthesis_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Multivariate_Analysis_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH 
****** 8707404
----K I
----T Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy--long-term follow-up of a Swedish cohort.
----A We analyzed cancer incidence and mortality in a cohort of 22,597 Swedish women who were prescribed replacement hormones. After 13 years of follow-up in national registries, 2,330 incident cancer cases and 848 cancer deaths were observed. Overall, our results were reassuring since incidence rate ratios (SIRs) for 16 cancer sites and mortality ratios (SMRs) for all 10 examined sites were at, or lower than, unity. However, we found that exposure to an estrogen-progestin combined brand was associated with an increasing relative risk of breast cancer with follow-up time, the SIR reaching 1.4 (95% CI 1.1-1.8) after 10 years of follow-up. The relative risk of endometrial cancer was substantially increased, with the highest SIR of 5.0 (95% CI 1.6-5.9) in women prescribed estrogens alone, whereas those given an estrogen-progestin combination showed no elevation in risk. The risk estimates for liver and biliary tract cancers and for colon cancer were reduced by about 40%, notably in women prescribed the estradiol-progestin compound. Further detailed analyses revealed no evidence of adverse or protective effects on the risk of ovarian, uterine cervical, vulvar/vaginal, rectal, pancreatic, renal, lung, thyroid and other endocrine cancers, brain tumors, malignant melanoma or other skin cancers. Hormone replacement therapy was not associated with an increase in mortality for any cancer site, at this time of follow-up. For breast and endometrial cancers, SMRs were below baseline but tended to increase with follow-up time. We conclude that hormone replacement increases the endometrial-cancer risk after unopposed estrogens and the breast-cancer risk-notably after estrogen-progestin combined therapy-and tentatively suggest that it exerts a protective effect against colon and liver cancer risks.
----P Journal_Article 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_chemically_induced_MeSH Breast_Neoplasms_chemically_induced_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH S_mortality_MeSH Breast_Neoplasms_mortality_MeSH M_Cohort_Studies_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Genital_Neoplasms__Female_MeSH S_chemically_induced_MeSH Genital_Neoplasms__Female_chemically_induced_MeSH S_epidemiology_MeSH Genital_Neoplasms__Female_epidemiology_MeSH S_mortality_MeSH Genital_Neoplasms__Female_mortality_MeSH M_Human_MeSH M_Incidence_MeSH M_Middle_Aged_MeSH M_Neoplasms_MeSH S_chemically_induced_MeSH Neoplasms_chemically_induced_MeSH S_epidemiology_MeSH Neoplasms_epidemiology_MeSH S_mortality_MeSH Neoplasms_mortality_MeSH M_Progestins_MeSH S_adverse_effects_MeSH Progestins_adverse_effects_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Registries_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Sweden_MeSH S_epidemiology_MeSH Sweden_epidemiology_MeSH M_Time_Factors_MeSH 
****** 8746878
----K E
----T Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study.
----A Two-hundred and five (205) menopausal women with moderate to severe vasomotor symptoms, aged 39-64 years, were randomized from 20 clinical centers. After a 4-week treatment-free period, each woman received a cyclical regimen (25 days of a 4-week cycle) of Menorest 50, a new matrix-type transdermal estradiol system or Estraderm TTS 50, a marketed reservoir-type transdermal estradiol system twice weekly for 12 weeks. An oral progestin was also given for 10 days each cycle. The objectives were to compare local and systemic tolerability and efficacy in the treatment of menopausal symptoms. One-hundred and ninety-four [194] patients (96 and 98 patients in the Menorest 50 and the reservoir transdermal patch groups, respectively) were considered in the intent-to-treat population and 204 (102 in each group) in the safety population. The two treatment groups were comparable with regard to the demographic data and menopausal status. The primary efficacy criteria were the comparison between Menorest 50 and the reservoir transdermal patch in erythema and pruritus at application sites and the difference between the treatment groups in the mean number of hot flushes per day at week 12, adjusted for baseline. A statistically significant reduction in the mean number of hot flushes was observed in each group compared with baseline, with a decrease from 6.5 at baseline to 0.3 at 12 weeks and 6.4 to 0.4 in the Menorest 50 and reservoir transdermal patch groups respectively; there was no statistically significant difference between the two groups during the 12-week treatment. The severity score of menopausal symptoms was also dramatically improved in each of the two treatment groups. There were no statistically significant differences in the mean plasma estradiol concentrations and mean estradiol to estrone ratio (> 1.0) in both groups after 10 weeks of therapy. A similar number of adverse events was observed in both groups. Menorest 50 showed better local tolerability than the reservoir transdermal patch with a lower incidence of topical adverse events, erythema and pruritus. In summary, Menorest 50 was as effective as the reservoir transdermal patch in reducing the mean number of hot flushes, and improving the severity of other menopausal symptoms, including vasomotor, psychiatric and urogenital symptoms.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH 
****** 8794418
----K E
----T Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women.
----A OBJECTIVES: This study was designed to evaluate the efficacy of Replens, a non-hormonal moisturizing vaginal gel, on symptoms of vaginal atrophy in postmenopausal women, in comparison with Dienoestrol (Cilag), an oestrogenic vaginal cream. METHODS: Thirty-nine patients were randomly allocated to either of the two treatments. Replens was given three times a week during the 12 weeks of the study, while Dienoestrol was administered daily during the first 2 weeks and thereafter three times a week. Vaginal dryness index, itching, irritation, dyspareunia, pH and safety were evaluated every week the first month and every month thereafter. RESULTS: Both treatments had a significant increase on vaginal dryness index as soon as the first week of treatment, and the hormonal compound was significantly better than the non-hormonal one. All symptoms such as itching, irritation and dyspareunia significantly decreased or disappeared without any difference between the two treatments. For pH, no significant difference was seen either in each group or between the two groups. No adverse events related with the two drugs were found. CONCLUSION: This study shows that Replens applied vaginally three times a week, is a full therapy for all symptoms of vaginal atrophy as well as local estrogen. No serious adverse event was related. Replens is an alternative treatment to local estrogen and perhaps a good complement of systemic HRT in patient suffering from vaginal dryness.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Atrophy_MeSH S_drug_therapy_MeSH Atrophy_drug_therapy_MeSH M_Comparative_Study_MeSH M_Dienestrol_MeSH S_administration_&_dosage_MeSH Dienestrol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Lubrication_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Vagina_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Creams__Foams_and_Jellies_MeSH S_administration_&_dosage_MeSH Vaginal_Creams__Foams_and_Jellies_administration_&_dosage_MeSH M_Vaginal_Diseases_MeSH S_drug_therapy_MeSH Vaginal_Diseases_drug_therapy_MeSH 
****** 8794428
----K I
----T Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass.
----A OBJECTIVE: To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies. METHODS: A total of 104 naturally or surgically postmenopausal women were studied, and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass, a factor overlooked in several studies. They were randomized into four groups of 26 patients each: the untreated control group (mean age 50 +/- 5 years); the hormonal replacement treatment (HRT) group (mean age 48 +/- 6 years), which was treated for 24 days each month with transdermal 17 beta-estradiol, 50 mg/day, together with medroxiprogesterone, 10 mg during 12 days; the calcium group (mean age 50 +/- 4 years), which was treated with elemental calcium, 1 g/day; and the calcitonin group (mean age 50 +/- 5 years), which was treated for 10 days each month with eel calcitonin, 40 IU/day and with elemental calcium, 500 mg/day. Full-body bone densitometry, for measuring total body bone mineral content (TBBMC), was carried out in all the women at baseline and 1 year. TBBMC was corrected for body weight by dividing its value by body weight (TBBMC/W). RESULTS: After 1 year TBBMC/W was lower in every group: -2.14% (P < 0.001) in the control group; -0.14% (P = NS) in the HRT group (P < 0.05 vs. controls); -0.18% (P = NS) in the calcium group (P < 0.05 vs. controls); and -0.06% (P = NS) in the calcitonin group (P < 0.01 vs. controls; P < 0.05 vs. calcium and HRT). CONCLUSIONS: These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M P_Bone_Density_MeSH M_Calcitonin_MeSH S_therapeutic_use_MeSH Calcitonin_therapeutic_use_MeSH M_Calcium_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH M_Comparative_Study_MeSH M_Densitometry__X-Ray_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_epidemiology_MeSH Osteoporosis__Postmenopausal_epidemiology_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH 
****** 8794442
----K E
----T A randomized, double-blind, multicentre study comparing the clinical effects of two sequential estradiol-progestin combinations containing either desogestrel or norethisterone acetate in climacteric women with estrogen deficiency symptoms.
----A OBJECTIVES: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. METHODS: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days. RESULTS: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred. CONCLUSIONS: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Desogestrel_MeSH S_administration_&_dosage_MeSH Desogestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Desogestrel_adverse_effects_MeSH S_therapeutic_use_MeSH Desogestrel_therapeutic_use_MeSH M_Double-Blind_Method_MeSH M_Endometrial_Hyperplasia_MeSH S_prevention_&_control_MeSH Endometrial_Hyperplasia_prevention_&_control_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Patient_Compliance_MeSH M_Physical_Fitness_MeSH M_Placebos_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Sweating_MeSH S_drug_effects_MeSH Sweating_drug_effects_MeSH M_Uterine_Hemorrhage_MeSH S_prevention_&_control_MeSH Uterine_Hemorrhage_prevention_&_control_MeSH 
****** 8841224
----K I
----T Efficacy and local tolerance of a low-dose, 7-day matrix estradiol transdermal system in the treatment of menopausal vasomotor symptoms.
----A OBJECTIVE: To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17 beta-estradiol (E2) daily for 7 days for the relief of vasomotor symptoms. METHODS: A total of 324 surgically or naturally menopausal women, all with prior hysterectomy and moderate to severe vasomotor symptoms (56-140 hot flushes per week, with episodes of sweating, during a baseline observation period), participated in two independent, 12-week, randomized, double-blind, placebo-controlled studies. After a 4-week, treatment-free period, each woman received a continuous regimen of either one E2 transdermal system, two E2 transdermal systems, or placebo transdermal system(s) applied every week for 12 weeks. Efficacy was measured as reduction in hot flush frequency, determined from subject diaries. To measure local tolerance, skin irritation (erythema and edema) was objectively and systematically evaluated under blue light after removal of the transdermal system(s). Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1, 9, 30, 58, 79, and 84. RESULTS: Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week (84% decrease) after 12 weeks of transdermal E2 treatment. Compared with placebo, the decrease in hot flush frequency was significant as early as weeks 2 and 3, and was maintained through the end of the study. Few clinically significant skin reactions occurred, and only nine (3%) of the subjects withdrew because of a skin effect. After initial increase, serum E2 concentrations remained stable throughout the study, achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems, respectively. CONCLUSION: The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therapy and was very well tolerated. The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens, but at lower serum E2 concentrations. This result may be due to the stable E2 blood level achieved with this transdermal system.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Climacteric_MeSH S_blood_MeSH Climacteric_blood_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH 
****** 8844631
----K I
----T A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17 beta combined with an oral progestin on quality of life in postmenopausal women.
----A OBJECTIVE: To compare the effect of transdermal estradiol-17 beta and oral conjugated equine estrogen when combined with an oral progestin on quality of life in post-menopausal women. DESIGN: Randomized controlled double-blind trial. A randomization error lead to the exclusion of six subjects but the soundness of the remaining randomization was confirmed. SETTING: Large urban community. PATIENTS: Women 2-7 years after menopause with a uterus and ovaries, and not currently using hormone replacement therapy. Seventy-four women completed the trial. INTERVENTIONS: After baseline measures of quality of life, subjects were randomly assigned to either continuous oral conjugated equine estrogen 0.625 mg daily or continuous transdermal estradiol-17 beta 50 mcg twice weekly, for four 4-week cycles. Medroxyprogesterone acetate 10 mg oral tablets was administered to both groups for the last 12 days of each cycle. OUTCOMES MEASURED: Quality of life was determined using the Menopause-Specific Quality of Life Questionnaire. Tolerability was determined by a specifically designed list of adverse effects. Both measures were recorded at base-line and in mid-cycle during the second, third and fourth cycles of treatment. RESULTS: There were no statistically significant differences in any of the domains at baseline between the oral and transdermal treatment groups. In the vasomotor domain-scores for the oral and transdermal groups improved from baseline levels of 3.14 and 3.09, respectively, to 1.32 and 1.23; physical domain scores improved from 2.45 and 2.73 to 2.04 and 1.78; psychosocial domain scores improved from 2.72 and 3.04 to 2.21 and 1.94; sexual domain scores improved from 2.32 and 2.16 to 1.64 and 1.30. There were no statistically significant group differences or time/group interactions. Both forms of therapy were equally well tolerated. CONCLUSIONS: Improvement in all domains, measured by the Menopause-Specific Quality of Life Questionnaire, was observed in both the oral and transdermal groups. In the absence of a placebo control group, the improvements observed cannot be attributed solely to the therapy. Neither form of therapy offered an advantage over the other in respect to improvement in quality of life.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Attitude_to_Health_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH S_psychology_MeSH Postmenopause_psychology_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH P_Quality_of_Life_MeSH M_Sexual_Behavior_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH 
****** 8861084
----K E
----T 17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy.
----A OBJECTIVES: To evaluate low doses of 17 beta-estradiol (E2) and norethisterone acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their effects on vasomotor symptoms, bleeding episodes, endometrial histology and mastalgia. METHOD: Sixty postmenopausal women were randomly allocated to three treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was 1 year. RESULTS: A similar statistically significant reduction of climacteric symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings, occurred most commonly during the first treatment months. Fewer bleeding episodes and a higher percentage of amenorrhea was noted in group B compared to the other groups but did not reach statistical significance. All endometrial biopsies showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05) compared to group C, given higher doses of steroids. CONCLUSION: Postmenopausal women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a marked reduction of climacteric complaints and good bleeding control. No endometrial proliferation was detected after 1 year of treatment. This type of therapy may be beneficial especially for elderly women, in whom bleeding may be annoying.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Amenorrhea_MeSH S_drug_therapy_MeSH Amenorrhea_drug_therapy_MeSH S_physiopathology_MeSH Amenorrhea_physiopathology_MeSH M_Atrophy_MeSH S_complications_MeSH Atrophy_complications_MeSH S_pathology_MeSH Atrophy_pathology_MeSH S_physiopathology_MeSH Atrophy_physiopathology_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Therapy__Combination_MeSH M_Endometrium_MeSH S_pathology_MeSH Endometrium_pathology_MeSH S_physiopathology_MeSH Endometrium_physiopathology_MeSH M_Estradiol_MeSH S_standards_MeSH Estradiol_standards_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_standards_MeSH Estrogen_Replacement_Therapy_standards_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_standards_MeSH Norethindrone_standards_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Progesterone_Congeners_MeSH S_standards_MeSH Progesterone_Congeners_standards_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_drug_therapy_MeSH Uterine_Hemorrhage_drug_therapy_MeSH S_etiology_MeSH Uterine_Hemorrhage_etiology_MeSH S_physiopathology_MeSH Uterine_Hemorrhage_physiopathology_MeSH M_Vasomotor_System_MeSH S_physiology_MeSH Vasomotor_System_physiology_MeSH 
****** 8892713
----K I
----T Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI.
----A OBJECTIVE: To assess the effects of hormone therapy on bone mineral density (BMD) in the spine and hip of postmenopausal women. DESIGN: A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial. PARTICIPANTS: A total of 875 healthy women aged 45 to 64 years recruited at 7 clinical centers. INTERVENTIONS: Treatments were (1) placebo; (2) conjugated equine estrogens (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus MPA, 2.5 mg/d daily; or (5) CEE, 0.625 mg/d plus micronized progesterone (MP), 200 mg/d for 12 d/mo. MAIN OUTCOME MEASURES: Bone mineral density at baseline, 12 months, and 36 months. RESULTS: Participants assigned to the placebo group lost an average of 1.8% of spine BMD and 1.7% of hip BMD by the 36-month visit, while those assigned to active regimens gained BMD at both sites, ranging from 3.5% to 5.0% mean total increases in spinal BMD and a mean total increase of 1.7% of BMD in the hip. Changes in BMD for women assigned to active regimens were significantly greater than those assigned to placebo. Women assigned to CEE plus continuous MPA had significantly greater increases in spinal BMD (increase of 5%) than those assigned to the other 3 active regimens (average increase, 3.8%). Findings were similar among those adhering to assigned therapy, although, among adherent participants, there were no significant differences in BMD changes among the 4 active treatment groups. Older women, women with low initial BMD, and those with no previous hormone use gained significantly more bone than younger women, women with higher initial BMD, and those who had used hormones previously. CONCLUSIONS: Postmenopausal women assigned to placebo demonstrated decreased BMD at the spine and hip, whereas women assigned to estrogen therapy increased BMD during a 36-month period. These findings demonstrate that estrogen replacement therapy increases BMD at clinically important sites.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Densitometry__X-Ray_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Fractures_MeSH M_Hip_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Spine_MeSH M_Statistics_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 8892714
----K I
----T The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). A randomized controlled trial.
----A OBJECTIVE: To compare the effect of continuous norethindrone acetate (NA)-ethinyl estradiol (EE2) combinations with matching unopposed EE2 or placebo. DESIGN: A 2-year, double-blind, placebo-controlled, parallel-group clinical trial. SETTING: Outpatients at 65 centers. PATIENTS: Asymptomatic or mildly symptomatic women aged 40 years or older who had undergone the onset of spontaneous menopause within the last 5 years and who had an intact uterus. INTERVENTIONS: Patients were equally randomized to placebo or 1 of 8 treatment groups: 0.2 mg of NA and 1 microg of EE2; 0.5 mg of NA and 2.5 microg of EE2; 1 mg of NA and 5 microg of EE2; 1 mg of NA and 10 microg of EE2; 1 microg of EE2; 2.5 microg of EE2; 5 microg of EE2; or 10 microg of EE2. PRIMARY OUTCOME MEASURES: Bone mineral density (BMD) measured by quantitative computed tomography, serum lipids, and endometrial effects as assessed by rate of hyperplasia and proliferative status. RESULTS: Twelve hundred sixty-five patients entered the study. Bone mineral density increased significantly from baseline (P<.001) in the 1 mg NA-5 microg EE2 and the 1 mg NA-10 microg EE2 treatment groups at each annual assessment. Among the unopposed EE2 groups, only the 10-microg group had increased BMD above baseline, but also was accompanied by an unacceptably high rate of endometrial hyperplasia. The NA-EE2 treatment groups had a significant linear dose-response trend for increasing BMD. Increased endometrial proliferation and hyperplasia occurred with increasing unopposed estrogen doses. The combination of NA and EE2 effectively protected the endometrium against hyperplasia. The percentage of change in the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol was positive for all treatment groups. The increase in triglyceride levels associated with EE2 was attenuated with NA-EE2 treatment. CONCLUSIONS: Daily treatment with NA-EE2 was well tolerated and protected the endometrium from EE2-induced proliferation and hyperplasia. The NA-EE2 treatments produced a dose-related significant increase in BMD that was not present with unopposed EE2 treatment. The overall effect of NA-EE2 treatments on lipid measures was favorable.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH P_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Endometrial_Hyperplasia_MeSH S_pathology_MeSH Endometrial_Hyperplasia_pathology_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_Congeners_MeSH S_administration_&_dosage_MeSH Estradiol_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_Congeners_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Ethinyl_Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Statistics_MeSH 
****** 8905602
----K I
----T A randomized, double-blind, placebo-controlled, crossover study on the effect of oral oestradiol on acute menopausal symptoms.
----A Acute menopausal symptoms occur less frequently in Asian than in Caucasian women. Oestrogen replacement therapy has been shown to be effective in controlling acute symptoms in Caucasians, but the effect of oestrogens is not well documented in Asian women. A randomized, double-blind, placebo-controlled, crossover study of the effect of oral oestradiol on the incidence of acute menopausal symptoms was conducted in 83 Hong Kong Chinese women who had experienced a surgical menopause. Although there was a significant increase in the oestradiol concentration with treatment compared with placebo (P < 0.001), there were no significant differences in the reporting of symptoms between the treatment and placebo groups. There is no obvious explanation for this apparent lack of effect of oestrogen on acute menopausal symptoms in Chinese women. Whilst it may be related to the generally low incidence of symptoms or to a higher dietary intake of phytoestrogens in Chinese women, further studies are necessary to explain these findings.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hong_Kong_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Treatment_Outcome_MeSH 
****** 8943507
----K E
----T Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone.
----A Two progesterone presentations, a vaginal application of 90 mg progesterone per day (Crinone) or 300 mg progesterone administered orally (Utrogestan), were compared for luteal phase support of patients undergoing an in-vitro fertilization (IVF) procedure. A total of 283 patients were randomly allocated to either treatment. The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation. Efficacy was assessed using the pregnancy and delivery rates. Safety was assessed through specific symptoms and usual safety monitoring. The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 (Crinone 35.3%, Utrogestan 29.9%, P = 0.55), 30 (Crinone 28.5%, Utrogestan 25.0%, P = 0.61) and 90 (Crinone 25.9%, Utrogestan 22.9%, P = 0.69). No differences in the spontaneous abortion rates were seen thereafter. The delivery rates (number of deliveries per patient; Crinone 23.0%, Utrogestan 22.2%, P = 1.00), as well as the ratio of newborn babies per embryo transferred (Crinone 11.7%, Utrogestan 11.1%, P = 0.91), were not significantly different. Safety parameters were similar in both groups, except for drowsiness, which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points. No serious adverse events were recorded in this study. The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Comparative_Study_MeSH M_Delayed-Action_Preparations_MeSH M_Embryo_Implantation_MeSH M_Female_MeSH P_Fertilization_in_Vitro_MeSH M_Gels_MeSH M_Human_MeSH P_Luteal_Phase_MeSH M_Pregnancy_MeSH M_Pregnancy_Rate_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 8981333
----K E
----T Comparison of two estradiol transdermal systems (Oesclim 50 and Estraderm TTS 50). I. Tolerability, adhesion and efficacy.
----A OBJECTIVES: The objectives were to compare the tolerability, adhesion and efficacy of a new matrix-type estradiol transdermal system, Oesclim 50, with those of Estraderm TTS 50, a reservoir-type system. METHODS: This was an open, randomised, parallel-group, multi-centre clinical trial, performed in six European countries. A total of 143 healthy menopausal women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS 50. The transdermal systems were applied twice weekly for 24 days out of each 28-day cycle, over a period of four cycles. Oral progestogen treatment was taken by non-hysterectomised patients for the last 12 days of estrogen therapy in each cycle. RESULTS: The local skin tolerability of the Oesclim 50 transdermal system was significantly better than that of Estraderm TTS 50. In the Oesclim 50 group, 4.2% of applications caused a reaction, compared with 9.5% in the Estraderm TTS 50 group (P < 0.001). Safety assessments showed both treatments to be well tolerated. Seven patients in the Oesclim 50 group, and 12 in the Estraderm TTS 50 group, discontinued due to adverse events. Of these discontinuations, one (0.7% of patients) in the Oesclim 50 group and seven (5.1% of patients) in the Estraderm TTS 50 group were due to application site reactions (P < 0.05). There was no statistically significant difference between the two groups in the percentage of patients with signs of hyperestrogenism (29 patients (20.3%) in the Oesclim group and 28 patients (20.0%) in the Estraderm TTS 50 group). Adhesion was significantly better for the Oesclim 50 transdermal system, with 6.0% of Oesclim 50 applications becoming detached compared with 11.3% of Estraderm TTS 50 applications (P < 0.001). The greater adhesion of Oesclim 50 was particularly apparent when the systems were exposed to water, with three times fewer Oesclim 50 systems becoming detached during a shower or bath (P < 0.001 in each case). Both treatments produced significant and comparable improvements in vasomotor symptoms, other menopausal symptoms and gynaecological assessments. A near-maximal effect on vasomotor symptoms was observed after approximately 1 month of treatment, and was maintained for the entire treatment period. CONCLUSION: Overall, Oesclim 50 provided statistically significantly better local skin tolerability and adhesion than Estraderm TTS 50, together with comparable efficacy and safety.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Drug_Eruptions_MeSH S_etiology_MeSH Drug_Eruptions_etiology_MeSH M_Drug_Monitoring_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Europe_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 9032742
----K E
----T Effect on sexual life--a comparison between tibolone and a continuous estradiol-norethisterone acetate regimen.
----A OBJECTIVES: to compare the effects of tibolone 2.5 mg (Livial) with those of 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (Kliogest) on sexual life. METHODS: in a 48 week, double blind, multicenter study, 437 postmenopausal women were randomised to treatment with either tibolone or 17 beta-estradiol 2 mg plus norethisterone acetate. Treatment groups were compared with respect to different aspects of sexual life with a questionnaire covering sexual experience and responsiveness during the last 30 days. RESULTS: a total of 315 subjects completed 48 weeks treatment. In the E2/NETA group an improvement after 48 weeks compared to baseline was observed in five out of seven items assessing sexual life. In the tibolone group an improvement regarding all seven items assessing sexual life was seen. When tibolone was compared to E2/NETA significantly higher scores were found for the items assessing 'frequency', 'satisfaction' and 'enjoyment'. CONCLUSIONS: this study indicate that tibolone and E2/NETA -which both have an androgenic profile-affect several aspects of sexual life positively. The difference with respect to satisfaction with sexual enjoyment and frequency could be of clinical importance.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Anabolic_Agents_MeSH S_administration_&_dosage_MeSH Anabolic_Agents_administration_&_dosage_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Estriol_MeSH S_administration_&_dosage_MeSH Estriol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Libido_MeSH S_drug_effects_MeSH Libido_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH M_Sexual_Behavior_MeSH S_drug_effects_MeSH Sexual_Behavior_drug_effects_MeSH 
****** 9032748
----K E
----T Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: a comparison.
----A OBJECTIVE: The objective of this study was to compare the efficacy of locally administered low-dose estrogens (0.625 mg of conjugated estrogens) and orally administered tibolone in postmenopausal women with symptoms and signs of atrophic vaginitis. Vaginal ultrasound was performed for the evaluation of endometrial or ovarian abnormalities. METHODS: A 6-month comparative randomised prospective study of women taking tibolone and locally administered low-dose estrogens. Seventy two postmenopausal women with symptoms of atrophic vaginitis were examined with vaginal ultrasound. The endometrial thickness, the endometrial volume, the uterus and the ovaries were measured before and after 6 months of treatment with low-dose estrogens or tibolone. RESULTS: In group A (low-dose estrogens treatment) the mean endometrial thickness, before and after treatment, was 3.0 +/- 0.1 mm and 2.9 +/- 0.8 mm, respectively. The mean ovarian volume was 3.9 ml. There were no changes in uterine volume during the treatment period. In group B (treated with tibolone) endometrial thickness was 3.2 +/- 0.3 mm and 3.2 +/- 0.7 mm, respectively. One women experienced vaginal bleeding. The volume of corpus uteri was unchanged after treatment. The volume of both ovaries was 4.2 ml and 3.9 ml, respectively. The overall acceptability of both types of administration was good. CONCLUSIONS: This study, using vaginal ultrasound, has shown that either hormone replacement therapy with tibolone or symptomatic treatment with low-dose estrogens, gives no sign of endometrial proliferation measured as endometrial thickness.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Anabolic_Agents_MeSH S_administration_&_dosage_MeSH Anabolic_Agents_administration_&_dosage_MeSH M_Atrophy_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH S_ultrasonography_MeSH Endometrium_ultrasonography_MeSH M_Endosonography_MeSH S_drug_effects_MeSH Endosonography_drug_effects_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH M_Patient_Acceptance_of_Health_Care_MeSH M_Prospective_Studies_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_pathology_MeSH Vagina_pathology_MeSH S_ultrasonography_MeSH Vagina_ultrasonography_MeSH 
****** 9071476
----K I
----T Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra.
----A Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no association between cytokine release and bone mass or loss assessed over 2 yrs. The only exception was a weak estrogen-independent correlation between basal IL-1ra secretion and bone loss (r = -0.21, p < 0.05). Flow cytometry did not confirm a relationship between CD4/CD8 T-cell ratios and bone density or loss, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p < 0.01) similar to that found in patients with established osteoporosis, indicating that these adherent mononuclear cells may be important in the pathophysiology of post-menopausal bone loss. The possibility that IL-1ra acts as an independent bone-sparing factor unrelated to estrogen withdrawal warrants further investigation. In conclusion, ERT maintains bone without affecting the release of the IL-1 family of cytokines in whole blood cultures.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Cross-Sectional_Studies_MeSH M_Cytokines_MeSH S_metabolism_MeSH Cytokines_metabolism_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Interleukin-1_MeSH S_metabolism_MeSH Interleukin-1_metabolism_MeSH M_Longitudinal_Studies_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_immunology_MeSH Osteoporosis__Postmenopausal_immunology_MeSH S_metabolism_MeSH Osteoporosis__Postmenopausal_metabolism_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Receptors__Interleukin-1_MeSH S_metabolism_MeSH Receptors__Interleukin-1_metabolism_MeSH M_Support__Non-U_S__Gov't_MeSH P_T-Lymphocyte_Subsets_MeSH 
****** 9089564
----K I
----T HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.
----A OBJECTIVES: To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. METHODS: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups. RESULTS: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. CONCLUSIONS: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M P_Bone_Density_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH P_Exercise_Therapy_MeSH M_Female_MeSH M_Femur_MeSH S_drug_effects_MeSH Femur_drug_effects_MeSH M_Human_MeSH M_Isometric_Contraction_MeSH S_drug_effects_MeSH Isometric_Contraction_drug_effects_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH S_metabolism_MeSH Lipids_metabolism_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH P_Muscle_Contraction_MeSH S_drug_effects_MeSH Muscle_Contraction_drug_effects_MeSH M_Muscle__Skeletal_MeSH S_drug_effects_MeSH Muscle__Skeletal_drug_effects_MeSH S_physiology_MeSH Muscle__Skeletal_physiology_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Placebos_MeSH P_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Prospective_Studies_MeSH 
****** 9158080
----K I
----T Prevention of postmenopausal bone loss with minimal uterine bleeding using low dose continuous estrogen/progestin therapy: a 2-year prospective study.
----A OBJECTIVE: To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss. DESIGN: A 2-year, prospective, open label, randomized study. SETTING: Department of Obstetrics and Gynecology of a university hospital. PARTICIPANTS: Fifty-two postmenopausal or oophorectomized women. INTERVENTION: One of the following regimens was continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg + medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4) control. MEASUREMENTS: Lumbar spine and femoral BMD by dual energy X-ray absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH, calcitonin. A1-p, and osteocalcin. RESULTS: Of the 52 patients enrolled in this study, 49 patients completed the 1 year of therapy and 36 completed the 2- year study. The control group showed a significant decrease in lumbar BMD over the 2 years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 approximately 12.4%), 7.4% (0.60 approximately 14.2%) and 3.20% (0.61 approximately 5.84%), respectively, and were significantly higher than pretreatment values. The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA. HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA. CONCLUSIONS: Continuous hormone replacement therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_adverse_effects_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH S_prevention_&_control_MeSH Uterine_Hemorrhage_prevention_&_control_MeSH 
****** 9166392
----K I
----T Vitamin D and HRT: no benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study.
----A The study was designed to examine the effect of hormone replacement therapy (HRT) and low-dose bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo-controlled study. The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13100). A total of 464 early postmenopausal women were randomized to four groups: (1) HRT (a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E2Val/CPA); (2) vitamin D3 (cholecalciferol, 300 IU/day); (3) HRT + Vit D; and (4) placebo (calcium lactate; 93 mg Ca2+/day). Lumbar (L1-4) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p > 0.001) and by 1.4% in the HRT + Vit D group (p = 0.002), whereas lumbar BMD had decreased by 3.5% (p < 0.001) in the Vit D group and by 3.7% (p < 0.001) in the placebo group. The loss of femoral neck BMD was lower in the HRT (-0.3%) and the HRT + Vit D (0.9%) groups compared with the Vit D (-2.4%) and the placebo groups (-3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Anthropometry_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Femur_Neck_MeSH S_physiology_MeSH Femur_Neck_physiology_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_physiology_MeSH Lumbar_Vertebrae_physiology_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Prospective_Studies_MeSH M_Vitamin_D_MeSH S_therapeutic_use_MeSH Vitamin_D_therapeutic_use_MeSH 
****** 9177404
----K I
----T The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation.
----A To compare the relative sensitivity and specificity of bone turnover indexes for bone loss or gain in early postmenopausal women, we performed a multicenter trial in 236 menopausal women (mean age, 51 yr), who were randomized to hormone replacement therapy (HRT) or calcium supplementation (CS; 500 mg/day) for 1 yr. Two markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase (BSAP), and two markers of bone resorption, urinary N-telopeptide (NTx) and urinary free deoxypyridinoline (fDpd), as well as spine and femoral neck bone mineral density (BMD) were measured at baseline and 3, 6, and 12 months after treatment. Women receiving HRT (n = 105) showed a significant increase in spine BMD (+2.5%; P < 0.0001) and hip BMD (+1.0%; P = 0.02) compared to women receiving CS, who showed a decline at both sites (-1.1%; P < 0.01). All four markers showed time-dependent decreases in women receiving HRT (P < 0.001) and no change in women receiving CS alone. When baseline indexes of turnover were stratified by quartile, there was a significantly greater increase in BMD among those with the highest NTx, OC, and BSAP levels compared to that in those with the lowest NTx, OC, and BSAP levels (P < 0.05). The highest quartile for percent change from baseline to 6 months in fDpd, BSAP, and NTx was also associated with the greatest change in spine BMD at 1 yr. Receiver operator characteristic curves for percent change from baseline to 6 months in an individual marker to 1 yr change in BMD during HRT revealed that the percent change in NTx provided the greatest discrimination between gain and loss of BMD. When subjects receiving HRT were compared by their positive or negative skeletal response at 1 yr and their baseline turnover marker, initial NTx values were significantly higher in those that gained bone than in those that lost bone (P = 0.0002). CS women in the highest quartile for NTx at baseline had significantly greater decreases in spine BMD than subjects with the lowest NTx values (P < 0.005), although this was not true for fDpd (P < 0.20). In conclusion, for early postmenopausal women there are differential responses of biochemical markers to HRT and CS. Baseline urinary NTx and serum OC were the most sensitive predictors of change in spine BMD after 1 yr of either HRT or CS. Similarly, the percent change in NTx and OC from baseline to 6 months best predicted bone gain or loss. We conclude that markers of bone formation and resorption can be used clinically to predict future BMD in early postmenopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Biological_Markers_MeSH P_Bone_Density_MeSH M_Bone_and_Bones_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Calcium_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_metabolism_MeSH Postmenopause_metabolism_MeSH M_Predictive_Value_of_Tests_MeSH M_Single-Blind_Method_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 9220205
----K E
----T Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996.
----A The endocrine physiology of the climacteric supports a rationale for the concomitant replacement of androgen and estrogen following menopause. Clinical and research experience with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy, suggests that the health benefit offered by androgen replacement exceeds the potential risk when treatment is properly managed. In this review, we concentrate on the effects of oral alkylated androgens. The virilizing effects (e.g., hirsutism, acne, voice change, and alopecia) of oral androgens are typically dose and duration dependent; androgen replacement at doses < or = 10 mg once daily administered for prolonged periods (> 6 months) produces masculinization effects that generally abate with dose reduction or discontinuation of treatment. No clinical sequelae or irreversible pathophysiologic effects have been associated with any virilization that may occur. Changes in lipoprotein metabolism associated with oral estrogen-androgen use include reduced total cholesterol levels and reduced high-density lipoprotein cholesterol levels which may reduce the long-term risk of cardiovascular disease. No clinically identifiable risk with respect to other cardiovascular variables, such as blood pressure, has been associated with the longterm administration of low doses of oral androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and hepatocellular carcinoma are extremely rare at the dose levels of androgen used in hormone replacement therapy, although individual sensitivity to the potential hepatotoxic effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective and prospective studies involving the use of androgens alone and in combination with estrogens demonstrate that concerns about the adverse effects of androgen use associated with supraphysiologic, self-escalated doses in men do not apply to the much lower doses combined with estrogens for hormone replacement in postmenopausal women.
----P Journal_Article Review Review__Tutorial 
----M M_Androgens_MeSH S_adverse_effects_MeSH Androgens_adverse_effects_MeSH S_therapeutic_use_MeSH Androgens_therapeutic_use_MeSH M_Animals_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH 
****** 9252929
----K E
----T Estrogen-androgen for hormone replacement. A review.
----A OBJECTIVE: To critically examine the role of androgens as part of postmenopausal hormone replacement therapy. STUDY DESIGN: Examination of original reports and reviews obtained by electronic database searches and supplemented by manual search of bibliographies. RESULTS: As compared to estrogens alone, estrogen-androgen therapy may better protect against osteoporosis and increase libido, energy levels and general sense of well-being. However, estrogen-androgen replacement also reduces the beneficial increases in high-density lipoprotein induced by estrogens alone, although this effect may be offset at least partially by decreases in atherogenic triglycerides. The long-term net effect of estrogen-androgen replacement on cardiovascular disease remains unknown. CONCLUSION: Although the literature includes relatively few clinical trials or well-controlled studies and is further limited by the subjective nature of outcomes, such as sexual and psychological function, the available data suggest that for many postmenopausal women, estrogen-androgen replacement may provide benefits beyond those provided by estrogen-only replacement therapy.
----P Journal_Article Review Review__Tutorial 
----M M_Affective_Symptoms_MeSH S_drug_therapy_MeSH Affective_Symptoms_drug_therapy_MeSH M_Androgens_MeSH S_administration_&_dosage_MeSH Androgens_administration_&_dosage_MeSH S_adverse_effects_MeSH Androgens_adverse_effects_MeSH S_therapeutic_use_MeSH Androgens_therapeutic_use_MeSH M_Bone_Density_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Libido_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH P_Postmenopause_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 9288701
----K I
----T Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch.
----A OBJECTIVES: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. METHODS: A multicenter, double-blind, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. RESULTS: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6-5.8). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. CONCLUSIONS: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrone_MeSH S_analogs_&_derivatives_MeSH Estrone_analogs_&_derivatives_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Italy_MeSH M_Middle_Aged_MeSH M_Treatment_Outcome_MeSH 
****** 9385494
----K E
----T Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.
----A This paper summarizes all postmarketing safety surveillance data collected by Solvay Pharmaceuticals, Inc. (Marietta, Georgia), between 1989 and 1996 for Estratest and Estratest HS (half-strength). These oral esterified estrogens--methyltestosterone combination products have been marketed in the United States since 1964 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients whose symptoms have not been relieved by estrogens alone. Between 1989 and 1996, more than 1 million woman-years of exposure occurred. The safety profile contained in this paper is based on a cumulative total of 568 individual cases comprising 863 adverse events (AEs). The proportions of AEs associated with the use of Estratest (575 events; 66.6%) and Estratest HS (288 events; 33.4%) were commensurate with the proportions of individual reports of adverse experiences for the two formulations (369 reports [65.0%] and 199 reports [35.0%], respectively). The rank order and percentage of types of AEs reported were also similar. The cumulative volume of reports was relatively low given the extent of exposure. Despite the limitations inherent in spontaneous postmarketing surveillance, the safety profile derived from this assessment does not indicate a significant safety concern with Estratest or Estratest HS. No deaths were reported, and no adverse findings indicative of the need for more comprehensive surveillance or concern on the part of the medical community or consumers were observed. Reports of cancer, cardiovascular disease, thromboembolic phenomena, and hepatic dysfunction were few and were assessed as not related to treatment with Estratest or Estratest HS; reports of drug overdose, drug-drug interaction, and birth defects were rare (4 of 863 events; 0.5%). The most commonly reported AEs were those known to be associated with estrogen therapy (weight gain, headache, nausea, and vasodilatation) and androgen treatment (alopecia, acne, and hirsutism). Twenty-three (4.0%) of the 568 cases reported had at least one event that was regarded as serious, and 53 (6.1%) of the total 863 AEs were regarded as serious. The findings indicate that Estratest and Estratest HS are safe when used as directed and that the marginal increase in risk associated with androgen coadministration can be managed with appropriate patient selection and monitoring, as stated in the package insert for these compounds.
----P Journal_Article 
----M M_Acne_Vulgaris_MeSH S_chemically_induced_MeSH Acne_Vulgaris_chemically_induced_MeSH M_Adult_MeSH M_Adverse_Drug_Reaction_Reporting_Systems_MeSH M_Aged_MeSH M_Alopecia_MeSH S_chemically_induced_MeSH Alopecia_chemically_induced_MeSH M_Comparative_Study_MeSH M_Drug_Combinations_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH M_Female_MeSH M_Hirsutism_MeSH S_chemically_induced_MeSH Hirsutism_chemically_induced_MeSH M_Human_MeSH M_Methyltestosterone_MeSH S_adverse_effects_MeSH Methyltestosterone_adverse_effects_MeSH M_Middle_Aged_MeSH P_Product_Surveillance__Postmarketing_MeSH M_United_States_MeSH 
****** 9391998
----K I
----T Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women.
----A OBJECTIVES: To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate. RESULTS: No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density. CONCLUSION: Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Adult_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Comparative_Study_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Non-Steroidal_MeSH S_pharmacology_MeSH Estrogens__Non-Steroidal_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Isoflavones_MeSH S_pharmacology_MeSH Isoflavones_pharmacology_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Longitudinal_Studies_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Plant_Preparations_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Time_Factors_MeSH 
****** 9443925
----K I
----T Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.
----A BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Alendronate_MeSH S_adverse_effects_MeSH Alendronate_adverse_effects_MeSH S_pharmacology_MeSH Alendronate_pharmacology_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Forearm_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH M_Medroxyprogesterone_MeSH S_pharmacology_MeSH Medroxyprogesterone_pharmacology_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Pelvic_Bones_MeSH S_drug_effects_MeSH Pelvic_Bones_drug_effects_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 9522320
----K E
----T Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.
----A OBJECTIVE: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. METHODS: Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. RESULTS: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. CONCLUSIONS: The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Androgen_Antagonists_MeSH S_administration_&_dosage_MeSH Androgen_Antagonists_administration_&_dosage_MeSH S_therapeutic_use_MeSH Androgen_Antagonists_therapeutic_use_MeSH M_Clonidine_MeSH S_pharmacology_MeSH Clonidine_pharmacology_MeSH M_Cohort_Studies_MeSH M_Comparative_Study_MeSH M_Cyproterone_MeSH S_administration_&_dosage_MeSH Cyproterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Cyproterone_therapeutic_use_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Megestrol_MeSH S_administration_&_dosage_MeSH Megestrol_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Megestrol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Megestrol_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Naloxone_MeSH S_pharmacology_MeSH Naloxone_pharmacology_MeSH M_Narcotic_Antagonists_MeSH S_pharmacology_MeSH Narcotic_Antagonists_pharmacology_MeSH M_Neurosecretory_Systems_MeSH S_drug_effects_MeSH Neurosecretory_Systems_drug_effects_MeSH S_physiology_MeSH Neurosecretory_Systems_physiology_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Sympatholytics_MeSH S_pharmacology_MeSH Sympatholytics_pharmacology_MeSH M_Vaginal_Creams__Foams_and_Jellies_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH S_physiology_MeSH Vasomotor_System_physiology_MeSH M_beta-Endorphin_MeSH S_blood_MeSH beta-Endorphin_blood_MeSH S_drug_effects_MeSH beta-Endorphin_drug_effects_MeSH S_metabolism_MeSH beta-Endorphin_metabolism_MeSH 
****** 9531230
----K I
----T Low-dose esterified estrogen therapy: effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Estratab/Osteoporosis Study Group.
----A BACKGROUND: Prospective studies have shown that doses equivalent to conjugated equine estrogens of 0.625 mg/d or higher are needed to produce a significant increase in bone mineral density of the lumbar spine. OBJECTIVES: To determine the effects of unopposed esterified estrogens on bone mineral density, lipid levels, and endometrial tissue structure, and to relate these effects to changes in plasma estradiol levels. METHODS: Four hundred six postmenopausal women were given calcium, 1000 mg/d, and randomly assigned to receive continuous esterified estrogens (0.3, 0.625, or 1.25 mg/d) or placebo for 24 months. Bone mineral density measurements and endometrial and laboratory assessments were conducted every 6 months; plasma estradiol concentrations were measured after 12, 18, and 24 months. RESULTS: All doses of esterified estrogens produced significant increases in bone mineral density of the lumbar spine compared with baseline and with placebo at 6, 12, 18, and 24 months. Mean plasma estradiol levels increased with esterified estrogens dose, and individual subject bone mineral density changes appeared related to plasma estradiol concentrations. Clinically relevant rates of endometrial hyperplasia were noted only in the groups receiving 0.625 and 1.25 mg of esterified estrogens daily. Lipid changes were dose related and apparent in all groups. CONCLUSIONS: Esterified estrogens at doses from 0.3 to 1.25 mg/d, administered unopposed by progestin, produce a continuum of positive changes on bone and lipids. Plasma estradiol concentrations increased with esterified estrogens dose and were related to positive bone mineral densities. The 0.3-mg dose resulted in positive bone and lipid changes without inducing endometrial hyperplasia.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estradiol_Congeners_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Hyperplasia_MeSH S_chemically_induced_MeSH Hyperplasia_chemically_induced_MeSH M_Incidence_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Spine_MeSH S_drug_effects_MeSH Spine_drug_effects_MeSH S_physiopathology_MeSH Spine_physiopathology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 9552083
----K I
----T A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis.
----A PURPOSE: Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis. PATIENTS AND METHODS: Seventy-two postmenopausal women (mean age 64.9+/-0.5 years) attending metabolic bone disease outpatient clinics with established osteoporosis were randomly allocated into one of four treatment groups and monitored for 4 years. All patients enrolled in this study including the control group (n=18) received 1.0 g elemental calcium and 400 units vitamin D per day. The HRT group (n=18) received cyclical estrogen and progesterone; the etidronate group (n=17) received intermittent cyclical etidronate; and the combined therapy group (n=19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation. In 40 patients (10 patients per group), analysis of bone histomorphometry was carried out after 4 years of treatment. RESULTS: In patients who received the combined therapy, BMD increased in the lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and femora, respectively, after 4 years. Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora (P <0.05) in comparison with patients who were treated with HRT or etidronate alone after 4 years. In comparison with patients in the control group, there was a trend toward a lower rate of new vertebral fractures in the treatment groups. Height loss was significantly less in all three active treatment groups (HRT [P <0.001], etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with the control group. The combined therapy group did not have a significant height loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups. None of the patients had histomorphometric evidence of osteomalacia. CONCLUSION: This 4-year randomized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Etidronic_Acid_MeSH S_therapeutic_use_MeSH Etidronic_Acid_therapeutic_use_MeSH M_Female_MeSH M_Femur_Neck_MeSH S_drug_effects_MeSH Femur_Neck_drug_effects_MeSH S_physiopathology_MeSH Femur_Neck_physiopathology_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH S_physiopathology_MeSH Lumbar_Vertebrae_physiopathology_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH M_Treatment_Outcome_MeSH 
****** 9588696
----K E
----T Acute estradiol and progesterone administration reduced cardiovascular and catecholamine responses to mental stress in menopausal women.
----A Steroid hormones are involved in the regulation of sympathoadrenal activity. Since the effect of sex steroids on the cardiovascular system and catecholamine secretion could also be exerted through an acute, nongenomic mechanism, we have studied the response to mental stress (color word test, CWT) in a group of 15 menopausal women during estrogen (100 microg of estradiol by patch), progesterone (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the curve of SBP was higher during placebo (2,855 +/- 131 mm Hg x min) than during estradiol (2,585 +/- 139 mm Hg x min) and progesterone (2,553 +/- 179 mm Hg x min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental stress was higher during placebo than during estradiol administration (F = 4.3, p < 0.01). The area under the curve of epinephrine was 10,342 +/- 1,348 pmol/min x 1 during placebo and 7,280 +/- 818 pmol/min x 1 during estradiol (p < 0.03). The plasma glycerol levels at the end of CWT were higher during placebo (0.26 +/- 0.04 nmol/l) than during estradiol (0.19 +/- 0.03 mmol/l) and progesterone (0.17 +/- 0.04 mmol/l) administration (p < 0.05 for both). No significant differences were found in the responses of diastolic blood pressure, heart rate, norepinephrine and cortisol to mental stress during placebo and estradiol or progesterone administration. This study demonstrates that acute steroid administration is able to modify the cardiovascular and catecholamine response to mental stress in menopausal women.
----P Clinical_Trial Journal_Article 
----M M_Adrenal_Glands_MeSH S_drug_effects_MeSH Adrenal_Glands_drug_effects_MeSH P_Cardiovascular_Physiology_MeSH M_Catecholamines_MeSH S_secretion_MeSH Catecholamines_secretion_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Progesterone_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Stress__Psychological_MeSH S_drug_therapy_MeSH Stress__Psychological_drug_therapy_MeSH S_physiopathology_MeSH Stress__Psychological_physiopathology_MeSH M_Sympathetic_Nervous_System_MeSH S_drug_effects_MeSH Sympathetic_Nervous_System_drug_effects_MeSH 
****** 9666940
----K I
----T Monitoring estrogen replacement therapy and identifying rapid bone losers with an immunoassay for deoxypyridinoline.
----A We have assessed urinary deoxypyridinoline (Dpd) levels by immunoassay in women who participated in a double-masked, placebo-controlled trial of the bone loss prevention effects of estrogen replacement therapy (ERT). Ninety-one women who had undergone recent surgical menopause were randomized to receive either placebo or 0.025, 0.05 or 0.1 mg/day transdermal 17 beta-estradiol for 2 years. Mean Dpd levels in the postmenopausal women were significantly elevated (p < 0.0001) above mean Dpd levels in a reference population of healthy, premenopausal women. Subjects in the placebo group lost 6.4% of lumbar spine bone mineral density (BMD) and 4.9% of mid-radius bone mineral content (BMC) over 2 years. Dpd levels at baseline were inversely correlated with BMD and BMC changes in the placebo group. The placebo group and subjects receiving 0.025 mg/day 17 beta-estradiol who had Dpd levels increased above the reference interval cut-off (mean + 2 standard deviations, 7.5 nmol/mmol) lost 2 times more bone mass than did those with Dpd levels below it. Dpd levels decreased significantly (p < 0.01) from baseline at 6 months following initiation of treatment with 0.05 or 0.1 mg/day 17 beta-estradiol, changes that correlated with increased lumbar spine BMD and with changes in mid-radius BMC. At 12 months, Dpd levels were lower than baseline and placebo in all three treatment groups. These data suggest utility of this Dpd immunoassay in assessing changes in bone resorption induced by surgical menopause and ERT.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Amino_Acids_MeSH S_urine_MeSH Amino_Acids_urine_MeSH M_Biological_Markers_MeSH S_urine_MeSH Biological_Markers_urine_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_prevention_&_control_MeSH Osteoporosis_prevention_&_control_MeSH S_urine_MeSH Osteoporosis_urine_MeSH M_Time_Factors_MeSH 
****** 9699191
----K E
----T Hormonal and psychological treatment: therapeutic alternative for menopausal women?
----A The purpose of this study was to determine whether psychological support associated with hormone replacement therapy (HRT) was more beneficial than replacement therapy alone. Our findings showed that HRT alone was more effective against vasomotor symptoms than HRT with psychological treatment (PT). While the combination of both treatment modalities (HRT + PT) was more effective against insomnia, nervousness, melancholy, fatigue, palpitations, and vertigo. Hormonal treatment alone and HRT with psychological treatment had little effect against paresthesia or tingling. Neither HRT alone nor HRT with psychological treatment was effective against joint and muscle pain or headache.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Climacteric_MeSH S_psychology_MeSH Climacteric_psychology_MeSH M_Combined_Modality_Therapy_MeSH M_Comparative_Study_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Personality_Inventory_MeSH P_Psychotherapy_MeSH M_Treatment_Outcome_MeSH 
****** 9718051
----K I
----T Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
----A CONTEXT: Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials. OBJECTIVE: To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease. DESIGN: Randomized, blinded, placebo-controlled secondary prevention trial. SETTING: Outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years. INTERVENTION: Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years. MAIN OUTCOME MEASURES: The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered. RESULTS: Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38). CONCLUSIONS: During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Coronary_Disease_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Lipoproteins_MeSH S_blood_MeSH Lipoproteins_blood_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Proportional_Hazards_Models_MeSH M_Risk_MeSH M_Support__Non-U_S__Gov't_MeSH M_Survival_Analysis_MeSH 
****** 9800666
----K E
----T Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses.
----A OBJECTIVE: To investigate the efficacy of esterified estrogens alone and combined with oral androgen on sexual function and menopausal symptoms in postmenopausal women. STUDY DESIGN: Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind, randomized trial in which they received either oral esterified estrogens or esterified estrogens + androgen for eight weeks after a single-blind, placebo, lead-in period. Sexual function was assessed with a questionnaire used in the Yale midlife survey, and plasma levels of estradiol, estrone, sex hormone binding globulin (SHBG) and beta-endorphin were measured at two- to four-week intervals. RESULTS: Estrogen-androgen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessments. Plasma levels of estradiol and estrone increased significantly in all patients as compared to the postplacebo baseline and decreased in comparison to circulating estrogen concentrations on previous therapy. Relative proportions of free and bound steroid hormone exhibited contrasting shifts during estrogen and estrogen-androgen therapy. SHBG increased in the estrogen group and decreased in the estrogen-androgen group, leading to lower amounts of free androgens during estrogen therapy and increased free androgen levels during estrogen-androgen therapy. Since proportions of free (bioavailable) ovarian steroids would correlate inversely with plasma protein binding capacity, the beneficial effects of oral estrogen-androgen therapy on sexual sensation and desire may be due either to the administered androgen or to the increased availability of endogenous and exogenous androgens, particularly in the central nervous system. CONCLUSION: Sexual desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy. Sexual function improved with estrogen-androgen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy. This leads to the conclusion that androgens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Female_MeSH M_Gonadal_Steroid_Hormones_MeSH S_pharmacology_MeSH Gonadal_Steroid_Hormones_pharmacology_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Libido_MeSH S_drug_effects_MeSH Libido_drug_effects_MeSH M_Methyltestosterone_MeSH S_administration_&_dosage_MeSH Methyltestosterone_administration_&_dosage_MeSH S_pharmacology_MeSH Methyltestosterone_pharmacology_MeSH M_Middle_Aged_MeSH M_Neurosecretory_Systems_MeSH S_drug_effects_MeSH Neurosecretory_Systems_drug_effects_MeSH M_Postmenopause_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH S_pharmacology_MeSH Progestins_pharmacology_MeSH M_Sexual_Behavior_MeSH S_drug_effects_MeSH Sexual_Behavior_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_Congeners_MeSH S_administration_&_dosage_MeSH Testosterone_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Testosterone_Congeners_pharmacology_MeSH 
****** 9840563
----K I
----T Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial.
----A OBJECTIVE: To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. METHODS: This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45-64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. RESULTS: In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17-0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92-2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61-0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62-0.68). CONCLUSION: These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH M_Eating_Disorders_MeSH S_chemically_induced_MeSH Eating_Disorders_chemically_induced_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Headache_MeSH S_chemically_induced_MeSH Headache_chemically_induced_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH M_Mood_Disorders_MeSH S_chemically_induced_MeSH Mood_Disorders_chemically_induced_MeSH M_Neurobehavioral_Manifestations_MeSH S_drug_effects_MeSH Neurobehavioral_Manifestations_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH S_physiopathology_MeSH Vasomotor_System_physiopathology_MeSH M_Weight_Gain_MeSH S_drug_effects_MeSH Weight_Gain_drug_effects_MeSH 
****** 9932566
----K E
----T Continuous combined hormone replacement therapy compared with tibolone.
----A OBJECTIVE: To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day. METHODS: In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test. RESULTS: One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group. CONCLUSION: Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Lipoproteins_MeSH S_blood_MeSH Lipoproteins_blood_MeSH M_Menstruation_MeSH S_drug_effects_MeSH Menstruation_drug_effects_MeSH M_Middle_Aged_MeSH M_Minor_Histocompatibility_Loci_MeSH M_Norethindrone_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Norpregnenes_MeSH S_adverse_effects_MeSH Norpregnenes_adverse_effects_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Progesterone_Congeners_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10072236
----K E
----T Effect of acute testosterone on myocardial ischemia in men with coronary artery disease.
----A The effect of acute testosterone administration on exercise-induced myocardial ischemia was assessed in 14 men with coronary artery disease and low plasma testosterone concentrations in a study of randomized, double-blind, crossover design. Testosterone increased time to 1-mm ST-segment depression compared with placebo by 66 (15 to 117) seconds (p = 0.016), suggesting a beneficial effect of testosterone on myocardial ischemia in these patients.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Comparative_Study_MeSH M_Coronary_Angiography_MeSH M_Coronary_Arteriosclerosis_MeSH S_blood_MeSH Coronary_Arteriosclerosis_blood_MeSH S_drug_therapy_MeSH Coronary_Arteriosclerosis_drug_therapy_MeSH S_radiography_MeSH Coronary_Arteriosclerosis_radiography_MeSH M_Double-Blind_Method_MeSH M_Electrocardiography_MeSH S_drug_effects_MeSH Electrocardiography_drug_effects_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Exercise_Test_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Injections__Intravenous_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_blood_MeSH Myocardial_Ischemia_blood_MeSH S_diagnosis_MeSH Myocardial_Ischemia_diagnosis_MeSH S_drug_therapy_MeSH Myocardial_Ischemia_drug_therapy_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_blood_MeSH Testosterone_blood_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 10090424
----K E
----T Oral micronized progesterone.
----A This review sought to examine the rationale for selecting an oral micronized progesterone formulation rather than a synthetic progestin for some of the main indications for progestogens. Unopposed estrogen use is associated with a high risk (relative risk, 2.1 to 5.7) of endometrial hyperplasia and adenocarcinoma, and it has been understood for some time that a progestogen must be added for at least 10 to 14 days per month to prevent these effects. However, the most commonly used synthetic progestins, norethisterone and medroxyprogesterone acetate, have been associated with metabolic and vascular side effects (eg, suppression of the vasodilating effect of estrogens) in both experimental and human controlled studies. All comparative studies to date conclude that the side effects of synthetic progestins can be minimized or eliminated through the use of natural progesterone, which is identical to the steroid produced by the corpus luteum. The inconvenience associated with the use of injectable, rectal, or vaginal formulations of natural progesterone can be circumvented by using orally administered micronized progesterone. The bioavailability of micronized progesterone is similar to that of other natural steroids, and interindividual and intraindividual variability of area under the curve is similar to that seen with synthetic progestins. A clear dose-ranging effect has been demonstrated, and long-term protection of the endometrium has been established. Micronized progesterone has been used widely in Europe since 1980 at dosages ranging from 300 mg/d (taken at bedtime) 10 days a month for women wishing regular monthly bleeding to 200 mg 14 days a month or 100 mg 25 days a month for women willing to remain amenorrheic. This therapy is well tolerated, with the only specific side effect being mild and transient drowsiness, an effect minimized by taking the drug at bedtime. The prospective, comparative Postmenopausal Estrogens/Progestin Intervention trial has recommended oral micronized progesterone as the first choice for opposing estrogen therapy in nonhysterectomized postmenopausal women.
----P Journal_Article Review Review__Academic 
----M M_Administration__Oral_MeSH M_Animals_MeSH M_Chemistry__Pharmaceutical_MeSH M_Clinical_Trials_MeSH M_Evaluation_Studies_MeSH M_Female_MeSH M_Human_MeSH M_Postmenopause_MeSH M_Premenopause_MeSH P_Progesterone_MeSH S_pharmacokinetics_MeSH Progesterone_pharmacokinetics_MeSH S_pharmacology_MeSH Progesterone_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH P_Progesterone_Congeners_MeSH S_pharmacokinetics_MeSH Progesterone_Congeners_pharmacokinetics_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10091204
----K E
----T HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.
----A OBJECTIVES: We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial. METHODS: A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13,100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth years); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. RESULTS: Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). CONCLUSIONS: This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH M_Female_MeSH M_Fractures_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_Vitamin_D_MeSH S_therapeutic_use_MeSH Vitamin_D_therapeutic_use_MeSH 
****** 10212006
----K E
----T Premenstrual symptoms in women with premenstrual asthma.
----A STUDY OBJECTIVES: To characterize and compare premenstrual symptoms (mood, physical) throughout two menstrual cycles with and without estradiol administration, in women with premenstrual asthma (PMA), and to examine relationships between asthma symptoms versus premenstrual symptoms and pulmonary function versus premenstrual symptoms in these women. DESIGN: Open-label, longitudinal, 9-week study (consisting of two complete menstrual cycles). SETTING: Clinical study at the University of Kentucky; data analysis at the University of British Columbia and Children's and Women's Health Centre of British Columbia. PATIENTS: Fourteen women (age 35.6 +/- 6.6 yrs) with mild to moderate asthma with a baseline ratio of forced expiratory volume in 1 second:forced vital capacity of 0.72 +/- 0.12. INTERVENTIONS: Women were followed for two complete menstrual cycles. During the second complete cycle (i.e., cycle 3), they received estradiol 2 mg orally between days 23 and 28 (premenstrual). MEASUREMENTS AND MAIN RESULTS: Throughout both cycles 2 and 3, each subject recorded premenstrual symptom questionnaire scores (15 mood and physical symptoms, graded 0-3) every morning on awakening. Peak expiratory flow rate (PEFR) and visual analog scales of asthma symptoms (cough, wheezing, breathlessness, chest tightness) were recorded daily at the same time. Seven subjects showed a classic pattern of premenstrual symptoms. Four of the five subjects who complained of PMA symptoms at study enrollment also demonstrated this classic pattern of premenstrual symptoms. After estradiol administration, four women had lower symptom scores, eight had higher scores, and two had the same scores. Overall, estradiol had no significant effect on symptoms (mean area under the curve 18.9 +/- 14.8 day(-1) vs 20.3 +/- 14.8 day(-1), p>0.05). Ten subjects had significant relationships between asthma symptoms and premenstrual symptoms, whereas six had significant relationships between PEFR and premenstrual symptoms. CONCLUSIONS: Exogenous estradiol administration had no significant effect on premenstrual symptoms in women with PMA. The lack of a significant effect allows for patient blinding in a placebo-controlled, crossover study of exogenous estradiol in PMA that is currently under way Clinical implications of relationships between asthma symptoms versus premenstrual symptoms and pulmonary function versus premenstrual symptoms may warrant further study.
----P Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Affect_MeSH S_physiology_MeSH Affect_physiology_MeSH M_Area_Under_Curve_MeSH M_Asthma_MeSH S_drug_therapy_MeSH Asthma_drug_therapy_MeSH S_etiology_MeSH Asthma_etiology_MeSH S_physiopathology_MeSH Asthma_physiopathology_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_pharmacokinetics_MeSH Estradiol_pharmacokinetics_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Lung_MeSH S_physiopathology_MeSH Lung_physiopathology_MeSH M_Menstrual_Cycle_MeSH S_drug_effects_MeSH Menstrual_Cycle_drug_effects_MeSH S_physiology_MeSH Menstrual_Cycle_physiology_MeSH M_Premenstrual_Syndrome_MeSH S_drug_therapy_MeSH Premenstrual_Syndrome_drug_therapy_MeSH S_physiopathology_MeSH Premenstrual_Syndrome_physiopathology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10227004
----K E
----T Postmenopausal women without previous or current vasomotor symptoms do not flush after abruptly abandoning estrogen replacement therapy.
----A BACKGROUND: Most but not all women suffer from vasomotor symptoms around menopause. The exact mechanisms behind these symptoms are unknown, but the rate of decline in estrogen concentrations has been suggested to affect the risk of hot flushes. OBJECTIVE: The objective was to assess whether vasomotor symptoms were induced in women without previous such symptoms, when the women were given combined estradiol and progestagen therapy for 3 months, whereafter therapy was abruptly withdrawn. MATERIALS AND METHOD: After randomization, 40 postmenopausal women without previous or current vasomotor symptoms were treated transdermally with either 50 micrograms/day 17 beta-estradiol or placebo during 14 weeks. During the 13th and 14th weeks, treatment was combined with oral medroxyprogesterone acetate 10 mg/day. Serum estradiol and follicle-stimulating hormone (FSH) concentrations were analysed before and after 12 weeks of therapy. Climacteric symptoms were assessed at the same intervals as well as 8 weeks after the end of therapy. RESULTS: All women had low pretreatment levels of estradiol and high FSH concentrations. During estradiol therapy estradiol levels increased significantly, whereas FSH only decreased slightly. No woman developed vasomotor symptoms after withdrawal of therapy. CONCLUSION: Postmenopausal women without previous or current vasomotor symptoms did not develop such symptoms when estrogen replacement therapy was first instituted and then abruptly stopped. Probably other factors than the rate with which estrogen concentrations decrease determine whether or not a woman will develop vasomotor symptoms. Evidently, estrogens can be prescribed to a woman who has no vasomotor symptoms, without much risk of inducing such symptoms if she decides to abandon therapy, even after 3 months of treatment.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hot_Flashes_MeSH S_metabolism_MeSH Hot_Flashes_metabolism_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH M_Menstruation-Inducing_Agents_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10375338
----K I
----T The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.
----A BACKGROUND: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women. OBJECTIVE: To determine the bone-sparing effect of continuous low-dose HRT in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University osteoporosis research and clinical center. PATIENTS: 128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less. INTERVENTION: Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups. MEASUREMENTS: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months. RESULTS: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived. CONCLUSIONS: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Analysis_of_Variance_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH S_urine_MeSH Biological_Markers_urine_MeSH M_Bone_Density_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH M_Creatinine_MeSH S_urine_MeSH Creatinine_urine_MeSH P_Dietary_Supplements_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Hydroxyproline_MeSH S_urine_MeSH Hydroxyproline_urine_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_adverse_effects_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Vitamin_D_MeSH S_administration_&_dosage_MeSH Vitamin_D_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Vitamin_D_analogs_&_derivatives_MeSH 
****** 10372727
----K E
----T Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.
----A The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Androstenedione_MeSH S_blood_MeSH Androstenedione_blood_MeSH M_Antibody_Specificity_MeSH M_Biotransformation_MeSH M_Cross-Over_Studies_MeSH M_Dehydroepiandrosterone_MeSH S_pharmacokinetics_MeSH Dehydroepiandrosterone_pharmacokinetics_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_blood_MeSH Dehydroepiandrosterone_Sulfate_blood_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogens_MeSH S_blood_MeSH Estrogens_blood_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Radioimmunoassay_MeSH 
****** 10399774
----K E
----T Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study.
----A Preliminary evidence from clinical studies indicates that treatment with estrogen augments cognitive function for women with Alzheimer's disease (AD). The neurobiology of estrogen, particularly its neuromodulatory and neuroprotective actions, provide a viable basis to support such cognition-enhancing effects. We conducted a placebo-controlled, double-blind, parallel-group design pilot clinical study to evaluate the cognitive and neuroendocrine response to estrogen administration for postmenopausal women with AD. Twelve women with probably AD of mild-moderate severity completed the study. During an eight week treatment period, six women received 0.05 mg/day dosage of 17 beta-estradiol via a skin patch and the remaining six wore a placebo skin patch. Subjects were randomized to equal distribution, and evaluated at baseline, at weeks 1, 3, 5, and 8 on treatment, and at weeks 9, 10, 11, and 13 off treatment. On each day of evaluation, cognition was assessed using a battery of neuropsychological tests, and blood samples were collected to measure plasma concentrations of estradiol and estrone. In addition, several neuroendocrine markers were measured in plasma to evaluate the relationship between estrogen-induced cognitive effects and fluctuations in the catecholaminergic and insulin-like growth factor systems. Significant effects of estrogen treatment were observed on attention (i.e. Stroop: number of self-corrections in the Interference condition, F[1,8] = 8.22, P < 0.03) and verbal memory (i.e., Buschke: delayed cued recall, F[3,30] = 4.31, P < 0.02). The salutary effects of estrogen on cognition were observed after the first week of treatment, and started to diminish when treatment was terminated. For women treated with estrogen, enhancement in verbal memory was positively correlated with plasma levels of estradiol (r = 0.96, P < 0.02) and negatively correlated with concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) in plasma (r = -0.92, P < 0.03). Furthermore, a trend in the data was evident to suggest a negative relationship between plasma levels of insulin-like growth factor-1 (IGF-1) and verbal memory (r = -0.86, P = 0.06). Estrogen administration suppressed peripheral markers of the IGF system, as evidenced by a negative correlation between plasma concentration of estradiol and IGF-1 (r = -0.93, P < 0.03), and a trend for a similar relationship between plasma levels of estradiol and IGFBP-3 (r = -0.86, P = 0.06). With respect to the catecholamines assayed, norepinephrine was positively correlated with verbal memory (r = 0.95, P < 0.02) for women who were treated with estrogen. Furthermore, there was a trend to suggest a negative relationship between plasma epinephrine levels and the number of errors committed on a test of attention (r = -0.84, P = 0.07). In the placebo group, no significant effects of estrogen replacement were evident either on measures of cognition or on any of the neuroendocrine markers. The results of this study suggest that estrogen replacement may enhance cognition for postmenopausal women with AD. Furthermore, several markers of neuroendocrine activity may serve to index the magnitude of estrogen-induced facilitation on cognition. In addition, research findings from the present study will provide important information for the design of larger prospective clinical studies that are essential to definitively establish the therapeutic role of estrogen replacement for postmenopausal women with AD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alzheimer_Disease_MeSH S_blood_MeSH Alzheimer_Disease_blood_MeSH S_drug_therapy_MeSH Alzheimer_Disease_drug_therapy_MeSH S_psychology_MeSH Alzheimer_Disease_psychology_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_Binding_Protein_3_MeSH S_blood_MeSH Insulin-Like_Growth_Factor_Binding_Protein_3_blood_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_I_metabolism_MeSH M_Mental_Recall_MeSH S_drug_effects_MeSH Mental_Recall_drug_effects_MeSH P_Neuropsychological_Tests_MeSH M_Norepinephrine_MeSH S_blood_MeSH Norepinephrine_blood_MeSH M_Pilot_Projects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH 
****** 10408073
----K E
----T [The effects of hormone replacement therapy on ovarian function in premenopausal women after hysterectomy]
----A OBJECTIVE: Examining the consequences of temporary postoperative hormone replacement therapy following hysterectomy for the function of the ovaries and the subjective well-being of women. MATERIAL AND METHODS: Hormone profiles (Estradiol, FSH, LH, Testosterone, DHEA) and typical estradiol deficiency phenomena were investigated prospectively in premenopausal hysterectomized women with intact ovaries. Group 1 (n = 21) was replaced transdermally following surgery for 3 weeks with estradiol patch 0.05 mg daily. Group 2 (n = 21) got no hormones. RESULTS: Group 1 had a remarkable decrease of estradiol after 10 days to 59% and after 6 weeks to 71% of the starting point. Gonadotropins showed an increase in this group. In group 2 without replacement there was only a small decrease of estradiol after 10 days and after 6 weeks the level was higher than before hysterectomy. Testosterone also decreased in group 1 to 64% of the level before surgery after 6 weeks, whereas in the comparing group it was 87%. On the other hand in group 1 only 2 of 21 women, but 10 of 21 in group 2 showed climacteric-like symptoms. CONCLUSIONS: HRT over 3 weeks induces ovarian suppression, which is still seen 6 weeks after hysterectomy. But hormonally treated women have clearly less subjective complaints.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Comparative_Study_MeSH M_Dehydroepiandrosterone_MeSH S_blood_MeSH Dehydroepiandrosterone_blood_MeSH M_Dyspareunia_MeSH S_etiology_MeSH Dyspareunia_etiology_MeSH S_prevention_&_control_MeSH Dyspareunia_prevention_&_control_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hot_Flashes_MeSH S_etiology_MeSH Hot_Flashes_etiology_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH P_Hysterectomy_MeSH S_adverse_effects_MeSH Hysterectomy_adverse_effects_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Middle_Aged_MeSH M_Ovary_MeSH S_drug_effects_MeSH Ovary_drug_effects_MeSH S_physiopathology_MeSH Ovary_physiopathology_MeSH M_Patient_Satisfaction_MeSH P_Postoperative_Care_MeSH M_Premenopause_MeSH M_Prospective_Studies_MeSH M_Sleep_Disorders_MeSH S_etiology_MeSH Sleep_Disorders_etiology_MeSH S_prevention_&_control_MeSH Sleep_Disorders_prevention_&_control_MeSH M_Statistics__Nonparametric_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 10430010
----K E
----T Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group.
----A Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone deficiency. The efficacy, safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials. In an open-label comparative trial a total of 219 postmenopausal women were randomized to the estradiol-releasing vaginal ring or to estriol suppositories. In terms of efficacy both treatment arms were shown to be equivalent; however, significantly higher rates of acceptability were found for the vaginal ring. In a double-blinded placebo-controlled study a total of 84 patients were randomized to either treatment arm for a period of 24 weeks. The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Atrophy_MeSH M_Double-Blind_Method_MeSH M_Drug_Delivery_Systems_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH P_Pessaries_MeSH M_Treatment_Outcome_MeSH M_Urogenital_Diseases_MeSH S_drug_therapy_MeSH Urogenital_Diseases_drug_therapy_MeSH S_pathology_MeSH Urogenital_Diseases_pathology_MeSH 
****** 10434233
----K E
----T Comparison of the pharmacokinetics of 17 beta-estradiol after a single 4-day application of Oesclim 50, Oesclim 100, and Vivelle 0.05 (Menorest 50) transdermal delivery systems.
----A Oesclim (Laboratoires Fournier, Dijon, France), also known as Esclim or Esclima, is a new estradiol transdermal delivery system (TDS) developed for the treatment of menopausal vasomotor symptoms. This open, randomized, three-way crossover study compared in 24 healthy postmenopausal women the pharmacokinetics of estradiol after a single 4-day application of Oesclim 50, Oesclim 100, and Vivelle 0.05 (CibaGeneva Pharmaceuticals, Summit, NJ; known as Menorest 50 in Europe, Rhone-Poulenc Rorer) on the upper buttock. Serum estradiol concentrations were determined by a validated radioimmunoassay method from samples taken before and during each TDS application. The concentration-time profiles for Vivelle 0.05 and Oesclim 50 were comparable with a similar absorption rate, giving a maximum concentration (Cmax) of 49 and 53 pg/mL above baseline, respectively, followed by a plateau throughout the 96-hour application period. At the end of this period, mean corrected estradiol concentrations were 18 and 19 pg/mL, respectively. The estradiol serum concentrations obtained after an application of Oesclim 100 were approximately twice as high than with Oesclim 50. All products were well tolerated, but skin intolerance was more frequent with Vivelle 0.05 (4 patients; four reports) and Oesclim 100 (3 patients; three reports) than with Oesclim 50 (none). Problems of imperfect adhesion were more than five times as frequent with Vivelle 0.05 (44%) than with Oesclim (8%).
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Area_Under_Curve_MeSH M_Asthenia_MeSH S_chemically_induced_MeSH Asthenia_chemically_induced_MeSH M_Comparative_Study_MeSH M_Cross-Over_Studies_MeSH P_Drug_Delivery_Systems_MeSH M_Erythema_MeSH S_chemically_induced_MeSH Erythema_chemically_induced_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_pharmacokinetics_MeSH Estradiol_pharmacokinetics_MeSH M_Female_MeSH M_Headache_MeSH S_chemically_induced_MeSH Headache_chemically_induced_MeSH M_Human_MeSH M_Menorrhagia_MeSH S_chemically_induced_MeSH Menorrhagia_chemically_induced_MeSH M_Middle_Aged_MeSH M_Pain_MeSH S_chemically_induced_MeSH Pain_chemically_induced_MeSH M_Skin_MeSH S_drug_effects_MeSH Skin_drug_effects_MeSH S_pathology_MeSH Skin_pathology_MeSH M_Time_Factors_MeSH 
****** 10451908
----K E
----T Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels.
----A The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Aged_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Mental_Recall_MeSH S_drug_effects_MeSH Mental_Recall_drug_effects_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH 
****** 10472853
----K E
----T Uterine bleeding in postmenopausal women on continuous therapy with estradiol and norethindrone acetate. Endometrium Study Group.
----A OBJECTIVE: To investigate the incidence of uterine bleeding during 12 months of treatment with 17beta-estradiol (E2) 1 mg, unopposed or in combination with three doses of norethindrone acetate. METHODS: This study was a prospective, double-masked, randomized, multicenter trial. A total of 1176 healthy postmenopausal women age 45 years and older without evidence of endometrial abnormalities were randomly assigned to receive either unopposed E2 1 mg, or continuous-combined formulations of E2 1 mg and norethindrone acetate 0.1 mg, 0.25 mg, or 0.5 mg. Any spotting or bleeding episodes during the treatment period were recorded in a daily diary and reported by weekly telephone calls. RESULTS: The incidence of bleeding was low in the combination groups, even during the initial 3 months of treatment (24-28%), after which it decreased with increasing doses of norethindrone acetate. Conversely, the incidence of bleeding increased over time with unopposed E2 1 mg. After the initial 3 months, the incidence of bleeding among the combination groups was lowest in the norethindrone acetate 0.5 mg group. Among women initiating therapy close to menopause, fewer reported bleeding with norethindrone acetate 0.5 mg than with the other combination groups. There was a significantly (P<.05) lower discontinuation rate due to bleeding in the norethindrone acetate 0.5 mg group compared with all other treatment groups. CONCLUSION: Continuous-combined formulations of E2 1 mg with norethindrone acetate 0.1, 0.25, or 0.5 mg are associated with a low incidence of uterine bleeding. After the initial 3 months of treatment, bleeding profiles improved with increasing doses of norethindrone acetate.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Incidence_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH S_epidemiology_MeSH Uterine_Hemorrhage_epidemiology_MeSH 
****** 10484532
----K E
----T Novel inflammatory markers of coronary risk: theory versus practice.
----A 
----P Comment Editorial 
----M M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH M_C-Reactive_Protein_MeSH S_analysis_MeSH C-Reactive_Protein_analysis_MeSH M_Coronary_Disease_MeSH S_blood_MeSH Coronary_Disease_blood_MeSH M_Cytokines_MeSH S_blood_MeSH Cytokines_blood_MeSH M_Human_MeSH 
****** 10487657
----K I
----T Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomized study.
----A Sodium fluoride stimulates bone formation and has been used to treat osteoporosis for decades despite debate about the antifracture efficacy. Hormone replacement therapy (HRT) results in only modest increases in bone mineral density (BMD). However, for women with low bone mass, the ideal therapy should not only inhibit bone resorption but simultaneously stimulate bone formation to increase bone mass above the fracture threshold. We thus performed a randomized, double-blind, placebo-controlled intervention study to prospectively investigate the effect of a low dose of fluoride, in combination with HRT, on BMD and biochemical markers of bone turnover. One hundred healthy postmenopausal women (60-70 yr old) were thus randomly assigned to: 1) HRT [transdermal 17beta-estradiol, releasing 50 microg/day; plus oral norethisterone acetate (NETA), 1 mg/day]; or 2) oral monofluorophosphate (MFP; equivalent to fluoride, 20 mg/day); or 3) HRT+MFP; or 4) placebo, for 96 weeks. All participants received a calcium supplement of 1000 mg/day. Sixty-eight women completed the study. We found a pronounced, linear increase in spinal BMD during treatment with HRT+MFP [11.8% (1.7% SEM)], which was significantly greater than the increase in the HRT group [4.0% (0.5% per yr); P < 0.05]. MFP produced a smaller increase [2.4% (0.6% per yr)], whereas there was no change in the placebo group [0.0% (0.5% SEM)]. Similar changes were found at the other skeletal sites (distal forearm, hip, and total body). Markers of bone formation showed a fall in the HRT group, which was significantly more pronounced than in the combined HRT+MFP group. A nonsignificant increase was found in the MFP group, whereas the placebo group showed a decrease caused by calcium treatment. The marker of bone resorption decreased significantly more in the HRT and the HRT+MFP groups than in the placebo group but tended to increase in the MFP group. In conclusion, this study shows, by use of biochemical markers of bone turnover, that bone resorption and formation may be dissociated, as a result of actions of two compounds with diverging effects on bone turnover. Furthermore, the synergistic effects of relatively low doses of the compounds suggested statistically and clinically significant increases in trabecular and probably also cortical bone. Adverse effects were relatively rare and mild.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH P_Bone_Resorption_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH M_Double-Blind_Method_MeSH M_Drug_Synergism_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Fluorides_MeSH S_administration_&_dosage_MeSH Fluorides_administration_&_dosage_MeSH S_adverse_effects_MeSH Fluorides_adverse_effects_MeSH S_therapeutic_use_MeSH Fluorides_therapeutic_use_MeSH M_Human_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH M_Phosphates_MeSH S_administration_&_dosage_MeSH Phosphates_administration_&_dosage_MeSH S_adverse_effects_MeSH Phosphates_adverse_effects_MeSH S_therapeutic_use_MeSH Phosphates_therapeutic_use_MeSH M_Placebos_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 10486788
----K E
----T Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study.
----A OBJECTIVE: The incidence of sleep apnea syndrome (SAS) in women increases after menopause. Progestins alone do not alleviate SAS in menopausal women. However, progestins may require concomitant estrogen administration and estrogen alone may stimulate breathing during sleep. To test these hypotheses, we studied the effects of estrogen alone and estrogen combined with progestin on SAS in menopausal women, using a prospective, cross-over, inception cohort study. DESIGN: In this pilot study, five women who developed SAS after menopause underwent 2 nights of polysomnography to obtain a baseline, then returned for polysomnography after 3-4 weeks of taking micronized 17 beta-estradiol (E2) and after 10-12 days of taking E2 combined with medroxyprogesterone acetate (E2 + P). Sleep stages were scored according to Rechtshaffen and Kales, frequency and length of apneas were recorded for each subject each night, and the data were analyzed by Student's t test. RESULTS: E2 and E2 + P both reduced the Respiratory Distress Index. E2 also raised the lowest oxygen desaturation associated with apneic episodes. Total minutes of rapid eye movement sleep increased, and the number of waking episodes decreased when the women were taking E2 and E2 + P, as previously reported. CONCLUSIONS: Within 1 month after initiating E2 or E2 + P, SAS was reduced in all patients. The Respiratory Distress Index decreased by 25%, and the addition of progestin brought the SAS reduction to 50% in this pilot study. A randomized study in a large group of patients is justified by the findings of this study. Because SAS increases the risk of cardiovascular disease and fatal accidents, the amelioration of SAS by sex steroid hormones could have significant implications for the health of menopausal women.
----P Clinical_Trial Journal_Article 
----M M_Aged_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Medroxyprogesterone_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_therapeutic_use_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Pilot_Projects_MeSH M_Polysomnography_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Sleep_Apnea_Syndromes_MeSH S_diagnosis_MeSH Sleep_Apnea_Syndromes_diagnosis_MeSH S_drug_therapy_MeSH Sleep_Apnea_Syndromes_drug_therapy_MeSH S_etiology_MeSH Sleep_Apnea_Syndromes_etiology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Treatment_Outcome_MeSH 
****** 10486791
----K E
----T Liver function in postmenopausal women on estrogen-androgen hormone replacement therapy: a meta-analysis of eight clinical trials.
----A OBJECTIVE: To compare hepatic biochemical changes of a combined estrogen-androgen preparation with that of estrogen alone in postmenopausal women. DESIGN: Hepatic biochemical values from 511 surgical and 130 nonsurgically menopausal women being treated with hormone replacement therapy were pooled from eight similarly designed studies performed between March 1988 and January 1996 comparing esterified estrogen-methyl-testosterone preparations with esterified estrogen, conjugated equine estrogens, and placebo controls. The eight studies in this meta-analysis were controlled, randomized, multicenter, double-blind with identical or similar treatment arms. For hepatic biochemistry parameters, raw data summaries and mean changes from baseline values with standard error (SE) were evaluated for the dosages and treatment groups at various time periods throughout the studies. RESULTS: Eight controlled trials involving 641 surgically and nonsurgically menopausal women were included. Changes from the pretreatment baseline values of liver function were compared at 1, 3, 6, 12, 18, and 24 months of therapy. No patients demonstrated hepatotoxicity or clinically significant elevation of liver biochemistry values. None of the liver biochemistry changes measured in these studies were of clinical significance, nor were there biochemical differences between estrogen therapy alone compared with combined esterified estrogen-methyltestosterone preparation when administered to postmenopausal women during a period of up to 24 months. CONCLUSIONS: Combined esterified estrogen-methyltestosterone therapy (in doses of 0.625 mg esterified estrogen + 1.25 mg methyltestosterone or 1.25 mg esterified estrogen + 2.5 mg methyltestosterone) was found to be safe regarding hepatic function in postmenopausal women during the course of 24 months in eight controlled clinical trials.
----P Journal_Article Meta-Analysis 
----M M_Aged_MeSH M_Androgens_MeSH S_administration_&_dosage_MeSH Androgens_administration_&_dosage_MeSH S_adverse_effects_MeSH Androgens_adverse_effects_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Liver_MeSH S_drug_effects_MeSH Liver_drug_effects_MeSH S_pathology_MeSH Liver_pathology_MeSH M_Liver_Function_Tests_MeSH M_Middle_Aged_MeSH M_Multicenter_Studies_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Randomized_Controlled_Trials_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 10505587
----K E
----T Effects of triazolam at three phases of the menstrual cycle.
----A This study investigated the subjective and behavioral effects of a commonly used benzodiazepine, triazolam, in healthy women at three phases of the menstrual cycle: follicular, periovulatory, and luteal. Ovarian hormones or their metabolites have direct and indirect actions on neuronal receptors, which may affect responses to psychoactive drugs acting on the same central nervous system receptors. This study explored the effect of menstrual cycle phase on the mood-altering and performance effects of a single oral dose of the benzodiazepine triazolam. Twenty women received triazolam (0.25 mg orally) or placebo at the follicular, periovulatory, and luteal phases of their menstrual cycles in a within-subject design. Dependent measures included self-reported mood states, psychomotor performance, and plasma levels of triazolam, estradiol, progesterone, and allopregnanolone. After administration of triazolam, most subjects reported the expected increases in fatigue and decreases in arousal and psychomotor performance. Neither plasma levels nor mood and performance effects of triazolam differed across the three phases. This study illustrates a useful methodology for assessing responses to psychoactive drugs in normally cycling women and shows that the effects of this drug were highly stable across the cycle.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Area_Under_Curve_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Fatigue_MeSH S_chemically_induced_MeSH Fatigue_chemically_induced_MeSH M_Female_MeSH M_GABA_Modulators_MeSH S_adverse_effects_MeSH GABA_Modulators_adverse_effects_MeSH S_pharmacokinetics_MeSH GABA_Modulators_pharmacokinetics_MeSH S_pharmacology_MeSH GABA_Modulators_pharmacology_MeSH M_Half-Life_MeSH M_Human_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Menstrual_Cycle_MeSH S_metabolism_MeSH Menstrual_Cycle_metabolism_MeSH M_Progesterone_MeSH S_blood_MeSH Progesterone_blood_MeSH M_Psychomotor_Performance_MeSH S_drug_effects_MeSH Psychomotor_Performance_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Triazolam_MeSH S_adverse_effects_MeSH Triazolam_adverse_effects_MeSH S_pharmacokinetics_MeSH Triazolam_pharmacokinetics_MeSH S_pharmacology_MeSH Triazolam_pharmacology_MeSH 
****** 10522982
----K E
----T Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men.
----A The pharmacokinetics, efficacy, and safety of the Androderm testosterone (T) transdermal system (TTD) and intramuscular T enanthate injections (i.m.) for the treatment of male hypogonadism were compared in a 24-week multicenter, randomized, parallel-group study. Sixty-six adult hypogonadal men (22-65 years of age) were withdrawn from prior i.m. treatment for 4-6 weeks and then randomly assigned to treatment with TTD (two 2.5-mg systems applied nightly) or i.m. (200 mg injected every 2 weeks); there were 33 patients per group. Twenty-six patients in the TTD group and 32 in the i.m. group completed the study. TTD treatment produced circadian variations in the levels of total T, bioavailable T, dihydrotestosterone, and estradiol within the normal physiological ranges. i.m. treatment produced supraphysiological levels of T, bioavailable T, and estradiol (but not dihydrotestosterone) for several days after each injection. Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients (range, 77-100%) than i.m. patients (range, 19-84%). Both treatments normalized LH levels in approximately 50% of patients with primary hypogonadism; however, LH levels were suppressed to the subnormal range in 31% of i.m. patients vs. 0% of TTD patients. Both treatments maintained sexual function (assessed by questionnaire and Rigiscan) and mood (Beck Depression Inventory) at the prior treatment levels. Prostate-specific antigen levels, prostate volumes, and lipid and serum chemistry parameters were comparable in both treatment groups. Transient skin irritation from the patches was reported by 60% of the TTD patients, but caused only three patients (9%) to discontinue treatment. i.m. treatment produced local reactions in 33% of patients and was associated with significantly more abnormal hematocrit elevations (43.8% of patients) compared with TTD treatment (15.4% of patients). Gynecomastia resolved more frequently during TTD treatment (4 of 10 patients) than with i.m. treatment (1 of 9 patients). Although both treatments seem to be efficacious for replacing T in hypogonadal men, the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over i.m. in minimizing excessive stimulation of erythropoiesis, preventing/ameliorating gynecomastia, and not over-suppressing gonadotropins.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Comparative_Study_MeSH M_Drug_Administration_Schedule_MeSH M_Hematocrit_MeSH M_Human_MeSH M_Hypogonadism_MeSH S_blood_MeSH Hypogonadism_blood_MeSH S_drug_therapy_MeSH Hypogonadism_drug_therapy_MeSH S_pathology_MeSH Hypogonadism_pathology_MeSH M_Injections__Intramuscular_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Permeability_MeSH M_Prostate_MeSH S_drug_effects_MeSH Prostate_drug_effects_MeSH S_pathology_MeSH Prostate_pathology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Testosterone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Testosterone_analogs_&_derivatives_MeSH S_pharmacokinetics_MeSH Testosterone_pharmacokinetics_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 12065927
----K E
----T Novel treatment of delayed male puberty with aromatase inhibitors.
----A BACKGROUND: As the evidence for the role of oestrogens in epiphyseal closure appears unequivocal, we hypothesized that boys with constitutional delay of puberty would attain greater adult height if oestrogen action was suppressed. METHODS: We conducted a randomized, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone plus placebo or testosterone plus a potent fourth-generation aromatase inhibitor, letrozole. FINDINGS: Letrozole effectively inhibited oestrogen synthesis. The 17beta-oestradiol concentrations increased in the untreated group and in the testosterone/placebo-treated group, but in the testosterone/letrozole-treated group no such increase was observed until letrozole treatment was discontinued. Testosterone concentrations were threefold higher in the testosterone/letrozole-treated group than in the other groups. Within 18 months, bone age had advanced by 1.1 +/- 0.3 years in the untreated group and by 1.7 +/- 0.3 years in the testosterone/placebo-treated group, but only by 0.9 +/- 0.2 years in the testosterone/letrozole-treated group (p = 0.02 between treatment groups). Predicted adult height did not change significantly in the untreated group and in the testosterone/placebo-treated group, whereas in the testosterone/letrozole-treated group the increase was 5.1 +/- 1.2 cm (p = 0.004). CONCLUSIONS: Our findings suggest that, if oestrogen action is inhibited in growing adolescents, adult height will increase. This observation provides a rationale for studies aimed at delaying bone maturation in several growth disorders.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Analysis_of_Variance_MeSH M_Aromatase_MeSH S_antagonists_&_inhibitors_MeSH Aromatase_antagonists_&_inhibitors_MeSH M_Biological_Markers_MeSH S_blood_MeSH Biological_Markers_blood_MeSH M_Body_Height_MeSH S_drug_effects_MeSH Body_Height_drug_effects_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Development_MeSH S_drug_effects_MeSH Bone_Development_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Enzyme_Inhibitors_MeSH S_therapeutic_use_MeSH Enzyme_Inhibitors_therapeutic_use_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Growth_MeSH S_drug_effects_MeSH Growth_drug_effects_MeSH M_Human_MeSH M_Male_MeSH M_Nitriles_MeSH S_therapeutic_use_MeSH Nitriles_therapeutic_use_MeSH M_Predictive_Value_of_Tests_MeSH M_Puberty__Delayed_MeSH S_drug_therapy_MeSH Puberty__Delayed_drug_therapy_MeSH M_Testosterone_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH M_Triazoles_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12110412
----K E
----T Relation of sex hormones to bone mineral density in middle-aged men during a 4 year exercise intervention trial.
----A Recent studies have emphasized the symbiotic role of estradiol and testosterone on bone metabolism. Several anthropomorphic-, lifestyle-, and dual-energy X-ray (DXA)-derived parameters were measured with respect to estradiol (E(2)), testosterone (T), free T (fT), and sex hormone-binding globulin (SHBG) in 140 men (aged 53-62 years) participating in a controlled, randomized exercise intervention trial. After 4 years of intervention, 132 (94.3%) men remained as participants. During the period of study, aerobic threshold increased significantly in the exercise intervention group compared with the reference group (13.4% vs. -1.9%: p < 0.023). Serum E(2) and fT were not convincingly related to bone mineral density (BMD) or BMD change. Aerobic threshold or the change in aerobic threshold were not associated with sex hormone or SHBG levels. Body mass index was a significant determinant of T (beta = -0.337), fT (beta = -0.293), and SHBG (beta = -0.306), and smoking predicted T (beta = 0.231) and fT (beta = 0.245). Alcohol intake was a significant determinant of E(2) (beta = 0.213). Ultimately there was no convincing relation between sex hormone levels and BMD or BMD change in middle-aged men.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Chi-Square_Distribution_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Gonadal_Steroid_Hormones_MeSH S_blood_MeSH Gonadal_Steroid_Hormones_blood_MeSH S_physiology_MeSH Gonadal_Steroid_Hormones_physiology_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Multivariate_Analysis_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12110425
----K I
----T Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women.
----A The purpose of this intervention trial was to determine whether changes in bone mass distribution could be observed in postmenopausal women following hormone replacement therapy (HRT) and/or high-impact physical exercise. Eighty healthy women, aged 50-57 years, at <5 years after the onset of menopause and with no previous use of HRT, were randomly assigned to one of four groups: HRT; exercise (Ex); HRT + Ex (ExHRT); and control (Co). HRT administration was conducted in a double-blind manner for 1 year using estradiol plus noretisterone acetate (Kliogest). The exercise groups participated in a 1 year progressive training program consisting of jumping and bounding activities. Subjects participated in two supervised sessions per week and were asked to perform a series of exercises at home 4 days/week. Bone measurements using a quantitative computed tomography scanner (Somatom DR, Siemens) were obtained from the proximal femur, midfemur, proximal tibia, and tibial shaft. Data were analyzed with a software program (BONALYSE 1.3) calculating density (g/cm(3)), cross-sectional area (CSA; mm(2)), and moments of inertia (I(max), I(min), I(polar)). In addition, the bone mass spectrum was determined as a function of the angular distribution around the bone mass center (polar distribution) and the distance from the bone mass center through the diaphyseal wall (radial distribution). After the 1 year period, there was an overall interaction of group x time in bone mineral density (BMD) at the proximal femur (p = 0.05) and tibial shaft (p = 0.035). Women in the ExHRT and HRT groups had increased proximal femur and tibial shaft BMD when compared with the change observed in the Co group (p = 0.024-0.011). The change was more pronounced in the cortical tibia, wherein the ExHRT group also differed from the Ex group (p = 0.038). No significant changes were found in bone CSA at any of the measured sites. The radial distribution indicated an increase of BMD in the endocortical part of the measured sites in the HRT and ExHRT groups and in the proximal tibia in the Ex group. The polar distribution showed that bone mass was redistributed in the anteroposterior direction. The changes in I(max), I(min), and I(polar) in the HRT and ExHRT groups differed from those in the Co group at the proximal femur, midfemur, and proximal tibia (p = 0.047-0.001). The Ex group also differed from the Co group in I(max) and I(polar) at the proximal tibia (p = 0.018 and 0.039, respectively). These results support the idea that HRT acts primarily at the bone-marrow interface. The exercise intervention chosen for this study contributed to the maintenance of bone mass. Our results suggest that both HRT and exercise have local effects on bone mass. The change in bone mass distribution induced by HRT and exercise may play an important role in the alteration of bone strength.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Analysis_of_Variance_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12123333
----K E
----T Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study.
----A BACKGROUND: Hot flashes are frequent in postmenopausal breast cancer patients, especially when treated with tamoxifen. Estrogen replacement therapy is the most effective treatment for hot flashes, but its use is controversial in breast cancer survivors. Progestins may offer a good alternative for the control of hot flashes in this setting; in particular, oral megestrol acetate has been proven effective in a randomized, placebo-controlled clinical trial. With the aim of further improving these results, we have designed a randomized study comparing oral megestrol acetate with depot intramuscular (i.m.) medroxyprogesterone acetate (MPA) for the control of hot flashes in postmenopausal patients with a history of breast cancer. PATIENTS AND METHODS: Seventy-one postmenopausal patients were randomized to receive an i.m. injection of depot MPA 500 mg on days 1, 14 and 28, or oral megestrol acetate 40 mg daily for 6 weeks. Patients recorded daily the number and severity of their hot flashes; response was defined as a > or =50% decrease in the number and severity of hot flashes. RESULTS: At week 6, hot flashes were reduced by 86% on average in the whole group of patients, without significant differences between the two progestins. Response was obtained by 75 and 67% of patients receiving MPA or megestrol, respectively (P = 0.5). Responders were followed to assess maintenance of response (without further treatment), which was significantly better with i.m. MPA: in this group, 89% of responders still showed a benefit at week 24, compared with 45% in the megestrol group (P = 0.03). CONCLUSIONS: Our study shows that a short cycle of i.m. depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer, offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Aged_MeSH M_Breast_Neoplasms_MeSH S_complications_MeSH Breast_Neoplasms_complications_MeSH S_diagnosis_MeSH Breast_Neoplasms_diagnosis_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH M_Chi-Square_Distribution_MeSH M_Comparative_Study_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Administration_Schedule_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hot_Flashes_MeSH S_complications_MeSH Hot_Flashes_complications_MeSH S_diagnosis_MeSH Hot_Flashes_diagnosis_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Injections__Intramuscular_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Megestrol_Acetate_MeSH S_administration_&_dosage_MeSH Megestrol_Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Postmenopause_MeSH M_Probability_MeSH M_Reference_Values_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12161047
----K E
----T Six months of hormone replacement therapy does not influence muscle strength in postmenopausal women.
----A OBJECTIVES: Postmenopausal hormone replacement therapy (HRT) has positive effects on fracture incidence before any effects on bone mineral density can be demonstrated. This has been attributed to increased muscle strength by HRT. This study was designed to evaluate the effect of 6 months of HRT on muscle strength in postmenopausal women. METHODS: Forty postmenopausal women, aged 60-78 were included in the study. They were randomly divided in two groups with 20 women in each group. One group received Menorest 50 microg/24 h (estradiol 4.3 mg) and Gestapuran 2.5 mg (medroxyprogesteron) daily and the other group received placebo treatment. The study was conducted as a double blinded, prospective and placebo controlled trial. Hand grip strength, isokinetic knee flexion and extention, and physical activity were measured before treatment, after 3 and 6 months. Physical activity was estimated using a classification system of physical activity. A JAMAR hydraulic hand dynamometer and a Cybex II dynamometer were used to evaluate muscle strength. RESULTS: Hand grip strength in the right hand, increased significantly in both groups (HRT P<0.001 and placebo P<0.01) and in the left hand in the HRT group (P<0.01). However, there were no differences in muscle strength between the two groups. There was no significant change in isokinetic knee flexion or extension after 6 months in either of the groups. The estimated physical activity increased slightly in the placebo group, but there was no significant difference compared to the treatment group. CONCLUSIONS: Our data suggest that 6 months of HRT does not influence muscle strength in postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Body_Mass_Index_MeSH M_Data_Interpretation__Statistical_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hand_Strength_MeSH M_Human_MeSH M_Knee_Joint_MeSH S_drug_effects_MeSH Knee_Joint_drug_effects_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Middle_Aged_MeSH M_Motor_Activity_MeSH S_drug_effects_MeSH Motor_Activity_drug_effects_MeSH M_Muscle_Contraction_MeSH S_drug_effects_MeSH Muscle_Contraction_drug_effects_MeSH M_Muscle__Skeletal_MeSH S_drug_effects_MeSH Muscle__Skeletal_drug_effects_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Time_Factors_MeSH 
****** 12186625
----K E
----T Anastrozole in the management of breast cancer.
----A Anastrozole (Arimidex, AstraZeneca) is a third-generation aromatase inhibitor which rapidly reduces oestradiol concentrations to below detectable levels. It is both potent and selective for the aromatase enzyme, with near-maximal suppression of serum oestrogens occurring at the clinical dose of 1 mg/day in postmenopausal women with advanced breast cancer. Anastrozole has also been shown to be a potent suppressor of intratumoural oestrogens, with responses comparable to those in serum. The results of two large, identically designed, randomised trials in postmenopausal women with advanced breast cancer who had progressed on tamoxifen showed that oral anastrozole 1 mg/day produced a statistically significant survival advantage over megestrol acetate 40 mg q.i.d. The median duration of survival was 26.7 months for anastrozole versus 22.5 months for megestrol acetate. Anastrozole was as well-tolerated as megestrol acetate, while weight gain was significantly increased in the megestrol acetate group compared with the anastrozole group. In another Phase III clinical trial involving 1021 postmenopausal women with advanced breast cancer, anastrozole showed a statistically significant advantage over tamoxifen in median time to progression in a combined analysis of 611 patients who were known to be oestrogen receptor- or progesterone receptor-positive. Anastrozole was as well-tolerated as tamoxifen, with a low rate of withdrawals (2%) due to drug-related adverse events. In addition, anastrozole was associated with fewer thromboembolic events and episodes of vaginal bleeding than tamoxifen. For women with hormone receptor-positive tumours who progress on tamoxifen, anastrozole is superior to megestrol acetate. In addition, anastrozole is a reasonable alternative to tamoxifen for first-line endocrine therapy of advanced breast cancer. Recent data confirm an emerging role for anastrozole as adjuvant therapy for primary breast cancer in postmenopausal patients. Anastrozole is also being investigated in the neoadjuvant setting.
----P Journal_Article Review Review__Tutorial 
----M M_Animals_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH S_metabolism_MeSH Breast_Neoplasms_metabolism_MeSH M_Disease_Management_MeSH M_Drug_Evaluation_MeSH S_methods_MeSH Drug_Evaluation_methods_MeSH S_statistics_&_numerical_data_MeSH Drug_Evaluation_statistics_&_numerical_data_MeSH M_Female_MeSH M_Human_MeSH M_Nitriles_MeSH S_chemistry_MeSH Nitriles_chemistry_MeSH S_pharmacokinetics_MeSH Nitriles_pharmacokinetics_MeSH S_therapeutic_use_MeSH Nitriles_therapeutic_use_MeSH M_Survival_Analysis_MeSH M_Triazoles_MeSH S_chemistry_MeSH Triazoles_chemistry_MeSH S_pharmacokinetics_MeSH Triazoles_pharmacokinetics_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12202468
----K E
----T Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women.
----A OBJECTIVE: To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of relevant articles, and proceedings of international meetings for eligible randomized controlled trials. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. STUDY SELECTION: We included 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of these studies reported fractures. DATA ABSTRACTION: For each study, three independent reviewers assessed the methodological quality and abstracted the data. DATA SYNTHESIS: HRT showed a trend toward reduced incidence of vertebral fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5 trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had a consistent effect on bone mineral density (BMD) at all sites. The difference between HRT and control in the percent change in bone density at 2 yr was 6.76 (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and 4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively. CONCLUSIONS: HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.
----P Journal_Article Meta-Analysis Review Review__Tutorial 
----M P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Randomized_Controlled_Trials_MeSH 
****** 12212785
----K E
----T Estrogen and cognitive functioning in men with mild cognitive impairment.
----A Although men do not experience an abrupt cessation of gonadal hormone production at midlife as do women, levels of testosterone (T) decrease gradually with aging. Because estradiol (E2) arises mainly from the conversion of T in men, the availability of E2 also decreases with increasing age. In randomized clinical trials, E2 replacement therapy has been shown to maintain aspects of cognition in postmenopausal women, specifically with regard to verbal memory. The present prospective, randomized, cross-over trial is being undertaken in order to determine whether E2 will enhance verbal memory in men with Mild Cognitive Impairment (MCI). Men with MCI will randomly receive E2 or placebo for the first 3 mo of treatment and will then be crossed-over to the other treatment for an additional 3 mo. A battery of neuropsychological tests will be administered at pretreatment and, again, following each 3-mo treatment phase. It is hypothesized that elderly men with MCI will perform better on tests of explicit memory when they are being treated with E2 compared to their performance under placebo conditions.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Cognition_Disorders_MeSH S_blood_MeSH Cognition_Disorders_blood_MeSH S_drug_therapy_MeSH Cognition_Disorders_drug_therapy_MeSH S_psychology_MeSH Cognition_Disorders_psychology_MeSH M_Cross-Over_Studies_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Human_MeSH M_Male_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Neuropsychological_Tests_MeSH M_Prospective_Studies_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH M_Treatment_Outcome_MeSH 
****** 12213517
----K E
----T Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase.
----A Estrogen and progesterone interact with monoamines in ways that suggest the potential modulation of responses to psychoactive drugs by endogenous steroids, both between menstrual phases and between the sexes. The present study assessed the subjective and physiological effects of a single dose of D-amphetamine (AMPH; 15 mg oral) in healthy, normally cycling women (n=13), who received amphetamine and placebo (PL) during both the follicular and luteal phases of a single menstrual cycle, and in healthy men (n=7). Females reported greater amphetamine-induced subjective stimulation [Addiction Research Center Inventory (ARCI)-A, ARCI-MBG; Drug Effects Questionnaire (DEQ) Feel Drug, Feel High, Want More] during the follicular phase than the luteal phase. Within the follicular phase, the magnitude of individuals' AMPH-induced stimulation was positively associated with baseline (predrug) salivary estradiol [r=+.55-.78; Profile of Mood States (POMS) Vigor, Positive Mood, Elation], and negatively associated with salivary progesterone [r=-.66-.68; POMS Friendliness; Subjective States Questionnaire (SSQ) Pleasant Sedation]. Sex differences also emerged. Males reported feeling greater AMPH-induced stimulation (ARCI-A, ARCI-MBG; DEQ Feel Drug, Want More) than females in the luteal phase. Thus, higher levels of estrogen and lower levels of progesterone are associated with greater subjective stimulation after AMPH in women, and these hormonal influences contribute to sex differences in amphetamine responding.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH S_physiology_MeSH Affect_physiology_MeSH M_Analysis_of_Variance_MeSH M_Comparative_Study_MeSH M_Cross-Over_Studies_MeSH M_Dextroamphetamine_MeSH S_pharmacology_MeSH Dextroamphetamine_pharmacology_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_metabolism_MeSH Estradiol_metabolism_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH M_Menstrual_Cycle_MeSH S_drug_effects_MeSH Menstrual_Cycle_drug_effects_MeSH S_metabolism_MeSH Menstrual_Cycle_metabolism_MeSH S_psychology_MeSH Menstrual_Cycle_psychology_MeSH M_Progesterone_MeSH S_metabolism_MeSH Progesterone_metabolism_MeSH P_Sex_Characteristics_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12218381
----K E
----T Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women.
----A OBJECTIVES: To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women. METHODS: Participants were tested with a randomized, double-blind design on the Identical Pictures, Cube Comparisons, Building Memory and Shape Memory tasks before and after 4 months of hormone treatment. RESULTS: Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task, whereas those receiving estrogen alone showed a decrease in performance. CONCLUSIONS: These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estradiol_Congeners_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Methyltestosterone_MeSH S_administration_&_dosage_MeSH Methyltestosterone_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH P_Postmenopause_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12218721
----K E
----T Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study.
----A OBJECTIVE: To investigate the effect of an oral soy isoflavone extract (Phytosoya) on hot flushes in menopausal women. DESIGN: The study was conducted on outpatients according to a multicenter, randomized, double-blind, placebo-controlled, parallel-group design. A total of 75 patients in natural or surgical menopause suffering from at least seven hot flushes per day were randomized to receive during 4 months either soy isoflavone extract (total of 70 mg genistin and daidzin per day) or placebo. RESULTS: There is evidence to suggest that 16 weeks of treatment with soy extract can help reduce the mean number of hot flushes per 24 hours in menopausal women. Withdrawals during this trial made it difficult to obtain an unbiased estimate of the true treatment effect, but numerous sensitivity analyses lend support to the suggestion that taking soy extract can be beneficial in the treatment of hot flushes. In particular, women taking soy extract had a 38% reduction in the mean number of hot flushes by week 4 and a 51% reduction by week 8. By the end of week 16, patients taking soy extract had a 61% reduction in their daily hot flushes versus a 21% reduction obtained with the placebo. "Responders" (defined as patients whose hot flushes were reduced by at least 50% at the end of treatment period) were 65.8% in the soy extract group and 34.2% in the placebo group ( < 0.005). CONCLUSION: Soy isoflavone extract may help to reduce the frequency of hot flushes in climacteric women and provides an attractive addition to the choices available for relief of hot flushes.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Non-Steroidal_MeSH S_pharmacology_MeSH Estrogens__Non-Steroidal_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Isoflavones_MeSH S_pharmacology_MeSH Isoflavones_pharmacology_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Plant_Extracts_MeSH S_pharmacology_MeSH Plant_Extracts_pharmacology_MeSH S_therapeutic_use_MeSH Plant_Extracts_therapeutic_use_MeSH M_Postmenopause_MeSH P_Soybeans_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12218723
----K I
----T Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in healthy, postmenopausal women.
----A OBJECTIVE: To determine the lowest effective dose of an estradiol (E ) matrix-type transdermal delivery system (EMTDS; Alora) for preventing bone loss in postmenopausal women. DESIGN: This double-blind, double-dummy, randomized, placebo-controlled, multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier. Participants were randomly assigned to one of three doses of the EMTDS (0.025, 0.05, or 0.075 mg/day) or placebo administered twice weekly. Lumbar bone mineral density (LBMD) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment. Safety was assessed at regularly scheduled visits. RESULTS: EMTDS provided statistically significant and clinically meaningful changes in LBMD relative to placebo. At 2 years, LBMD declined from baseline by 0.59% in the placebo group, but it increased from baseline by 1.65% ( = 0.0065), 4.08% ( = 0.0001), and 4.82% ( = 0.0001) in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. The corresponding responder rates (defined as no change or increase in LBMD at endpoint) were 39.7% for placebo, 59.6%, 79.3%, and 83.9% in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. Mean serum E concentrations were proportional to the dose of the E transdermal system and did not accumulate over the course of the study. Adverse events were generally comparable across treatment groups, with the majority being mild or moderate in severity and unrelated to study medication. Mammogram findings and other safety assessments were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E treatment. CONCLUSIONS: The EMTDS (Alora) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women, with the benefit of treatment evident by 1 year. The lowest effective dose is 0.025 mg/day.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH P_Drug_Delivery_Systems_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Hysterectomy_MeSH M_Lumbar_Vertebrae_MeSH S_metabolism_MeSH Lumbar_Vertebrae_metabolism_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_blood_MeSH Osteoporosis__Postmenopausal_blood_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Postmenopause_MeSH M_Skin_Absorption_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12225339
----K E
----T Prospective randomised trial comparing diethylstilboestrol and flutamide in the treatment of hormone relapsed prostate cancer.
----A BACKGROUND: Patients with hormone relapsed prostate cancer (HRPC) are often treated with flutamide or diethylstilboestrol. However, which of these two options is the best treatment for HRPC remains unclear. METHODS: We carried out a prospective study to determine and compare the prostate-specific antigen (PSA) response and survival in patients with hormone relapsed prostate cancer (HRPC), all of whom had previously shown a good response to medical or surgical castration. The patients were randomised to treatment with diethylstilboestrol (DES) and aspirin, or the antiandrogen flutamide. In addition, quality of life was determined by interview and questionnaire. RESULTS: Twenty-eight patients were randomised for treatment options.There was a significantly greater fall in the PSA (65% vs 35%; P = 0.034) after treatment with diethylstilboestrol compared to treatment with flutamide. Median survival also rose after treatment with diethylstilboestrol (18 months) compared to flutamide (11 months), but this difference did not reach statistical significance. There was no difference in the quality of life parameters between the two groups. There were no cardiovascular complications in the stilboestrol group. CONCLUSIONS: In HRPC, treatment with stilboestrol is associated with a greater PSA fall and an increase in median survival when compared to flutamide treatment.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Androgen_Antagonists_MeSH S_administration_&_dosage_MeSH Androgen_Antagonists_administration_&_dosage_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_administration_&_dosage_MeSH Antineoplastic_Agents__Hormonal_administration_&_dosage_MeSH M_Comparative_Study_MeSH M_Diethylstilbestrol_MeSH S_administration_&_dosage_MeSH Diethylstilbestrol_administration_&_dosage_MeSH M_Flutamide_MeSH S_administration_&_dosage_MeSH Flutamide_administration_&_dosage_MeSH M_Human_MeSH M_Male_MeSH M_Neoplasm_Recurrence__Local_MeSH M_Prospective_Studies_MeSH M_Prostate-Specific_Antigen_MeSH S_blood_MeSH Prostate-Specific_Antigen_blood_MeSH M_Prostatic_Neoplasms_MeSH S_drug_therapy_MeSH Prostatic_Neoplasms_drug_therapy_MeSH S_mortality_MeSH Prostatic_Neoplasms_mortality_MeSH M_Survival_Rate_MeSH 
****** 12362928
----K E
----T An evaluation of bioequivalence of two 7-day 17beta-estradiol transdermal delivery systems by anatomical site.
----A An open-label, randomized, crossover study was conducted to assess the bioequivalence of two 7-day transdermal 17beta-estradiol delivery systems following application to the buttock in 42 postmenopausal women. The systems tested were a generic Estradiol Transdermal System (Mylan Pharmaceuticals, Inc.) and Climara (Berlex Laboratories, Inc.), the reference product. Each system was labeled to deliver 17beta-estradiol 0.1 mg/day and was applied for 7 days. Serial serum samples were assayed for estradiol, estrone, and estrone sulfate using validated assays. The bioequivalence confidence intervals for the ratio of log-transformed 17beta-estradiol Cmax values for the Estradiol Transdermal System and Climara were outside the interval of 0.80 to 1.25, indicating that the products were not bioequivalent. Application site reactions and skin irritation were more common with the Estradiol Transdermal System than with Climara. The odds of patch lifting or detachment were 6.95 times higher with the Estradiol Transdermal System than with Climara. Because these two transdermal delivery systems had been previously shown to be bioequivalent after application to the abdomen, the findings of this study suggest that bioequivalence at one anatomical site is not indicative of bioequivalence at another.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Area_Under_Curve_MeSH M_Buttocks_MeSH M_Comparative_Study_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_pharmacokinetics_MeSH Estradiol_pharmacokinetics_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrone_MeSH S_analogs_&_derivatives_MeSH Estrone_analogs_&_derivatives_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Therapeutic_Equivalency_MeSH 
****** 12419083
----K E
----T Efficacy and tolerability of pulsed estrogen therapy: a 12-week double-blind placebo-controlled study in highly symptomatic postmenopausal women.
----A OBJECTIVE: To confirm the efficacy and safety of pulsed estrogen therapy, a transient daily hormone exposure, for climacteric symptoms in highly symptomatic postmenopausal women. Patients and methods: In this multicenter, double-blind, parallel-group study, early postmenopausal women with at least seven moderate to severe vasomotor symptoms per day were randomized to receive intranasal estradiol, 150 or 300 microg/day, or placebo, for 12 weeks. The primary outcome measure was the mean daily number of moderate to severe vasomotor symptoms, as recorded in patient diaries. RESULTS: A total of 165 patients were randomized. The mean daily number of moderate to severe vasomotor symptoms decreased significantly more (p < 0.001) in the 150-microg/day (-7.86) and 300-microg/day (-9.39) groups than in the placebo group (-5.22). The decrease reached significance more rapidly with the 300-microg/day dose (from week 2) than with the 150-microg/day dose (from week 8). The rate of emergent adverse events with both doses was similar to that with placebo. CONCLUSIONS: Pulsed estrogen therapy, achieved by intranasal estradiol 150 microg/day and 300 microg/day, significantlyreduced the incidence of moderate to severe vasomotor symptoms, compared with placebo. The 300-microg/day dose demonstrated a greater and more rapid therapeutic effect, with no clinically significant difference in tolerability, compared with the 150-microg/day dose, and therefore offers the best efficacy/safety ratio when initiating treatment with intranasal estradiol.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intranasal_MeSH M_Adult_MeSH M_Aged_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_France_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Pulse_Therapy__Drug_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12427399
----K E
----T Clinical equivalence of intranasal estradiol and oral estrogens for postmenopausal symptoms.
----A OBJECTIVES: The aim was to demonstrate the equivalent efficacy of intranasal estradiol (Aerodiol Servier, Istanbul, Turkey) 300 mg/day relative to a standard oral estradiol therapy of 2 mg/day and to assess the therapeutic value of the potential benefits of Aerodiol. METHODS: Two hundred and one postmenopausal women with severe menopausal symptoms were recruited to the trial. Women received either intranasal Aerodiol 300 microg/day (one spray delivery of 150 microg per nostril) or an oral estradiol 2 mg for 24 weeks. Severity of symptoms were compared based on the Kupperman index (KI) at the end of 24 weeks. RESULTS: The KI score decreased markedly in both groups between W0 and W24. At W24, the two treatments were shown to be statistically equivalent (P<0.001). The incidence of adverse events was very similar in both groups; those related to treatment were of mild or moderate intensity in 95% of cases for the nasal group and 90% for the oral group. CONCLUSIONS: In conclusion, pulsed estrogen therapy using Aerodiol is safe, easily used and highly efficient in alleviating postmenopausal symptoms with a dose of 300 microg. The dose of 300 microg in one administration per day offers the optimal therapy whilst being easily adaptable to each patient's clinical response.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Intranasal_MeSH M_Administration__Oral_MeSH M_Anxiety_MeSH S_drug_therapy_MeSH Anxiety_drug_therapy_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Prospective_Studies_MeSH M_Severity_of_Illness_Index_MeSH M_Sleep_Initiation_and_Maintenance_Disorders_MeSH S_drug_therapy_MeSH Sleep_Initiation_and_Maintenance_Disorders_drug_therapy_MeSH M_Sweating_MeSH S_drug_effects_MeSH Sweating_drug_effects_MeSH 
****** 12428992
----K E
----T Hormone replacement therapy: optimising the dose and route of administration.
----A Several new products and regimens for estrogen replacement in the postmenopausal woman have recently been introduced, giving physicians and patients greater choice not only in dose but also in route of administration. Estrogen treatment in the postmenopausal woman has several proven benefits for those who have vasomotor symptoms or problems related to urogenital atrophy. However, the most controversial area is in the long-term preventive benefits of estrogen against the development of osteoporosis and cardiovascular disease, particularly in women older than 60 years. It is in these areas that decisions on the dose and optimal route of administration of estrogen replacement therapy (ERT) must be made. Although adding a progestogen to an ERT regimen is mandatory, particularly in a woman with an intact uterus, discussion now focuses on which progestogen least attenuates the beneficial effects of estrogen. Emerging trends suggest that lower doses of estrogen (i.e. ethinylestradiol 5 microg/day, estradiol 0.25 mg/day or conjugated estrogens [CEE] 0.3 mg/day) continuously combined with lower doses of medroxyprogesterone (MPA) are equally effective at relieving vasomotor symptoms as the most commonly prescribed regimen in the US (CEE 0.625mg/MPA 2.5mg daily), with fewer adverse events, leading to greater patient acceptance and likelihood for continuation of therapy. This is especially important when therapy is initiated at an older age.
----P Journal_Article Review Review__Tutorial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Aged_MeSH M_Cardiovascular_Diseases_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_adverse_effects_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Randomized_Controlled_Trials_MeSH 
****** 12443837
----K E
----T Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women.
----A OBJECTIVE: Selective estrogen receptor modulators (SERMs) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific. Ospemifene (FC-1271a) is a novel SERM compound, which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system, while having antiestrogen-like effects in uterus and breast. In this study, we investigated the effects of ospemifene on the uterine endometrium, vaginal maturation index and hormonal status in healthy postmenopausal women. METHODS: The study was conducted as a double-blind, placebo-controlled phase I study, where 40 healthy postmenopausal women volunteers were randomized to receive daily oral doses of ospemifene either 25, 50, 100 or 200 mg or placebo for 12 weeks. Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks' visit. Serum concentrations of estradiol, luteinizing hormone, follicle stimulating hormone (FSH), sex-hormone binding globulin (SHBG), parathyroid hormone and prolactin were determined from samples taken at baseline, at 4 days and at 4, 12, and 16 weeks' visits. Climacteric symptoms were assessed using 12 visual analogue scales (VAS) at baseline and at the end of the study. RESULTS: No clinically significant changes were seen in endometrial thickness at any dose level. Ospemifene exerted a very weak estrogenic effect on endometrial histology. On the other hand, it induced a clear estrogenic effect on vaginal epithelium. Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes; FSH decreased and SHBG increased during the treatment. In general, ospemifene was well tolerated. The 25 and 50 mg doses tended to reduce climacteric symptoms, but no statistically significant differences were observed between different doses of ospemifene and placebo. The highest dose level (200 mg) induced more subjective adverse reactions, especially hot flushes, than lower doses. CONCLUSION: Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg. Further studies are needed to substantiate the results of this Phase I pilot study.
----P Clinical_Trial Clinical_Trial__Phase_I Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Aged_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH S_drug_effects_MeSH Luteinizing_Hormone_drug_effects_MeSH M_Middle_Aged_MeSH M_Pain_Measurement_MeSH M_Parathyroid_Hormone_MeSH S_blood_MeSH Parathyroid_Hormone_blood_MeSH M_Postmenopause_MeSH M_Prolactin_MeSH S_blood_MeSH Prolactin_blood_MeSH S_drug_effects_MeSH Prolactin_drug_effects_MeSH M_Reference_Values_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_drug_effects_MeSH Sex_Hormone-Binding_Globulin_drug_effects_MeSH M_Tamoxifen_MeSH S_administration_&_dosage_MeSH Tamoxifen_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Tamoxifen_analogs_&_derivatives_MeSH S_pharmacology_MeSH Tamoxifen_pharmacology_MeSH S_therapeutic_use_MeSH Tamoxifen_therapeutic_use_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_ultrasonography_MeSH Vagina_ultrasonography_MeSH 
****** 12449905
----K E
----T Health risks outweigh benefits for combined estrogen plus progestin. Clinical trial stopped early in major study.
----A 
----P News 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH M_Cerebrovascular_Accident_MeSH S_epidemiology_MeSH Cerebrovascular_Accident_epidemiology_MeSH M_Colorectal_Neoplasms_MeSH S_prevention_&_control_MeSH Colorectal_Neoplasms_prevention_&_control_MeSH M_Coronary_Disease_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Drug_Combinations_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Hip_Fractures_MeSH S_prevention_&_control_MeSH Hip_Fractures_prevention_&_control_MeSH P_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH P_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH M_Time_Factors_MeSH M_Venous_Thrombosis_MeSH S_epidemiology_MeSH Venous_Thrombosis_epidemiology_MeSH 
****** 12450599
----K E
----T Baseline characteristics of participants in the Raloxifene Use for The Heart (RUTH) trial.
----A The Raloxifene Use for The Heart (RUTH) trial is a randomized, placebo-controlled, double-blind trial designed to determine whether raloxifene 60 mg/day compared with placebo lowers the risk of coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI) and reduces the risk of invasive breast cancer in women at risk for a major coronary event. Raloxifene is a selective estrogen receptor modulator that improves cardiovascular risk factors, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. Between June 1998 and August 2000, 10,101 women were enrolled at 187 sites in 26 countries. Approximately half of the women had documented coronary heart disease (CHD) (n = 5,031); the remainder had multiple CHD risk factors that increased their risk for a CHD event (n = 5,070). The mean age of participants was 68 years (39% were >70 years old), and did not differ between those with documented CHD and those at increased CHD risk. Most women were Caucasian (84%); 60% had a body mass index >/=27 kg/m(2), 46% had diabetes mellitus, 78% had systemic hypertension, and 14% had low-density lipoprotein cholesterol >160 mg/dl. Compared with women at increased CHD risk, women with documented CHD had higher cardiovascular risk scores, a higher prevalence of abnormal electrocardiograms, greater use of cardiovascular medications, were more likely to have had cardiac rehabilitation, and were more likely to have previously used estrogen or oral contraceptives, but had a slightly lower prevalence of CHD risk factors such as smoking, obesity, diabetes mellitus, and systemic hypertension, and had lower serum levels of total and low-density lipoprotein cholesterol. The RUTH cohort is the largest group of postmenopausal women at increased risk of CHD events ever assembled in a clinical trial, and is the first trial designed to determine the effect of a selective estrogen receptor modulator on the risk of CHD events.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH S_prevention_&_control_MeSH Breast_Neoplasms_prevention_&_control_MeSH M_Coronary_Disease_MeSH S_drug_therapy_MeSH Coronary_Disease_drug_therapy_MeSH S_epidemiology_MeSH Coronary_Disease_epidemiology_MeSH S_prevention_&_control_MeSH Coronary_Disease_prevention_&_control_MeSH M_Double-Blind_Method_MeSH M_Estrogen_Antagonists_MeSH S_administration_&_dosage_MeSH Estrogen_Antagonists_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogen_Antagonists_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Myocardial_Infarction_MeSH S_prevention_&_control_MeSH Myocardial_Infarction_prevention_&_control_MeSH M_Patient_Selection_MeSH M_Postmenopause_MeSH M_Raloxifene_MeSH S_administration_&_dosage_MeSH Raloxifene_administration_&_dosage_MeSH S_therapeutic_use_MeSH Raloxifene_therapeutic_use_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12454761
----K E
----T A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers.
----A While tamoxifen use is associated with clear benefits in the treatment of hormone-sensitive breast cancer, it also exhibits partial oestrogen agonist activity that is associated with adverse events, including endometrial cancer. Fulvestrant ("Faslodex") is a new oestrogen receptor antagonist that downregulates the oestrogen receptor and has no known agonist effect. This single-centre, double-blind, randomised, parallel-group trial was conducted to determine the direct effects of fulvestrant on the female endometrium when given alone and in combination with the oestrogen, ethinyloestradiol. Following a 14-day, pretrial screening period, 30 eligible postmenopausal volunteers were randomised to receive fulvestrant 250 mg, fulvestrant 125 mg or matched placebo administered as a single intramuscular injection. Two weeks postinjection, volunteers received 2-weeks concurrent exposure to ethinyloestradiol 20 microg day(-1). Endometrial thickness was measured before and after the 14-day screening period with further measurements predose (to confirm a return to baseline) and on days 14, 28 and 42 post-treatment with fulvestrant. Pharmacokinetic and safety assessments were performed throughout the trial. Fulvestrant at a dose of 250 mg significantly (P=0.0001) inhibited the oestrogen-stimulated thickening of the endometrium compared with placebo. Neither the 125 mg nor 250 mg doses of fulvestrant demonstrated oestrogenic effects on the endometrium over the initial 14-day assessment period. Fulvestrant was well tolerated and reduced the incidence of ethinyloestradiol-related side effects. At the same dose level that is being evaluated in clinical trials of postmenopausal women with advanced breast cancer, fulvestrant (250 mg) is an antioestrogen with no evidence of agonist activity in the endometrium of healthy postmenopausal women.
----P Clinical_Trial Clinical_Trial__Phase_I Journal_Article Randomized_Controlled_Trial 
----M M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_pharmacokinetics_MeSH Estradiol_pharmacokinetics_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogen_Antagonists_MeSH S_pharmacokinetics_MeSH Estrogen_Antagonists_pharmacokinetics_MeSH S_pharmacology_MeSH Estrogen_Antagonists_pharmacology_MeSH M_Estrogen_Receptor_Modulators_MeSH S_pharmacokinetics_MeSH Estrogen_Receptor_Modulators_pharmacokinetics_MeSH S_pharmacology_MeSH Estrogen_Receptor_Modulators_pharmacology_MeSH M_Ethinyl_Estradiol_MeSH S_pharmacology_MeSH Ethinyl_Estradiol_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Safety_MeSH 
****** 12466335
----K E
----T Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women.
----A Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (+/-SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 +/- 39%) and 100-mg dose groups (242 +/- 184%) than in the control group (-29 +/- 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 +/- 72%) and 100-mg dose groups (116 +/- 119%) than in the control group (-5 +/- 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 +/- 17%, 2.8 +/- 34%, -11 +/- 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 +/- 146%) and 100-mg dose groups (457 +/- 601%) than in the control group (-27 +/- 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during long-term administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Androstenedione_MeSH S_administration_&_dosage_MeSH Androstenedione_administration_&_dosage_MeSH S_therapeutic_use_MeSH Androstenedione_therapeutic_use_MeSH M_Area_Under_Curve_MeSH M_Control_Groups_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12466367
----K E
----T Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men.
----A We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after a baseline (B) study in randomized order with an intervening 3-month washout: transdermal T patch (5.0 mg/daily); recombinant human GH (6.25 micro g/kg sc daily); and combined hormones (GHT). ANOVA with repeated measures was used to evaluate interventional effects. Integrated serum GH concentrations [mean (SEM)] were elevated comparably by GH and GHT: [B = 363 (55), GH = 1107 (120), T = 459 (131), and GHT = 1189 (46) micro g/liter.min; P < 0.0001]. Serum IGF-I concentrations also increased commensurately after GH and GHT: [B = 168 (14), GH = 285 (16), T = 192 (25), and GHT = 294 (25) micro g/liter; P < 0.0001]. GHT administration increased total estradiol: [B = 110 (20), GH = 106 (13), T = 129 (13), and GHT = 153 (17) pmol/liter; P < 0.02], and both T and GHT elevated free T: [B = 12 (2.1), GH = 11 (1.5), T = 22 (2.8), and GHT = 24 (2.5) pg/ml; P < 0.0001]. No significant changes occurred in strength, flexibility, percentage body fat, or sexual function and mood. However, fat-free mass increased under combined GHT exposure: [B = 55 (1.3), GH = 56 (1.1), T = 55 (1.5), GHT = 57 (1.7) kg; P < 0.03]. Balance improved in response to GH intervention (P < 0.05), as did 30-m walk time during T and GHT interventions [B = 6.6 (0.3), GH = 6.2 (0.7), T = 5.9 (0.3), GHT = 5.5 (0.3) sec; P = 0.04] and stair climb time for all three interventions [B = 32.2 (1.4), GH = 29.8 (1.2), T = 30.5 (1.4), and GHT = 29.9 (1.2) sec (P = 0.0034), wherein the effects of GH, T, and GHT were different from that of B]. Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration (P < 0.05, compared with B). Myostatin and androgen receptor gene expression were not affected. Serum osteocalcin increased in response to the GH and GHT interventions: [B = 4.8 (0.52), GH = 5.7 (0.54), T = 4.7 (0.33), and GHT = 5.5 (0.39); P <0.009]. There were no significant adverse events during 30 patient-months of intervention. We conclude that 1 month of GH and/or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Aged_MeSH M_Body_Composition_MeSH S_drug_effects_MeSH Body_Composition_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Gene_Expression_MeSH S_drug_effects_MeSH Gene_Expression_drug_effects_MeSH M_Human_MeSH M_Human_Growth_Hormone_MeSH S_blood_MeSH Human_Growth_Hormone_blood_MeSH S_secretion_MeSH Human_Growth_Hormone_secretion_MeSH S_therapeutic_use_MeSH Human_Growth_Hormone_therapeutic_use_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_analysis_MeSH Insulin-Like_Growth_Factor_I_analysis_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Muscle__Skeletal_MeSH S_physiology_MeSH Muscle__Skeletal_physiology_MeSH M_Musculoskeletal_Equilibrium_MeSH S_drug_effects_MeSH Musculoskeletal_Equilibrium_drug_effects_MeSH P_Physical_Fitness_MeSH M_Recombinant_Proteins_MeSH S_therapeutic_use_MeSH Recombinant_Proteins_therapeutic_use_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Sexual_Behavior_MeSH S_drug_effects_MeSH Sexual_Behavior_drug_effects_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_adverse_effects_MeSH Testosterone_adverse_effects_MeSH S_blood_MeSH Testosterone_blood_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH 
****** 12468135
----K E
----T Bleeding patterns in peri and postmenopausal women taking a continuous combined regimen of estradiol with norethisterone acetate or a conventional sequential regimen of conjugated equine estrogens with medrogestone.
----A OBJECTIVES: The aim of this study was to compare the incidence of women presenting irregular bleeding episodes following 9 months of treatment with a low dose continuous combined hormone replacement therapy consisting of estradiol (E(2)) and norethisterone acetate (NETA) versus a sequential hormone replacement therapy consisting of conjugated equine estrogens (CEE) and medrogestone (MG). Secondary aims were to establish the relationship between menopausal age and the occurrence of irregular bleeding for both therapies and to assess the efficacy of both therapies in alleviating menopausal symptoms. METHODS: This was a stratified and randomised, open label study conducted with late peri and postmenopausal women at 35 sites in Austria and Germany. A total of 446 women were randomly allocated into two cohorts based on time since last bleeding and then stratified to either a low dose continuous combined therapy consisting of 1 mg E(2) and 0.5 mg NETA for 28 days or a sequential therapy consisting of 0.625 mg CEE for 28 days and 5 mg MG for the final 14 days. Bleeding and menopausal complaints were continuously assessed. Treatments were administered for 9 lunar months. RESULTS: The incidence rate of women presenting irregular bleeding episodes including spotting during cycle 9 was 12.2% with 1mgE(2)/0.5mgNETA and 25.8% with 0.625mgCEE/5mgMG (P = 0.0014). In the group of postmenopausal women (time since last bleeding > or = 12 months) the incidence of irregular bleeding during cycle 9 was 11.0% for 1mgE(2)/0.5mgNETA and 25.0% for 0.625mgCEE/5mgMG). In the group of late perimenopausal women (time since last bleeding 6-11 months) the incidence of irregular bleeding was similar for both treatments at cycle 3, but markedly less in patients with 1mgE(2)/0.5mgNETA at cycle 6 and 9, being significantly different compared to patients with 0.625mgCEE/5mgMG at cycle 6 (P < 0.05). The cumulative rate of amenorrhea (no bleeding or spotting) achieved with 1mgE(2)/0.5mgNETA was 89% for the postmenopausal women and 83.7% for the late perimenopausal women. Both treatments relieved menopausal complaints equally effective. CONCLUSIONS: Regarding the occurrence of irregular bleeding, the low dose continuous combined therapy was superior to the sequential therapy (0.625mgCEE/5mgMG). The low dose continuous combined E(2)/NETA regimen is also suitable for late perimenopausal women since more than 80% of the women had no bleeding or spotting after 9 months of treatment.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Austria_MeSH M_Cohort_Studies_MeSH M_Comparative_Study_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Therapy__Combination_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Germany_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Medrogestone_MeSH S_administration_&_dosage_MeSH Medrogestone_administration_&_dosage_MeSH S_adverse_effects_MeSH Medrogestone_adverse_effects_MeSH S_therapeutic_use_MeSH Medrogestone_therapeutic_use_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Prospective_Studies_MeSH M_Treatment_Outcome_MeSH M_Uterine_Hemorrhage_MeSH S_chemically_induced_MeSH Uterine_Hemorrhage_chemically_induced_MeSH S_pathology_MeSH Uterine_Hemorrhage_pathology_MeSH 
****** 12468165
----K E
----T Menopausal symptoms in older women and the effects of treatment with hormone therapy.
----A OBJECTIVE: In some women, hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses. The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented. METHODS: We used data from the Heart and Estrogen/Progestin Replacement Study, a blinded, clinical trial among 2763 women with documented coronary disease and a uterus who were randomized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo. Participants were queried at baseline and annually regarding menopausal symptoms. Breast symptoms were self-reported, and uterine bleeding was recorded on a daily diary. RESULTS: Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants, whose average age was 67 years and who averaged 18 years since menopause. At baseline, 16% of women reported frequent hot flashes, 26% vaginal dryness, 10% genital irritation, 55% trouble sleeping, and 53% early awakening. Women assigned to hormone therapy reported less frequent hot flashes, vaginal dryness, and trouble sleeping compared with women assigned to placebo, but more frequent vaginal discharge, genital irritation, uterine bleeding, and breast symptoms. The reporting of breast symptoms among women in the hormone group decreased from 40% at 1 year to 13% by the 4th year. Uterine bleeding was reported by 31% and spotting by an additional 33% of women in the hormone group during the 1st year of treatment; by the 4th year, these proportions had fallen to 11% and 20%, respectively. CONCLUSION: Symptoms typically attributed to menopause are common in elderly women. Postmenopausal hormone therapy reduces hot flashes, trouble sleeping, and vaginal dryness, but at standard doses in elderly women is associated with vaginal discharge, genital irritation, uterine bleeding, and breast symptoms.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Age_Factors_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Cardiovascular_Diseases_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Cohort_Studies_MeSH M_Comparative_Study_MeSH M_Confidence_Intervals_MeSH M_Evaluation_Studies_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Hot_Flashes_MeSH S_diagnosis_MeSH Hot_Flashes_diagnosis_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_epidemiology_MeSH Hot_Flashes_epidemiology_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Probability_MeSH M_Prognosis_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Assessment_MeSH M_Risk_Factors_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12472620
----K E
----T Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men.
----A This study was a 12-week double blind placebo-controlled, randomized, parallel trial in which active treatment with different doses of Maca Gelatinizada was compared with placebo. The study aimed to demonstrate if effect of Maca on subjective report of sexual desire was because of effect on mood or serum testosterone levels. Men aged 21-56 years received Maca in one of two doses: 1,500 mg or 3,000 mg or placebo. Self-perception on sexual desire, score for Hamilton test for depression, and Hamilton test for anxiety were measured at 4, 8 and 12 weeks of treatment. An improvement in sexual desire was observed with Maca since 8 weeks of treatment. Serum testosterone and oestradiol levels were not different in men treated with Maca and in those treated with placebo (P:NS). Logistic regression analysis showed that Maca has an independent effect on sexual desire at 8 and 12 weeks of treatment, and this effect is not because of changes in either Hamilton scores for depression or anxiety or serum testosterone and oestradiol levels. In conclusion, treatment with Maca improved sexual desire.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Human_MeSH P_Lepidium_MeSH M_Male_MeSH M_Middle_Aged_MeSH P_Phytotherapy_MeSH M_Placebos_MeSH M_Reference_Values_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12479631
----K E
----T The pattern of alveolar crest height change in healthy postmenopausal women after 3 years of hormone/estrogen replacement therapy.
----A BACKGROUND: The loss of ovarian function at menopause is associated with loss of postcranial and oral bone. Hormone/estrogen replacement therapy (HRT/ERT) has a positive effect on both postcranial and oral bone. The objective of the study was to determine if the positive effect of HRT/ERT on alveolar crest height (ACH) is generalized or site specific. METHODS: The sample consisted of 49 women who completed a 3-year, HRT/ERT prospective study. Cemento-enamel junction distances (ACH) were measured on digitized images of bitewing radiographs. Lumbar spine and proximal femur bone mineral densities (BMDs) were determined with dual-energy x-ray absorptiometric scans. Measurements were made at baseline and at the end of year 3. For the 3-year study period, mean change in ACH was determined for each patient. In addition, the sites with the greatest, second and third greatest ACH changes were determined for each patient. Correlations between changes in ACH (as determined by the various methods) and postcranial BMD were determined. RESULTS: Mean ACH changes had an average correlation (r) of -0.24 with femoral and lumbar spine BMDs. Although the largest site-specific change in ACH resulted in a mean correlation of -0.21, the correlations for the second and third largest changes in ACH dropped to -0.15 and -0.12. Overall, the correlations for site-specific changes were substantively smaller than those for generalized change. CONCLUSIONS: The data of this study indicate that ACH change attributable to HRT/ERT is generalized rather than site specific. Studies of the effect of HRT/ERT on ACH should employ multiple measurements to minimize measurement errors associated with site-specific measurements.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Alveolar_Bone_Loss_MeSH S_drug_therapy_MeSH Alveolar_Bone_Loss_drug_therapy_MeSH S_radiography_MeSH Alveolar_Bone_Loss_radiography_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Regeneration_MeSH S_drug_effects_MeSH Bone_Regeneration_drug_effects_MeSH M_Densitometry__X-Ray_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Femur_MeSH S_drug_effects_MeSH Femur_drug_effects_MeSH S_radiography_MeSH Femur_radiography_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH S_radiography_MeSH Lumbar_Vertebrae_radiography_MeSH M_Medroxyprogesterone_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_physiopathology_MeSH Osteoporosis__Postmenopausal_physiopathology_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Prospective_Studies_MeSH M_Radiography__Bitewing_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12482109
----K E
----T Pulsed estrogen therapy: relieving climacteric symptoms, preventing postmenopausal bone loss.
----A Aerodiol with its new mode of action--pulsed estrogen therapy made possible by a unique pharmacokinetic profile and an innovative route of administration--acts on the full range of climacteric symptoms and on the long-term consequences of estrogen deprivation. Four well-designed, international studies investigating the efficacy of pulsed estrogen therapy on both the short- and long-term consequences of estrogen deprivation were conducted. Climacteric symptoms and their reduction were assessed individually and also using the Kupperman index, which is a weighted score. Aerodiol produced a significant reduction in the Kupperman index and in the occurrence of menopausal symptoms, such as hot flushes and night sweats. This reduction appeared to be significant as early as the second week of treatment. Moreover, Aerodiol remained effective even among highly symptomatic women with more than seven hot flushes per day, and also among smokers. Since it avoids hepatic first-pass metabolism, pulsed estrogen therapy also has a favorable action on the lipid profile, decreasing lipoprotein(a), apolipoprotein B, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Aerodiol is neutral with regard to clotting factors, angiotensinogen and insulin levels. The effect of pulsed estrogen therapy on bone has been assessed in both the short and the long term. Bone turnover, as measured by markers of resorption and formation, was normalized to premenopausal levels after 3 months of treatment at a dose of 300 microg/day. Aerodiol, again at the dose of 300 microg/day, is as effective as a 50-microg/day transdermal patch in increasing bone mineral density (p < 0.001 versus baseline) at the spine and hip after 56 weeks. Finally, data collected during the development of Aerodiol have shown that pulsed estrogen therapy is at least as effective as 2 mg of oral estrogen or 50 microg of transdermal estrogen in relieving climacteric symptoms and preventing postmenopausal bone loss.
----P Journal_Article Review Review__Tutorial 
----M M_Administration__Cutaneous_MeSH M_Administration__Intranasal_MeSH M_Cardiovascular_Diseases_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacokinetics_MeSH Estradiol_pharmacokinetics_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_prevention_&_control_MeSH Hot_Flashes_prevention_&_control_MeSH M_Human_MeSH P_Menopause_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Pulse_Therapy__Drug_MeSH M_Randomized_Controlled_Trials_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12482164
----K E
----T Responsiveness of the Acne-Specific Quality of Life Questionnaire (Acne-QoL) to treatment for acne vulgaris in placebo-controlled clinical trials.
----A The Acne-Specific Quality of Life Questionnaire (Acne-QoL) was developed to measure the impact of facial acne across four dimensions of patient quality of life. The main objective of the current study was to evaluate the responsiveness of this instrument. Secondarily, this study provided an opportunity to extend the developer's psychometric validation. The Acne-QoL was utilized in two randomized, double-blind, placebo-controlled studies of the efficacy of Estrostep (norethindrone acetate/ethinyl estradiol) in the treatment of facial acne; a total of 296 Estrostep and 295 placebo patients were evaluated. The Acne-QoL was completed at the beginning, middle (cycle 3), and end (cycle 6) of the 6-month treatment period. The responsiveness of the Acne-QoL was demonstrated through its ability to detect both small (baseline to mid-study) and moderate (baseline to study end) treatment advantages for Estrostep patients. Confirmatory factor analysis supported the subscale structure, and internal consistency estimates were excellent. Convergent and discriminant validity were supported by correlations between Acne-QoL scores and clinical measures that were both in the direction and relative magnitude hypothesized. Finally, item response theory analyses confirmed that each item is highly related to its subscale's latent construct and that each subscale is sensitive across a broad range of the underlying continuum. The results of this evaluation confirm that the Acne-QoL is responsive, internally consistent, and valid.
----P Journal_Article Validation_Studies 
----M M_Acne_Vulgaris_MeSH S_psychology_MeSH Acne_Vulgaris_psychology_MeSH M_Adolescent_MeSH M_Adult_MeSH M_Comparative_Study_MeSH M_Controlled_Clinical_Trials_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH M_Patient_Participation_MeSH M_Placebos_MeSH M_Psychometrics_MeSH P_Quality_of_Life_MeSH P_Questionnaires_MeSH P_Sickness_Impact_Profile_MeSH M_Support__Non-U_S__Gov't_MeSH M_United_States_MeSH 
****** 12490735
----K E
----T FDA drug approval summaries: fulvestrant.
----A Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
----P Journal_Article 
----M M_Antineoplastic_Agents__Hormonal_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH M_Drug_Approval_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Postmenopause_MeSH M_Randomized_Controlled_Trials_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Survival_Rate_MeSH M_Treatment_Outcome_MeSH M_United_States_MeSH M_United_States_Food_and_Drug_Administration_MeSH 
****** 12497673
----K E
----T Quality of life issues. Potential role for an oral contraceptive containing ethinyl estradiol and drospirenone.
----A The new combined oral contraceptive containing ethinyl estradiol and drospirenone has the potential for improving a woman's quality of life. Drospirenone's antiandrogenic activity, for example, makes it effective in reducing acne and seborrhea. The majority of reproductive-age women suffer from some degree of premenstrual symptomatology. In some cases, these monthly symptoms are severe enough to negatively impact a woman's quality of life. Drospirenone's antimineralocorticoid activity aids in reducing some of the most bothersome symptoms associated with the premenstrual phase of the menstrual cycle.
----P Journal_Article Review Review__Tutorial 
----M M_Acne_Vulgaris_MeSH S_drug_therapy_MeSH Acne_Vulgaris_drug_therapy_MeSH M_Androgen_Antagonists_MeSH M_Androstenes_MeSH S_administration_&_dosage_MeSH Androstenes_administration_&_dosage_MeSH S_therapeutic_use_MeSH Androstenes_therapeutic_use_MeSH P_Contraceptives__Oral__Combined_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Mineralocorticoids_MeSH S_antagonists_&_inhibitors_MeSH Mineralocorticoids_antagonists_&_inhibitors_MeSH M_Premenstrual_Syndrome_MeSH S_drug_therapy_MeSH Premenstrual_Syndrome_drug_therapy_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH P_Quality_of_Life_MeSH M_Randomized_Controlled_Trials_MeSH M_Weight_Gain_MeSH 
****** 12499030
----K E
----T Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral contraceptive.
----A This randomized, double-blind, placebo-controlled exploratory study examined the efficacy and safety of a low-dose oral contraceptive (Mircette), desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled 77 women (age < or =32 years) with primary dysmenorrhea documented for at least four consecutive cycles. Forty participants received DSG/EE&EE and 37 received placebo for four consecutive 28-day cycles. The intensity of menstrual-related distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient diaries were used to assess number of school/work days missed as well as the use of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual pain severity, lower total MDQ scores, and significantly less menstrual cramping. No significant change in bloating, anxiety, loneliness, weight gain, or acne was reported. The DSG/EE&EE formulation shows promise for the treatment of primary dysmenorrhea and was well tolerated by the participants in this study.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Contraceptives__Oral__Synthetic_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Synthetic_administration_&_dosage_MeSH S_adverse_effects_MeSH Contraceptives__Oral__Synthetic_adverse_effects_MeSH M_Desogestrel_MeSH S_administration_&_dosage_MeSH Desogestrel_administration_&_dosage_MeSH S_adverse_effects_MeSH Desogestrel_adverse_effects_MeSH M_Double-Blind_Method_MeSH M_Dysmenorrhea_MeSH S_drug_therapy_MeSH Dysmenorrhea_drug_therapy_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Headache_MeSH S_chemically_induced_MeSH Headache_chemically_induced_MeSH M_Human_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_United_States_MeSH 
****** 12504395
----K E
----T Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial.
----A BACKGROUND: Results of observational studies suggest that hormone replacement therapy (HRT) could reduce the risk of coronary heart disease (CHD), but those of randomised trials do not indicate a lower risk in women who use oestrogen plus progestagen. The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infarction. METHODS: The study was a randomised, blinded, placebo controlled, secondary prevention trial of postmenopausal women, age 50-69 years (n=1017) who had survived a first myocardial infarction. Individuals were recruited from 35 hospitals in England and Wales. Women received either one tablet of oestradiol valerate (2 mg; n=513) or placebo (n=504), daily for 2 years. Primary outcomes were reinfarction or cardiac death, and all-cause mortality. Analyses were by intention-to-treat. Secondary outcomes were uterine bleeding, endometrial cancer, stroke or other embolic events, and fractures. FINDINGS: Frequency of reinfarction or cardiac death did not differ between treatment groups at 24 months (rate ratio 0.99, 95% CI 0.70-1.41, p=0.97). Similarly, the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant (0.79, 0.50-1.27, p=0.34). The relative risk of any death (0.56, 0.23-1.33) and cardiac death (0.33, 0.11-1.01) was lowest at 3 months post-recruitment. INTERPRETATION: Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infarction.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Great_Britain_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Myocardial_Infarction_MeSH S_mortality_MeSH Myocardial_Infarction_mortality_MeSH S_prevention_&_control_MeSH Myocardial_Infarction_prevention_&_control_MeSH M_Patient_Compliance_MeSH M_Postmenopause_MeSH M_Recurrence_MeSH S_prevention_&_control_MeSH Recurrence_prevention_&_control_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12519833
----K E
----T A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate.
----A Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score < or = 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched for demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven subjects completed at least 18 months in the study, and 26 the full 2 yr, with similar numbers dropping out from each group (mainly for personal reasons). In the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at 12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P < 0.002). Differences of lesser statistical magnitude were seen at the femoral neck (between group differences at 2 yr: 2.7%, P = 0.24), Ward's triangle (5.0%, P = 0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Contraceptive_Agents__Female_MeSH S_administration_&_dosage_MeSH Contraceptive_Agents__Female_administration_&_dosage_MeSH S_adverse_effects_MeSH Contraceptive_Agents__Female_adverse_effects_MeSH S_therapeutic_use_MeSH Contraceptive_Agents__Female_therapeutic_use_MeSH M_Delayed-Action_Preparations_MeSH M_Densitometry__X-Ray_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Femur_Neck_MeSH S_metabolism_MeSH Femur_Neck_metabolism_MeSH S_radiography_MeSH Femur_Neck_radiography_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_metabolism_MeSH Lumbar_Vertebrae_metabolism_MeSH S_radiography_MeSH Lumbar_Vertebrae_radiography_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12519869
----K E
----T Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women.
----A To investigate the dependence of LH pulsatility on energy availability (dietary energy intake minus exercise energy expenditure), we measured LH pulsatility after manipulating the energy availability of 29 regularly menstruating, habitually sedentary, young women of normal body composition for 5 d in the early follicular phase. Subjects expended 15 kcal/kg of lean body mass (LBM) per day in supervised exercise at 70% of aerobic capacity while consuming a clinical dietary product to set energy availability at 45 and either 10, 20, or 30 kcal/kg LBM.d in two randomized trials separated by at least 2 months. Blood was sampled daily during treatments and at 10-min intervals for the next 24 h. Samples were assayed for LH, FSH, estradiol (E2), glucose, beta-hydroxybutyrate, insulin, cortisol, GH, IGF-I, IGF-I binding protein (IGFBP)-1, IGFBP-3, leptin, and T3. LH pulsatility was unaffected by an energy availability of 30 kcal/kg LBM.d (P > 0.3), but below this threshold LH pulse frequency decreased, whereas LH pulse amplitude increased (all P < 0.04). This disruption was more extreme in women with short luteal phases (P < 0.01). These incremental effects most closely resembled the effects of energy availability on plasma glucose, beta-hydroxybutyrate, GH, and cortisol and contrasted with the dependencies displayed by the other metabolic hormones (simultaneously P < 0.05). These results demonstrate that LH pulsatility is disrupted only below a threshold of energy availability deep into negative energy balance and suggest priorities for future investigations into the mechanism that mediates the nonlinear dependence of LH pulsatility on energy availability.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Body_Weight_MeSH M_Carbohydrates_MeSH S_metabolism_MeSH Carbohydrates_metabolism_MeSH M_Circadian_Rhythm_MeSH M_Energy_Metabolism_MeSH S_physiology_MeSH Energy_Metabolism_physiology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Luteinizing_Hormone_MeSH S_secretion_MeSH Luteinizing_Hormone_secretion_MeSH M_Menstrual_Cycle_MeSH S_physiology_MeSH Menstrual_Cycle_physiology_MeSH M_Pulsatile_Flow_MeSH M_Sleep_MeSH S_physiology_MeSH Sleep_physiology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Wakefulness_MeSH S_physiology_MeSH Wakefulness_physiology_MeSH 
****** 12521651
----K E
----T Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: a randomized trial.
----A The purpose of this study is to compare bleeding patterns and acceptability of a contraceptive regimen of combined 20 microg ethinyl estradiol/100 microg levonorgestrel taken with and without a hormone-free interval. Thirty-two women desiring oral contraception were randomized to six 28-day cycles (standard group) or 168 days without a pill-free interval (continuous group). Participants kept a daily bleeding calendar documenting bleeding events (none, spotting or required sanitary protection) and side effects (headache, nausea, breast tenderness, depression, premenstrual syndrome and bloating). Primary outcome was number of bleeding days. Secondary outcomes included bleeding days requiring sanitary protection, amenorrhea, patient acceptability of bleeding patterns, method satisfaction and affective side effects. There were no differences in the baseline characteristics of the two groups. Although total bleeding days were fewer in the continuous group (mean = 25.9 vs. 34.9 days), this result did not reach statistical significance. However, women in the continuous group reported significantly fewer bleeding days that required protection (18.4 vs. 33.8 days, p < 0.01), and were more likely to have amenorrhea. Although both groups reported a high level of satisfaction with bleeding patterns and side effect profiles, women in the continuous group reported significantly fewer days of bloating (0.7 vs. 11.1 days, p = 0.04), and menstrual pain (1.9 vs. 13.3 days, p < 0.01). Continuous use of 20 microg ethinyl estradiol/100 microg levonorgestrel is associated with less bleeding requiring protection, and more amenorrhea than standard administration. Taken with or without a hormone-free interval, this oral contraceptive formulation is highly acceptable with regard to bleeding patterns and side effect profile. The continuous group had fewer light and moderate bleeding days, less bloating and menstrual pain. For patients who are seeking these results, this method may be more desirable.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Contraceptives__Oral__Combined_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Combined_administration_&_dosage_MeSH M_Drug_Administration_Schedule_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH M_Menstrual_Cycle_MeSH P_Menstruation_MeSH M_Oregon_MeSH P_Patient_Satisfaction_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12521655
----K E
----T Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women.
----A With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20-27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 microg ethynyl estradiol and 150 microg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Amino_Acids_MeSH S_blood_MeSH Amino_Acids_blood_MeSH M_Bone_Density_MeSH S_genetics_MeSH Bone_Density_genetics_MeSH M_Contraceptives__Oral__Combined_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Combined_administration_&_dosage_MeSH S_pharmacology_MeSH Contraceptives__Oral__Combined_pharmacology_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Genotype_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_administration_&_dosage_MeSH Levonorgestrel_administration_&_dosage_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Polymorphism_(Genetics)_MeSH M_Prospective_Studies_MeSH M_Receptors__Calcitriol_MeSH S_drug_effects_MeSH Receptors__Calcitriol_drug_effects_MeSH S_genetics_MeSH Receptors__Calcitriol_genetics_MeSH M_Reference_Values_MeSH 
****** 12544674
----K I
----T Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebo-controlled study.
----A OBJECTIVE: The aim of this study was to evaluate the effects of a constant-estrogen, intermittent-progestogen hormone replacement regimen (Ortho-Prefest, Ortho-McNeil Pharmaceutical, Raritan, NJ, USA) on menopausal symptoms measured by the Kupperman Index and on quality of life measured by the Menopause Quality of Life-Intervention questionnaire. DESIGN: This was a randomized, double-blind, placebo-controlled multicenter study of 90 days' duration. Nonhysterectomized, postmenopausal women with vasomotor symptoms and at least 6 months' amenorrhea were eligible. On completion of the placebo-controlled portion of the study, participants could elect to receive active treatment for an additional 90 days. RESULTS: The study enrolled 119 participants, 59 and 60 in the Prefest and placebo groups, respectively. A marked reduction of menopausal symptoms, as measured by the Kupperman Index, was observed in the active treatment group compared with the placebo group after 45 days' treatment (mean reduction, 14.8 v 7.2 points, respectively), which was sustained to day 90 (16.8 v 7.8 points; < 0.001). Similarly, greater improvement in quality of life, as measured by the Menopause Quality of Life summary score, was also observed in the active treatment group for the same period (improvement of up to 1.6 points v 0.7 points; < 0.001). The adverse event profile was unremarkable. Of the 114 participants who received the active treatment, 6 withdrew because of adverse events. CONCLUSIONS: The constant-estrogen, intermittent-progestogen regimen was highly effective in relieving menopausal symptoms and in improving quality of life and was well received by the study participants.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Canada_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Ethinyl_Estradiol-Norgestrel_Combination_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol-Norgestrel_Combination_administration_&_dosage_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norgestrel_MeSH S_administration_&_dosage_MeSH Norgestrel_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norgestrel_analogs_&_derivatives_MeSH P_Postmenopause_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12544676
----K E
----T Influence of raloxifene on the efficacy of an estradiol-releasing ring for treating vaginal atrophy in postmenopausal women.
----A OBJECTIVE: To determine the potential interaction of oral raloxifene 60 mg/day on the efficacy of a low-dose, estradiol-releasing vaginal ring used to treat signs and symptoms of vaginal atrophy in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled, parallel treatment trial of raloxifene and placebo with open-label 17beta-estradiol ring. At 10 sites in the United States, 91 postmenopausal women with at least two signs of vaginal atrophy were treated with a 17beta-estradiol ring and randomized to receive concomitant raloxifene 60 mg/day or placebo for 6 months. Efficacy of treatments was evaluated by comparing investigator assessments of genitourinary atrophic signs, vaginal maturation value, and participant assessments of vaginal symptoms at 6 months. Other measures included rate and severity of hot flashes and assessment of sexual function. Uterine safety was assessed by endometrial biopsy and transvaginal ultrasound. RESULTS: In women treated with a 17beta-estradiol ring, both the raloxifene and placebo treatment groups showed improvements in signs and symptoms of vaginal atrophy at 6 months, with no significant differences in degree of improvement between groups. There were no signs of endometrial proliferation in either group.CONCLUSIONS: Concomitant administration of raloxifene does not alter the effects of the 17beta-estradiol ring on alleviating signs and symptoms of genitourinary atrophy in postmenopausal women.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Administration__Oral_MeSH M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Atrophy_MeSH S_drug_therapy_MeSH Atrophy_drug_therapy_MeSH S_pathology_MeSH Atrophy_pathology_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Antagonists_MeSH S_administration_&_dosage_MeSH Estrogen_Antagonists_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogen_Antagonists_pharmacology_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Pessaries_MeSH P_Postmenopause_MeSH M_Questionnaires_MeSH M_Raloxifene_MeSH S_administration_&_dosage_MeSH Raloxifene_administration_&_dosage_MeSH S_pharmacology_MeSH Raloxifene_pharmacology_MeSH M_Severity_of_Illness_Index_MeSH M_Sexuality_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_United_States_MeSH M_Vagina_MeSH S_pathology_MeSH Vagina_pathology_MeSH 
****** 12547489
----K E
----T Response to letter to the editor. regarding "The completeness, validity, and timeliness of AIDS surveillance data".
----A 
----P Comment Letter 
----M M_Acquired_Immunodeficiency_Syndrome_MeSH S_epidemiology_MeSH Acquired_Immunodeficiency_Syndrome_epidemiology_MeSH P_Epidemiologic_Methods_MeSH M_Human_MeSH P_Population_Surveillance_MeSH M_United_States_MeSH S_epidemiology_MeSH United_States_epidemiology_MeSH 
****** 12551861
----K E
----T C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women.
----A BACKGROUND: The metabolic syndrome describes a high-risk population having 3 or more of the following clinical characteristics: upper-body obesity, hypertriglyceridemia, low HDL, hypertension, and abnormal glucose. All of these attributes, however, are associated with increased levels of C-reactive protein (CRP). METHODS AND RESULTS: We evaluated interrelationships between CRP, the metabolic syndrome, and incident cardiovascular events among 14 719 apparently healthy women who were followed up for an 8-year period for myocardial infarction, stroke, coronary revascularization, or cardiovascular death; 24% of the cohort had the metabolic syndrome at study entry. At baseline, median CRP levels for those with 0, 1, 2, 3, 4, or 5 characteristics of the metabolic syndrome were 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, respectively (P(trend) <0.0001). Over the 8-year follow-up, cardiovascular event-free survival rates based on CRP levels above or below 3.0 mg/L were similar to survival rates based on having 3 or more characteristics of the metabolic syndrome. At all levels of severity of the metabolic syndrome, however, CRP added prognostic information on subsequent risk. For example, among those with the metabolic syndrome at study entry, age-adjusted incidence rates of future cardiovascular events were 3.4 and 5.9 per 1000 person-years of exposure for those with baseline CRP levels less than or greater than 3.0 mg/L, respectively. Additive effects for CRP were also observed for those with 4 or 5 characteristics of the metabolic syndrome. The use of different definitions of the metabolic syndrome had minimal impact on these findings. CONCLUSIONS: These prospective data suggest that measurement of CRP adds clinically important prognostic information to the metabolic syndrome.
----P Journal_Article 
----M M_Aged_MeSH M_C-Reactive_Protein_MeSH S_analysis_MeSH C-Reactive_Protein_analysis_MeSH M_Comparative_Study_MeSH M_Disease-Free_Survival_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Heart_Diseases_MeSH S_diagnosis_MeSH Heart_Diseases_diagnosis_MeSH S_epidemiology_MeSH Heart_Diseases_epidemiology_MeSH S_etiology_MeSH Heart_Diseases_etiology_MeSH M_Human_MeSH M_Incidence_MeSH M_Metabolic_Syndrome_X_MeSH S_blood_MeSH Metabolic_Syndrome_X_blood_MeSH S_complications_MeSH Metabolic_Syndrome_X_complications_MeSH S_diagnosis_MeSH Metabolic_Syndrome_X_diagnosis_MeSH M_Middle_Aged_MeSH M_Prevalence_MeSH M_Prognosis_MeSH M_Prospective_Studies_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_United_States_MeSH 
****** 12551862
----K E
----T C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis.
----A BACKGROUND: Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis via effects on monocytes and endothelial cells. The metabolic syndrome is associated with significantly elevated levels of CRP. Plasminogen activator inhibitor-1 (PAI-1), a marker of atherothrombosis, is also elevated in the metabolic syndrome and in diabetes, and endothelial cells are the major source of PAI-1. However, there are no studies examining the effect of CRP on PAI-1 in human aortic endothelial cells (HAECs). METHODS AND RESULTS: Incubation of HAECs with CRP results in a time- and dose-dependent increase in secreted PAI-1 antigen, PAI-1 activity, intracellular PAI-1 protein, and PAI-1 mRNA. CRP stabilizes PAI-1 mRNA. Inhibitors of endothelial NO synthase, blocking antibodies to interleukin-6 and an endothelin-1 receptor blocker, fail to attenuate the effect of CRP on PAI-1. CRP additionally increased PAI-1 under hyperglycemic conditions. CONCLUSIONS: This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis.
----P Journal_Article 
----M M_Aorta_MeSH S_cytology_MeSH Aorta_cytology_MeSH M_Arteriosclerosis_MeSH S_etiology_MeSH Arteriosclerosis_etiology_MeSH M_C-Reactive_Protein_MeSH S_pharmacology_MeSH C-Reactive_Protein_pharmacology_MeSH M_Cells__Cultured_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH S_metabolism_MeSH Endothelium__Vascular_metabolism_MeSH M_Human_MeSH M_Metabolic_Syndrome_X_MeSH S_etiology_MeSH Metabolic_Syndrome_X_etiology_MeSH M_Plasminogen_Activator_Inhibitor_1_MeSH S_biosynthesis_MeSH Plasminogen_Activator_Inhibitor_1_biosynthesis_MeSH S_genetics_MeSH Plasminogen_Activator_Inhibitor_1_genetics_MeSH S_metabolism_MeSH Plasminogen_Activator_Inhibitor_1_metabolism_MeSH M_RNA_Stability_MeSH M_RNA__Messenger_MeSH S_biosynthesis_MeSH RNA__Messenger_biosynthesis_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Thrombosis_MeSH S_etiology_MeSH Thrombosis_etiology_MeSH 
****** 12559482
----K E
----T Sexual diergism of baseline plasma leptin and leptin suppression by arginine vasopressin in major depressives and matched controls.
----A Leptin inhibits appetite by activating several neuroendocrine systems, including the hypothalamo-pituitary-adrenal cortical (HPA) axis. In turn, chronically elevated glucocorticoids increase circulating leptin. HPA axis hyperactivity occurs in 30-50% of patients with major depression, but the few prior reports of leptin measurements in this illness have shown inconsistent results. We, therefore, measured plasma leptin in 12 female and 8 male unipolar major depressives and 12 female and 8 male individually matched normal controls administered low-dose physostigmine (PHYSO) and arginine vasopressin (AVP) to stimulate the HPA axis. The subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV); AVP (0-08 U/kg IM); PHYSO+AVP; and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for leptin, ACTH(1-39), cortisol and AVP. Estradiol and testosterone also were measured at each test session. PHYSO and AVP produced no side effects in approximately half the subjects and predominantly mild side effects in the other half, with no significant patient-control differences. Correlations between side effects (absent or present) after PHYSO or AVP and the corresponding leptin responses were non-significant in all groups. Baseline plasma leptin concentrations (mean+/-S.D.) were significantly higher in the female patients compared to the female controls (22.5+/-13.9 ng/ml vs. 12.3+/-9.7 ng/ml), whereas they were similar in the male patients and the male controls (3.9+/-1.4 ng/ml vs. 3.6+/-2.0 ng/ml). Leptin concentrations following PHYSO remained unchanged from baseline, indicating that the short-lived ACTH and cortisol increases produced by PHYSO did not affect leptin secretion. In contrast, AVP administration, while also increasing ACTH and cortisol, significantly suppressed leptin, more so in the women than in the men. Baseline leptin and the leptin decrease after AVP were moderately positively correlated with the Hamilton Depression Scale 'somatization' factor in the female patients (r=0.50) and more strongly correlated with the 'mood-depression' factor in the male patients (r=0.81). These findings indicate a sexual diergism (functional sex difference) in plasma leptin measures between major depressives and matched normal controls.
----P Journal_Article 
----M M_Adult_MeSH M_Argipressin_MeSH S_administration_&_dosage_MeSH Argipressin_administration_&_dosage_MeSH S_blood_MeSH Argipressin_blood_MeSH S_pharmacology_MeSH Argipressin_pharmacology_MeSH M_Body_Mass_Index_MeSH M_Cholinesterase_Inhibitors_MeSH S_administration_&_dosage_MeSH Cholinesterase_Inhibitors_administration_&_dosage_MeSH S_pharmacology_MeSH Cholinesterase_Inhibitors_pharmacology_MeSH M_Corticotropin_MeSH S_blood_MeSH Corticotropin_blood_MeSH M_Depression__Involutional_MeSH S_blood_MeSH Depression__Involutional_blood_MeSH M_Female_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH M_Hypothalamo-Hypophyseal_System_MeSH S_drug_effects_MeSH Hypothalamo-Hypophyseal_System_drug_effects_MeSH S_metabolism_MeSH Hypothalamo-Hypophyseal_System_metabolism_MeSH M_Leptin_MeSH S_antagonists_&_inhibitors_MeSH Leptin_antagonists_&_inhibitors_MeSH S_blood_MeSH Leptin_blood_MeSH M_Male_MeSH M_Physostigmine_MeSH S_administration_&_dosage_MeSH Physostigmine_administration_&_dosage_MeSH S_pharmacology_MeSH Physostigmine_pharmacology_MeSH M_Pituitary-Adrenal_System_MeSH S_drug_effects_MeSH Pituitary-Adrenal_System_drug_effects_MeSH S_metabolism_MeSH Pituitary-Adrenal_System_metabolism_MeSH M_Sex_Factors_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH M_Time_Factors_MeSH M_Vasoconstrictor_Agents_MeSH S_administration_&_dosage_MeSH Vasoconstrictor_Agents_administration_&_dosage_MeSH S_pharmacology_MeSH Vasoconstrictor_Agents_pharmacology_MeSH 
****** 12569270
----K E
----T Acute effects of transdermal estrogen on hemodynamic and vascular reactivity in elderly postmenopausal healthy women.
----A OBJECTIVE: The acute effects of estrogen on hemodynamic responses were studied with emphasis on the sympathoadrenal system and peripheral circulation. DESIGN: Eleven healthy postmenopausal women recruited from the population-based study BEDA were included in this randomized, double-blind, cross-over, placebo-controlled hypothesis-generating pilot study, where the effect of transdermal estrogen (17 beta-estradiol, 100 microg/24 h) was tested. METHODS: Twenty-four hours after the patch with estrogen/placebo was attached, the blood pressure during rest and mental stress test was measured, together with blood samples for analysis of P-adrenaline and P-noradrenaline. Twenty-four-hour ambulatory registration of blood pressure and heart rate were recorded. Contractile properties and endothelial function of subcutaneous small arteries from gluteal biopsies were studied with the wire-myograph technique. RESULTS: Estrogen treatment reduced both ambulatory systolic blood pressure (5 mmHg, P = 0.05), diastolic blood pressure (3 mmHg, P < 0.05) and heart rate (6-8 beats/min during morning hours, P < 0.01). Diastolic blood pressure during and after mental stress was significantly reduced after estrogen treatment (p < 0.01). The levels of P-adrenaline and P-noradrenaline were similar in both treatment protocols. The contractile properties of the arteries were not significantly influenced by estrogen. Substance P induced nitric oxide-dependent relaxation in both estrogen-treated and placebo-treated precontracted arteries. Acetylcholine, on the other hand, induced a non-nitric oxide, non-prostanoid-dependent hyperpolarization, which was inhibited by potassium-induced depolarization after placebo but not after estrogen treatment. CONCLUSIONS: Acute administration of transdermal estrogen in clinically relevant doses modulates hemodynamics, probably by an altered parasympathetic balance, which might involve changes at the muscarinic receptor level.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Arteries_MeSH S_physiology_MeSH Arteries_physiology_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH S_physiology_MeSH Endothelium__Vascular_physiology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Heart_Rate_MeSH S_drug_effects_MeSH Heart_Rate_drug_effects_MeSH M_Hemodynamic_Processes_MeSH S_drug_effects_MeSH Hemodynamic_Processes_drug_effects_MeSH M_Human_MeSH M_Pilot_Projects_MeSH P_Postmenopause_MeSH S_blood_MeSH Postmenopause_blood_MeSH M_Reference_Values_MeSH M_Skin_MeSH S_blood_supply_MeSH Skin_blood_supply_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vasoconstriction_MeSH S_drug_effects_MeSH Vasoconstriction_drug_effects_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH 
****** 12568736
----K E
----T A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms.
----A OBJECTIVES: Interest in use of alternative remedies for managing menopausal symptoms is increasing exponentially during these years. Jia-Wey Shiau-Yau San (JWSYS), one of the traditional Chinese herbal prescriptions, is a famous herbal remedy used for the management of various menopausal-related symptoms. A randomized, controlled pilot study was performed to evaluate the clinical effects of JWSYS compared with those of a continuous combined hormone replacement therapy, Premelle, on quality of life in non-hysterectomized postmenopausal women. METHODS: The present trial compared the effect of a l6-week treatment with JWSYS or HRT (Premelle) in postmenopausal women with climacteric symptoms. The Greene Climacteric Scale was used to assess the clinical effects at baseline and after 16 weeks' treatment with either JWSYS or Premelle. The physiological parameters, such as follicle-stimulating hormone and estradiol levels, were also recorded at the same time points. RESULTS: The results showed that JWSYS had a relatively lower discontinuation rate due to adverse effects, in particular the bleeding and breast tenderness. Both JWSYS and Premelle effectively alleviated most of the menopausal symptoms with no significant differences between treatment groups, whereas the beneficial effects of JWSYS were not mediated by hormone replacement-like effects. Moreover, JWSYS showed a good compliance and safety without estrogenic effects and metabolic alterations. CONCLUSIONS: It was suggested that JWSYS was a safe and efficacious therapy and might be an alternative choice for relief of climacteric symptoms in postmenopausal women. However, the exact efficacy and clinical roles of JWSYS have not been convincingly demonstrated in this study because of the blinding approach and some statistical concerns, and only the possibility of its efficacy has been raised. Therefore, a blinding trial with more patient numbers to evaluate the efficacy of JWSYS deserves further study.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Climacteric_MeSH S_drug_effects_MeSH Climacteric_drug_effects_MeSH M_Drugs__Chinese_Herbal_MeSH S_therapeutic_use_MeSH Drugs__Chinese_Herbal_therapeutic_use_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Pilot_Projects_MeSH P_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12571667
----K E
----T A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.
----A OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Body_Height_MeSH S_drug_effects_MeSH Body_Height_drug_effects_MeSH M_Body_Weight_MeSH S_drug_effects_MeSH Body_Weight_drug_effects_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH P_Dietary_Supplements_MeSH M_Estrogens__Non-Steroidal_MeSH S_pharmacology_MeSH Estrogens__Non-Steroidal_pharmacology_MeSH M_Human_MeSH P_Isoflavones_MeSH M_Male_MeSH M_Plant_Preparations_MeSH M_Support__Non-U_S__Gov't_MeSH M_Tasmania_MeSH M_Time_Factors_MeSH 
****** 12573305
----K E
----T On the role of menopause for sleep-endocrine alterations associated with major depression.
----A Aging and menopause are associated with alterations of the sleep EEG, while age-related changes of the hypothalamo-pituitary-adrenal (HPA) axis remain controversial. Major depression is also associated with typical sleep-endocrine changes, including enhanced activity of the HPA axis, while an influence of age and gender on these alterations is less clear. To test the hypothesis that after menopause sleep-endocrine alterations associated with major depression are accentuated, we examined the sleep EEG and nocturnal hormone secretion (ACTH, cortisol, GH, estradiol, LH, FSH, and leptin) in 16 drug-free female patients, mostly with the first episode of a major depressive disorder (seven pre- and nine postmenopausal subjects) and 19 female controls (10 subjects in the early follicular phase and nine postmenopausal subjects).Nocturnal cortisol secretion was increased in postmenopausal patients with depression, while a decrease was noted in postmenopausal controls. Sleep alterations typically associated with depression, namely a reduction in sleep continuity and slow wave sleep (SWS) and an increase in REM density, were prominent in post- but not in premenopausal patients. An inverse correlation was noted between the decline in SWS and sleep continuity and FSH secretion in patients with depression, suggesting a role of menopause for these sleep-endocrine alterations typically associated with major depression. In contrast, in premenopausal patients we noted primarily a shift in SWS and delta-EEG activity from the first to the second non-REM period, which was not related to age or hormone secretion.Though the relatively small number of subjects per group precludes a definitive conclusion, our data open up the possibility that the sleep-endocrine changes typically associated with major depression are most prominent in postmenopausal patients. Whether the predominant alteration of the distribution of SWS and delta EEG activity in younger patients with a first episode of major depression has a predictive value for the future course of the disease remains to be investigated.
----P Clinical_Trial Controlled_Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Aged_MeSH M_Comparative_Study_MeSH M_Corticotropin_MeSH S_blood_MeSH Corticotropin_blood_MeSH M_Depression__Involutional_MeSH S_complications_MeSH Depression__Involutional_complications_MeSH S_physiopathology_MeSH Depression__Involutional_physiopathology_MeSH M_Electroencephalography_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Human_Growth_Hormone_MeSH S_blood_MeSH Human_Growth_Hormone_blood_MeSH M_Hydrocortisone_MeSH S_blood_MeSH Hydrocortisone_blood_MeSH M_Leptin_MeSH S_blood_MeSH Leptin_blood_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Matched-Pair_Analysis_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Pituitary_Hormones__Anterior_MeSH S_blood_MeSH Pituitary_Hormones__Anterior_blood_MeSH M_Polysomnography_MeSH M_Sleep_Disorders_MeSH S_complications_MeSH Sleep_Disorders_complications_MeSH S_physiopathology_MeSH Sleep_Disorders_physiopathology_MeSH M_Sleep__REM_MeSH S_physiology_MeSH Sleep__REM_physiology_MeSH M_Statistics_MeSH 
****** 12573306
----K E
----T Effects of hormone replacement therapy on perceptual and cognitive event-related potentials in menopausal insomnia.
----A The influence of a combined estrogen-progestin regimen (Climodien, Lafamme) on auditory event-related potentials (ERPs) was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3=estradiol valerate 2 mg+the progestin dienogest 3 mg, EV=estradiol valerate 2 mg, and placebo), followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg+dienogest 2 mg). Both the double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone odd-ball paradigm in 49 patients aged between 46 and 67 yr with the diagnosis of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1). Climodien reduced standard N1 and target P300 latencies as compared to placebo, while EV did not affect N1 latency but similarly reduced P300 latency. Climodien increased N1, P2 and P300 amplitudes dose-dependently, predominantly at frontal leads. Estrogen alone had only minor effects on ERP amplitudes. The shortening of standard N1 latency and enhancement of N1 and P2 amplitudes indicates a positive effect of Climodien on perceptual processing, most likely due to vigilance improvements also observed in EEG mapping. Concerning target P300, it seems that estradiol is responsible for the improvement in stimulus evaluation time, as reflected by the shortening of the peak latency, while dienogest seems to account for the improvement in cognitive information processing capacity, whereby 3 mg induced a more pronounced augmentation of P300 amplitudes than 2 mg. Based on the spatial distribution of this increase, it can be speculated that Climodien mainly affects the more frontally distributed P3a subcomponent, which is associated with attention and orientation. Furthermore, the observed changes in ERP-components are consistent with recent studies showing significant positive effects of hormone replacement therapy on cholinergic functions. Thus, Climodien seems to be of interest in preventing cognitive decline and treating cognitive disorders in postmenopausal women. Indeed, there is increasing evidence of beneficial effects of estrogen in dementia. Our present findings suggest that the estrogen effects may be augmented by dienogest.
----P Clinical_Trial Clinical_Trial__Phase_III Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH M_Aged_MeSH M_Comparative_Study_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Electrophysiology_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Event-Related_Potentials__P300_MeSH S_drug_effects_MeSH Event-Related_Potentials__P300_drug_effects_MeSH M_Evoked_Potentials__Auditory_MeSH S_drug_effects_MeSH Evoked_Potentials__Auditory_drug_effects_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Nandrolone_MeSH S_administration_&_dosage_MeSH Nandrolone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Nandrolone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Nandrolone_pharmacology_MeSH M_Neuropsychological_Tests_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_pharmacology_MeSH Progesterone_Congeners_pharmacology_MeSH M_Reaction_Time_MeSH M_Sleep_Initiation_and_Maintenance_Disorders_MeSH S_physiopathology_MeSH Sleep_Initiation_and_Maintenance_Disorders_physiopathology_MeSH 
****** 12580705
----K E
----T Estrogen levels do not correlate with improvement in cognition.
----A OBJECTIVE: To investigate whether an association exists between estradiol and estrone levels and measures of cognitive functioning in women with Alzheimer disease (AD) treated with conjugated equine estrogen (Premarin; Wyeth-Ayerst, Philadelphia, Pa). METHODS: We studied 120 postmenopausal women who underwent hysterectomy and who had AD treated with Premarin for 1 year. Plasma estradiol and estrone levels were determined at multiple points during the 1-year treatment trial. The change from baseline level at 2 and 12 months was associated with the change score on 7 different assessments of cognitive functioning. RESULTS: At baseline, estradiol levels were low and there were no associations between the estradiol level and the 7 neuropsychological measures. A similar pattern was observed for estrone treatment. During treatment with 0.625 mg/d of Premarin, estradiol levels increased about 4-fold; while receiving 1.25 mg/d of Premarin, estradiol levels increased about 8-fold. A similar pattern was seen with estrone treatment. For both estradiol and estrone levels, there were no significant associations between the change in plasma level and the change in neuropsychological test scores at either 2 or 12 months. CONCLUSION: Although Premarin elevated estradiol and estrone levels, there was no association between hormone levels and cognitive functioning after either 2 or 12 months of treatment.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Alzheimer_Disease_MeSH S_complications_MeSH Alzheimer_Disease_complications_MeSH S_drug_therapy_MeSH Alzheimer_Disease_drug_therapy_MeSH S_physiopathology_MeSH Alzheimer_Disease_physiopathology_MeSH M_Cognition_Disorders_MeSH S_drug_therapy_MeSH Cognition_Disorders_drug_therapy_MeSH S_etiology_MeSH Cognition_Disorders_etiology_MeSH S_physiopathology_MeSH Cognition_Disorders_physiopathology_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Estrone_MeSH S_blood_MeSH Estrone_blood_MeSH S_pharmacology_MeSH Estrone_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Postmenopause_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12581627
----K E
----T Role of androgens in mild cognitive impairment and possible interventions during andropause.
----A Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.
----P Journal_Article 
----M P_Aging_MeSH M_Androgens_MeSH S_physiology_MeSH Androgens_physiology_MeSH M_Cognition_Disorders_MeSH S_etiology_MeSH Cognition_Disorders_etiology_MeSH S_therapy_MeSH Cognition_Disorders_therapy_MeSH M_Hormones_MeSH S_therapeutic_use_MeSH Hormones_therapeutic_use_MeSH M_Human_MeSH M_Male_MeSH P_Memory_MeSH M_Memory_Disorders_MeSH S_etiology_MeSH Memory_Disorders_etiology_MeSH S_therapy_MeSH Memory_Disorders_therapy_MeSH M_Models__Theoretical_MeSH M_Tomography__Emission-Computed_MeSH 
****** 12590012
----K I
----T Effects of low-dose, continuous combined estradiol and noretisterone acetate on menopausal quality of life in early postmenopausal women.
----A OBJECTIVES: To describe the effects of low dose hormonal replacement therapy (LD-HRT) on quality of life in early postmenopausal women, since the postmenopausal estrogen deprivation in mid age women often brings along a series of changes and symptoms, which may greatly affect quality of life. METHODS: Fifty normal postmenopausal women were recruited and randomly treated with LD-HRT, 17beta-estradiol (1 mg/day) and norethisterone acetate (0.5 mg/day) (LD-HRT) or calcium supplement (controls). No significant differences in age, age at menopause, the presence of chronic diseases and socio-economic status were present in the two groups. The Women's Health Questionnaire (WHQ), a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and after 6 and 12 weeks of treatment in both groups. RESULTS: At baseline no significant differences in WHQ scores were present in the two groups. In the control group the scores in all different areas showed no significant modification either after 6 and 12 weeks of observation. Conversely, the LD-HRT group showed a significant decrease in the scores of vasomotor symptoms, somatic symptoms, anxiety/fear, depressed mood and sleep problem items. No effects on memory/concentration and menstrual symptoms areas were evident. CONCLUSION: Although quality of life is also and may be mainly influenced by socio-economic and cultural factors, LD-HRT definitively can improve not only vasomotor symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_psychology_MeSH Menopause_psychology_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH P_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Treatment_Outcome_MeSH 
****** 12603185
----K E
----T Computerised reminders and feedback in medication management: a systematic review of randomised controlled trials.
----A OBJECTIVE: To systematically review randomised controlled trials (RCTs) of computer-generated medication reminders or feedback directed to healthcare providers or patients. DATA SOURCES: Extensive computerised and manual literature searches identified 76 English-language reports of RCTs reported before 1 January 2002. Searches were conducted between June 1998 and April 2002. STUDY SELECTION: 26 papers making 29 comparisons (two papers reported on multiple interventions) of computer-supported medication management to a control group. DATA EXTRACTION: The quality of the RCTs was systematically assessed and scored independently by two reviewers. Rates of compliance with (potential) reminders for the control and intervention groups were extracted. DATA SYNTHESIS: Heterogeneity of studies prevented a meta-analysis. Where possible, rates were calculated using the intention-to-treat principle. The comparisons were grouped into five areas. Reminders to providers in outpatient settings: six of 12 comparisons demonstrated positive effects (relative rates [RRs: intervention rates/control rates], 1.0 to 42.0). Provider feedback in outpatient settings: five of seven comparisons showed improved clinician behaviour (RRs, 1.0 to 2.5). Combined reminders and feedback in outpatient settings: the single comparison found no improvement. Reminders to providers in inpatient settings: three of five comparisons showed improvements (RRs, 1.0 to 2.1). Patient-directed reminders: two of four comparisons showed improvements in patient compliance. CONCLUSION: Reminders are more effective than feedback in modifying physician behaviour related to medication management. Patient-directed reminders can improve medication adherence.
----P Journal_Article Review Review__Tutorial 
----M P_Drug_Therapy_MeSH P_Feedback_MeSH M_Human_MeSH M_Outpatients_MeSH M_Patient_Compliance_MeSH M_Physician's_Practice_Patterns_MeSH S_statistics_&_numerical_data_MeSH Physician's_Practice_Patterns_statistics_&_numerical_data_MeSH M_Quality_Control_MeSH M_Randomized_Controlled_Trials_MeSH P_Reminder_Systems_MeSH 
****** 12611754
----K E
----T 17beta-estradiol reduces plasma Abeta40 for HRT-naive postmenopausal women with Alzheimer disease: a preliminary study.
----A OBJECTIVE: One mechanism to support the potentially beneficial effects of estrogen in the brain for postmenopausal women potentially involves the hormone's ability to favorably alter the processing of amyloid-precursor protein (APP), believed to play an important role in the pathobiology of Alzheimer disease (AD). The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Abeta40, for postmenopausal women with AD. METHODS: In a placebo-controlled, double blind, parallel-group design study, 20 women were randomized to receive either 0.10 mg/day of transdermal 17beta-estradiol or a placebo for 8 weeks and were retrospectively evaluated as to whether basal levels of Abeta40 were affected by pre-study use of hormone replacement therapy (HRT). Blood samples were collected and cognitive tests were administered at baseline; at Weeks 3, 5, and 8 during treatment; and again 8 weeks after treatment termination. RESULTS: For the group as a whole, plasma Abeta40 was not reliably reduced in response to short-term estradiol administration. For HRT-naive subjects, baseline Abeta40 concentrations were higher than those of previous HRT users, and controlled estradiol administration significantly reduced plasma Abeta40 by the end of the 8-week treatment period. CONCLUSIONS: These results provide preliminary clinical evidence to support an effect of estradiol on Abeta-processing for AD women who are HRT-naive. This finding suggests that the hormone may serve as an Abeta-lowering agent for HRT-naive AD women, which may, in turn, have ultimate ramifications for the progression of AD pathology.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alzheimer_Disease_MeSH S_diagnosis_MeSH Alzheimer_Disease_diagnosis_MeSH S_metabolism_MeSH Alzheimer_Disease_metabolism_MeSH M_Amyloid_beta-Protein_MeSH S_blood_MeSH Amyloid_beta-Protein_blood_MeSH S_metabolism_MeSH Amyloid_beta-Protein_metabolism_MeSH M_Brain_MeSH S_metabolism_MeSH Brain_metabolism_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Peptide_Fragments_MeSH S_blood_MeSH Peptide_Fragments_blood_MeSH S_metabolism_MeSH Peptide_Fragments_metabolism_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Retrospective_Studies_MeSH M_Severity_of_Illness_Index_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH 
****** 12619737
----K E
----T Hormone replacement therapy: the final frontier.
----A 
----P Comment Journal_Article 
----M 
****** 12622925
----K E
----T Percutaneous estrogen in prevention of early postmenopausal bone loss in Chinese women.
----A OBJECTIVE: To identify the optimal dosage of 17beta-estradiol gel + oral progestin for preventing bone loss in postmenopausal Chinese women. METHODS: A 3-year open label, randomized, prospective clinical trial was conducted. Sixty healthy women who had been postmenopausal for 1 to 5 years were recruited and divided into following 4 groups: group 1, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus micronized progesterone (MP) 100 mg/d; group 2, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d; group 3, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus micronized progesterone (MP) 100 mg/d; and group 4, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d. Estrogen and progestin were given continuously for 25 days per month. Bone mineral density (BMD) was measured using quantitative computed tomography (QCT) for trabecular bone of L2-5 and dual energy X-ray absorptiometry (DEXA) for L2-4 and hip 5 times during the trial at baseline and at the 6-, 12-, 18-, 24- and 36-month visits. RESULTS: Fifty-nine patients (98.3%, 59/60) stayed in the study for 1 year, 56 patients (93.3%, 56/60) for 2 years, and 51 (85%, 51/50) for 3 years. On average, menopausal symptoms were relieved by 80% after 6 months of treatment. By the 24th month, the mean increase in BMD ranged from 4.3% to 7.5% in trabecular bone; and by the 36th month, it ranged from 4.2% to 6.2% in L2-4 and 1.61% to 3.77% in the neck. There were significant difference after treatment (P < 0.05). Among the four groups, no significant difference (P > 0.05) was found in improvement of symptoms, levels of bone markers or BMD. CONCLUSION: A daily dose of estradiol gel, either 0.75 mg or 1.5 mg, is effective in preventing early postmenopausal bone loss and relieving menopausal symptoms. After 3-year treatment, spinal BMD could increase steadily, so does hip BMD, especially in the first 2 years.
----P Journal_Article 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Bone_Density_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Fractures_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH 
****** 12626212
----K I
----T Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women.
----A The largest-to-date randomized trial (Women's Health Initiative) comparing the effects of hormone replacement therapy (HRT) and a placebo concluded that the continuous use of an oral combination of conjugated equine estrogens (CEE) and medroxy-progesterone acetate (MPA) increases the risk of breast cancer. This conclusion may not apply to women taking other estrogen and progestin formulations, as suggested by discrepancies in the findings of in vitro studies, epidemiological surveys and, mostly, in vivo studies of human breast epithelial cell proliferation showing opposite effects of HRT combining CEE plus MPA or estradiol plus progesterone. To evaluate the risk of breast cancer associated with the use of the latter combination, commonly prescribed in France, a cohort including 3175 postmenopausal women was followed for a mean of 8.9 years (28 367 woman-years). In total, 1739 (55%) of these women were users of one type of estrogen replacement with systemic effect during at least 12 months, any time after the menopause, and were classified as HRT users. Among them, 83% were receiving exclusively or mostly a combination of a transdermal estradiol gel and a progestin other than MPA. Some 105 cases of breast cancer occurred during the follow-up period, corresponding to a mean of 37 new cases per 10 000 women/year. Using multivariate analysis adjusted for the calendar period of treatment, date of birth and age at menopause, we were unable to detect an increase in the relative risk (RR) of breast cancer (RR 0.98, 95% confidence interval (CI): 0.65-1.5) in the HRT users. The RR of breast cancer per year of use of HRT was 1.005 (95% CI 0.97-1.05). These results do not justify early interruption of such a type of HRT, which is beneficial for quality of life, prevention of bone loss and cardiovascular risk profile, without the activation of coagulation and inflammatory protein synthesis measured in users of oral estrogens.
----P Journal_Article 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Adult_MeSH M_Breast_Neoplasms_MeSH S_epidemiology_MeSH Breast_Neoplasms_epidemiology_MeSH M_Cohort_Studies_MeSH M_Comparative_Study_MeSH M_Confidence_Intervals_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_France_MeSH S_epidemiology_MeSH France_epidemiology_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Multivariate_Analysis_MeSH M_Postmenopause_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH M_Proportional_Hazards_Models_MeSH M_Questionnaires_MeSH M_Registries_MeSH M_Risk_Assessment_MeSH M_Support__Non-U_S__Gov't_MeSH M_Time_Factors_MeSH 
****** 12626213
----K E
----T Differing effects of low-dose estrogen-progestin therapy and pravastatin in postmenopausal hypercholesterolemic women.
----A BACKGROUND: Most studies examining the potential cardioprotective effects of postmenopausal estrogen have been undertaken in healthy women, with doses that may not be appropriate for long-term intervention. New low-dose estrogen-progestin regimens alleviate postmenopausal symptoms with a favorable side-effect profile; however, little is known of the impact of such regimens in women at increased risk of cardiovascular disease. Hence, we have evaluated the effects of low-dose oral estrogen-progestin therapy on serum lipoprotein lipids, brachial artery reactivity and fibrinogen in hypercholesterolemic postmenopausal women in direct comparison with the effects of pravastatin, a lipid-lowering agent known to reduce cardiovascular events in women. METHODS: In a randomized, double-blind, double-dummy, parallel trial, we studied the effects of continuous combined estrogen-progestin therapy (1 mg 17beta-estradiol with 500 micro g norethisterone acetate daily) or pravastatin (20 mg daily) in 72 postmenopausal women with fasting serum low-density lipoprotein (LDL) cholesterol levels greater than 124 mg/dl after an 8-week run-in diet, over a 24-week period. The primary end-point was percentage change in LDL cholesterol from baseline. RESULTS: The intention-to-treat population comprised 65 women, mean age 59 +/- 6.3 years, and 29 in each group completed the trial. Diet alone reduced LDL cholesterol significantly in both treatment groups, in association with a reduction in weight during this period. Compared with respective baseline values, pravastatin decreased LDL cholesterol and total cholesterol to a greater extent than hormone therapy (p = 0.0001 and 0.003 for difference between treatments, respectively). High-density lipoprotein (HDL) cholesterol levels decreased with hormone therapy, but did not change with pravastatin (p = 0.01). Lipoprotein(a) decreased significantly with hormone therapy only (-14%, 95% confidence interval (CI) -21 to -6%, p = 0.01 for difference between groups). Brachial artery flow-mediated dilatation (FMD) was impaired at baseline, and this increased with hormone therapy (absolute mean change in artery diameter as percentage units 2.07, 95% CI 0.57-3.57, p = 0.009) versus no change with pravastatin (0.19, 95% CI -1.1 to 1.5, p = 0.78), with a near-significant difference between the two groups (p = 0.058). A significant correlation between improved brachial artery FMD and reduction in LDL cholesterol was not observed. Fibrinogen decreased significantly in both treatment groups with no difference between treatments. CONCLUSIONS: In postmenopausal hypercholesterolemic women, pravastatin and hormone therapy exhibited divergent effects. The former lowered total and LDL cholesterol more effectively, whereas hormone therapy lowered lipoprotein(a) significantly and improved brachial artery endothelium-dependent dilatation, independent of the reduction in LDL cholesterol. The modest increase in brachial artery FMD seen is consistent with hypercholesterolemia compromising endothelial integrity, and suggests that the important effect of estrogen on the endothelial microenvironment may be attenuated in women with endothelial dysfunction.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Anticholesteremic_Agents_MeSH S_administration_&_dosage_MeSH Anticholesteremic_Agents_administration_&_dosage_MeSH M_Brachial_Artery_MeSH S_drug_effects_MeSH Brachial_Artery_drug_effects_MeSH M_Diet__Reducing_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Fibrinogen_MeSH S_analysis_MeSH Fibrinogen_analysis_MeSH M_Human_MeSH M_Hypercholesterolemia_MeSH S_blood_MeSH Hypercholesterolemia_blood_MeSH S_physiopathology_MeSH Hypercholesterolemia_physiopathology_MeSH S_therapy_MeSH Hypercholesterolemia_therapy_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH S_drug_effects_MeSH Lipoproteins__HDL_Cholesterol_drug_effects_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH S_drug_effects_MeSH Lipoproteins__LDL_Cholesterol_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_adverse_effects_MeSH Norethindrone_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH P_Postmenopause_MeSH M_Pravastatin_MeSH S_administration_&_dosage_MeSH Pravastatin_administration_&_dosage_MeSH M_Progesterone_Congeners_MeSH S_administration_&_dosage_MeSH Progesterone_Congeners_administration_&_dosage_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH M_Quality_of_Life_MeSH M_Reference_Values_MeSH M_Regional_Blood_Flow_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12626086
----K E
----T Vaginal estrogen preparations: a review of safety and efficacy for vaginal atrophy.
----A BACKGROUND: A theoretical advantage of local (i.e., vaginal) therapy of genitourinary symptoms could be avoidance of systemic adverse effects. Review of efficacy and adverse effects of commonly prescribed vaginal estrogens is of great clinical relevance. METHODS: A Medline (1966-present) search was performed for randomized controlled trials involving vaginal estrogens. Reference lists of papers were reviewed for additional references. RESULTS: Twenty-two references were randomized controlled trials of vaginal estrogens used by postmenopausal women with signs or symptoms of vaginal atrophy. Subject numbers ranged from 20 to 251. Duration ranged from 2 weeks to 1 year. Different preparations and schedules were used across the trials. All treatments alleviated signs and symptoms of atrophic vaginitis, regardless of whether objective signs of atrophy were required for study entry. Data for urinary symptoms was conflicting; the ring may prevent recurrent urinary tract infections (UTIs). The trials with endometrial scrutiny were less than one year and had mixed results. Nonhormonal lubricant is effective in improving some atrophic signs and symptoms. All preparations were associated with vaginal irritation. Bleeding with vaginal estradiol tablets may be less than that with CEE cream. Vaginal tablets or rings were preferred over other preparations. There were no serious adverse events reported. There was occasional expulsion of estradiol ring in the setting of prior hysterectomy. CONCLUSIONS: All preparations are effective in decreasing signs and symptoms of vaginal atrophy, but they differ slightly in their adverse event profiles. Long-term safety of the preparations is best established for estradiol tablets (1 year), but is lacking for all preparations.
----P Journal_Article Review Review__Academic 
----M M_Administration__Intravaginal_MeSH M_Atrophy_MeSH S_drug_therapy_MeSH Atrophy_drug_therapy_MeSH P_Drug_Delivery_Systems_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Pessaries_MeSH M_Randomized_Controlled_Trials_MeSH M_Treatment_Outcome_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Creams__Foams_and_Jellies_MeSH S_administration_&_dosage_MeSH Vaginal_Creams__Foams_and_Jellies_administration_&_dosage_MeSH M_Vaginal_Diseases_MeSH S_drug_therapy_MeSH Vaginal_Diseases_drug_therapy_MeSH 
****** 12627040
----K E
----T Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study.
----A OBJECTIVE: To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms (hot flashes and night sweats) in peri- and postmenopausal women. DESIGN: A double-masked, randomized, controlled, clinical trial was conducted. A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were randomized into one of three groups. In all groups, participants consumed a daily supplement containing 25 g of soy protein and were randomly assigned to one of three groups: (a) isoflavone extracted soy protein (control), (b) soy protein with a medium dose of isoflavones (42 mg/day), or (c) soy protein with a higher dose of isoflavones (58 mg/day). The primary outcome measure in this trial was change in reported vasomotor symptoms. RESULTS: A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups. No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone, middle isoflavone, or control groups. The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy. CONCLUSIONS: These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Climacteric_MeSH M_Dietary_Supplements_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Isoflavones_MeSH S_administration_&_dosage_MeSH Isoflavones_administration_&_dosage_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Middle_Aged_MeSH P_Phytotherapy_MeSH M_Postmenopause_MeSH M_Severity_of_Illness_Index_MeSH M_Soybean_Proteins_MeSH S_administration_&_dosage_MeSH Soybean_Proteins_administration_&_dosage_MeSH S_therapeutic_use_MeSH Soybean_Proteins_therapeutic_use_MeSH P_Soybeans_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Treatment_Outcome_MeSH 
****** 12629097
----K E
----T Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: a randomized-controlled study.
----A Administration of recombinant human (rh) IGF-I has been shown to have positive effects on bone density in anorexia nervosa, but the effects of rhIGF-I and estrogen on IGF binding protein (IGFBP)-2 and IGFBP-3 in anorexia nervosa are not known. Sixty-five osteopenic women with anorexia nervosa were randomized to rhIGF-I (30 micro g/kg sc twice daily) alone (n = 15), daily ethinyl estradiol (Ovcon 35) with rhIGF-I (n = 15), estradiol and placebo (n = 15), or placebo (n = 14) for 9 months. Subjects were 25.6 +/- 0.8 yr of age, low weight (body mass index 16.6 +/- 0.2 kg/m(2)) and osteopenic (T scores -2.06 +/- 0.09 for spine and -1.76 +/- 0.13 for hip). IGFBP-3 correlated with total hip bone density (r = 0.47, P = 0.0002) and was a significant predictor of hip bone density (P = 0.010) independent of IGF-I and body mass index in a multivariate regression model. During therapy, IGFBP-2 increased by 48 +/- 19 ng/ml in response to rhIGF-I and decreased by -38 +/- 22 ng/ml in response to placebo (P = 0.011). IGFBP-3 decreased (-895 +/- 120 ng/ml) in response to rhIGF-I but showed a minimal change (-53 +/- 99 ng/ml) in response to placebo (P < 0.0001). In contrast, no significant effect of estrogen was seen on IGF-I, IGFBP-2 or IGFBP-3. Among patients receiving rhIGF-I, the change in IGFBP-2 was inversely associated with the change in total hip bone density (R = -0.47, P = 0.013). In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa. IGFBP-2 and IGFBP-3 may be important determinants of bone density in this population.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Anorexia_Nervosa_MeSH S_drug_therapy_MeSH Anorexia_Nervosa_drug_therapy_MeSH S_metabolism_MeSH Anorexia_Nervosa_metabolism_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_Binding_Protein_3_MeSH S_blood_MeSH Insulin-Like_Growth_Factor_Binding_Protein_3_blood_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_administration_&_dosage_MeSH Insulin-Like_Growth_Factor_I_administration_&_dosage_MeSH S_analysis_MeSH Insulin-Like_Growth_Factor_I_analysis_MeSH M_Insulin-Like_Growth_Factor-Binding_Protein_2_MeSH S_blood_MeSH Insulin-Like_Growth_Factor-Binding_Protein_2_blood_MeSH M_Recombinant_Proteins_MeSH S_administration_&_dosage_MeSH Recombinant_Proteins_administration_&_dosage_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12630067
----K E
----T Measurement of steroid levels in saliva in a population-based survey of lifestyle, medical conditions, marriage, sex life and hormone status in aging men: a feasibility study.
----A Some population-based studies on male aging measure testosterone and cortisol in saliva instead of serum, but very few measure estradiol and dehydroepiandrosterone sulfate (DHEA-S), suggesting further testing is needed for reliability and comparative validity. In addition, the effects of interview stress and circadian hormone secretion need to be checked. In a pilot study on the overall sexual capacity of aging men, 48 randomly selected, healthy, heterosexual, cohabiting men aged 50-80 years, from Mannheim, Germany, and 50 from the State College, Pennsylvania, USA, were administered a standardized interview covering medical biography, present and previous life and work, marriage and emotional status. Two saliva samples were collected from each subject for measurement of testosterone, cortisol, estradiol and DHEA-S levels before and after the interview, and each subject completed a confidential self-administered questionnaire on intercourse, masturbation, orgasm, fantasies, libido and arousal. Questionnaires, hormone measurement techniques and the survey protocol had been extensively pretested. Prior to the pilot study, the kits for measuring testosterone and DHEA-S in saliva were checked for comparative validity against established measuring techniques in serum in 31 cases for testosterone and in 24 different cases for DHEA-S. These 55 cases underwent clinical diagnosis and were not otherwise involved in this study. The cases had been referred to the Andrology Unit of the University Hospital, Marburg, for reasons unrelated to this study. Given the biological differences for both steroids between their presence in blood and in saliva, a perfect correspondence between the two values was not expected and was not observed. The correlations obtained, however, support the assumption that all statistical relationships between testosterone and DHEA-S values in serum and clinical, as well as behavioral, variables reported to date may be replicated for testosterone and DHEA-S values in saliva.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Aging_MeSH S_metabolism_MeSH Aging_metabolism_MeSH M_Anti-Inflammatory_Agents_MeSH S_analysis_MeSH Anti-Inflammatory_Agents_analysis_MeSH M_Dehydroepiandrosterone_Sulfate_MeSH S_analysis_MeSH Dehydroepiandrosterone_Sulfate_analysis_MeSH M_Estradiol_MeSH S_analysis_MeSH Estradiol_analysis_MeSH M_Feasibility_Studies_MeSH M_Gonadal_Steroid_Hormones_MeSH S_analysis_MeSH Gonadal_Steroid_Hormones_analysis_MeSH P_Health_Status_MeSH M_Health_Surveys_MeSH M_Human_MeSH M_Hydrocortisone_MeSH S_analysis_MeSH Hydrocortisone_analysis_MeSH P_Life_Style_MeSH M_Male_MeSH P_Marital_Status_MeSH M_Middle_Aged_MeSH M_Pilot_Projects_MeSH M_Saliva_MeSH S_chemistry_MeSH Saliva_chemistry_MeSH P_Sexual_Behavior_MeSH M_Testosterone_MeSH S_analysis_MeSH Testosterone_analysis_MeSH 
****** 12639367
----K E
----T Failure of tibolone to potentiate the pharmacological effect of fluoxetine in postmenopausal major depression.
----A BACKGROUND: Perimenopausal depression has been attributed to physiological progressive estrogen decline. Estrogen and derivatives have some mood-enhancing effects, although studies of using estrogen as an antidepressant have had mixed results. The gonadomimetic drug tibolone stimulates estrogen receptors in a tissue-selective fashion, increasing the gonadal activity without causing some of the usual side effects of other estrogen preparations. METHODS: A total of 31 postmenopausal outpatients with a major depressive disorder (MDD) participated in the study. Sixteen received the antidepressant fluoxetine (20 mg/day) plus tibolone (2.5 mg/day), and 15 received the same dose of fluoxetine plus placebo, assigned in a randomized fashion. RESULTS: After 8 weeks of treatment, the two groups had a similar level of improvement in their depressive symptoms. Both treatments were well tolerated, without significant side effects. Pretreatment and posttreatment serum hormonal levels did not predict the final response. CONCLUSIONS: Combining tibolone and fluoxetine did not represent a more robust antidepressant response than fluoxetine alone in postmenopausal women with MDD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Comparative_Study_MeSH M_Depressive_Disorder_MeSH S_blood_MeSH Depressive_Disorder_blood_MeSH S_drug_therapy_MeSH Depressive_Disorder_drug_therapy_MeSH M_Double-Blind_Method_MeSH M_Estrogen_Receptor_Modulators_MeSH S_therapeutic_use_MeSH Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Estrogens_MeSH S_blood_MeSH Estrogens_blood_MeSH M_Female_MeSH M_Fluoxetine_MeSH S_therapeutic_use_MeSH Fluoxetine_therapeutic_use_MeSH M_Human_MeSH M_Mexico_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH P_Postmenopause_MeSH M_Serotonin_Uptake_Inhibitors_MeSH S_therapeutic_use_MeSH Serotonin_Uptake_Inhibitors_therapeutic_use_MeSH 
****** 12648884
----K E
----T A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women.
----A OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M P_Anxiety_MeSH M_China_MeSH P_Depression_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Menopause_MeSH S_psychology_MeSH Menopause_psychology_MeSH P_Postmenopause_MeSH M_Prospective_Studies_MeSH P_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12656701
----K E
----T Medical oophorectomy with and without estrogen add-back therapy in the prevention of migraine headache.
----A OBJECTIVES: To determine the preventive benefit of "medical oophorectomy" and transdermal estradiol in women with migraine. BACKGROUND: Epidemiological studies have demonstrated that declines in serum estrogen levels occurring during normal menstrual cycles can trigger headache in women with migraine. Prior to this study, no randomized controlled trials have evaluated whether minimizing these hormonal changes pharmacologically can prevent headache. METHODS: Twenty-one women with regular menstrual cycles and a diagnosis of migraine headache were enrolled. After a 2.5-month placebo run-in phase, all patients received a subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to induce a medical oophorectomy. One month later, while continuing goserelin, participants were randomized to receive a transdermal patch containing 100 microg of estradiol-17beta (gonadotropin-releasing hormone agonist/estradiol group, n = 9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n = 12) during a 2-month treatment phase. The primary outcome measure was the headache index, which was defined as the mean of pain severity ratings (0 to 10 scale) recorded three times per day by daily diary. Secondary outcome measures included headache disability, headache severity, headache frequency, and the percentage of headaches with a pain severity rating of 7 or greater. RESULTS: The headache index was significantly lower during the treatment period in the gonadotropin-releasing hormone agonist/estradiol group than in the gonadotropin-releasing hormone agonist/placebo group (P =.025). Similar improvements were observed in the gonadotropin-releasing hormone agonist/estradiol group for all secondary outcome measures with the exception of headache frequency, which was unchanged between the groups. Within the gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7% reduction (95% confidence interval, -64.4 to -3.0) in the headache index during the treatment phase when compared with the placebo run-in phase; no difference was seen between those phases within the gonadotropin-releasing hormone agonist/placebo group. CONCLUSIONS: Minimization of hormonal fluctuations with gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent headache in women who are premenopausal with migraine. The addition of transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy provides a modest preventive benefit.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Comparative_Study_MeSH M_Drug_Therapy__Combination_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Goserelin_MeSH S_pharmacology_MeSH Goserelin_pharmacology_MeSH S_therapeutic_use_MeSH Goserelin_therapeutic_use_MeSH M_Human_MeSH M_Menstruation_MeSH S_drug_effects_MeSH Menstruation_drug_effects_MeSH M_Migraine_MeSH S_etiology_MeSH Migraine_etiology_MeSH S_prevention_&_control_MeSH Migraine_prevention_&_control_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12659404
----K E
----T Evaluation of a unique oral contraceptive (Yasmin) in the management of premenstrual dysphoric disorder.
----A Over three-quarters of women experience some physical and emotional changes associated with the menstrual cycle. Irritability, tension, fatigue, depression, breast tenderness and bloating are among the most common premenstrual symptoms. Approximately 5-10% of women of childbearing age experience premenstrual symptoms to a degree that disrupts their functioning in the home or workplace and that meet criteria for premenstrual dysphoric disorder (PMDD). Serotonergic antidepressants are clearly effective for PMDD, with about 60% of subjects responding to this treatment in controlled studies. Oral contraceptives are commonly used to treat premenstrual symptoms but are an understudied intervention with no information on their efficacy for PMDD). The recent introduction of an oral contraceptive (Yasmin, Schering AG, Berlin, Germany), containing low-dose ethinylestradiol (EE) combined with a new progestogen, drospirenone (DRSP), may offer clinical efficacy for PMDD as a result of the unique pharmacological profile of this progestogen, which is a spirolactone derivative with antimineralocorticoid and antiandrogenic activity. A randomized, placebo-controlled study of DRSP/EE in women with PMDD found a consistently greater reduction of symptoms-from baseline for all 22 premenstrual symptoms assessed (using the Calendar of Premenstrual Experiences, COPE) and for the four statistically derived symptom factors in the group taking DRSP/EE compared to the placebo group. For appetite, acne and food craving (factor 3), the difference between the DRSP/EE group and the placebo group was statistically significant (p = 0.027). These preliminary results suggest the beneficial effect of DRSP/EE on PMDD and offer an alternative class of medication that also provides the range of benefits of oral contraception for women with PMDD.
----P Clinical_Trial Evaluation_Studies Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Androstenes_MeSH S_therapeutic_use_MeSH Androstenes_therapeutic_use_MeSH M_Comparative_Study_MeSH M_Contraceptives__Oral__Combined_MeSH S_therapeutic_use_MeSH Contraceptives__Oral__Combined_therapeutic_use_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Multivariate_Analysis_MeSH M_Patient_Satisfaction_MeSH M_Premenstrual_Syndrome_MeSH S_drug_therapy_MeSH Premenstrual_Syndrome_drug_therapy_MeSH S_psychology_MeSH Premenstrual_Syndrome_psychology_MeSH M_Probability_MeSH M_Reference_Values_MeSH M_Severity_of_Illness_Index_MeSH M_Treatment_Outcome_MeSH 
****** 12665046
----K E
----T Moclobemide in the treatment of hot flashes in postmenopausal women.
----A This randomized, prospective, double-blind study evaluated the efficacy and tolerability of moclobemide, a reversible, selective inhibitor of monoamine oxidase-A, in reducing the frequency and severity of hot flashes. Thirty postmenopausal women were enrolled, and 28 were allocated to 5 weeks of treatment with moclobemide 150 mg (group 1, n = 10), moclobemide 300 mg (group 2, n = 11), or placebo (group 3, n = 9). Data on hot flashes were recorded in a daily diary. Mean reductions in the hot flash severity score were 24.4% in the placebo group, 69.8% in group 1, and 35.0% in group 2. This large difference suggests that the beneficial effects were not due to a placebo effect. Moclobemide may be a new nonhormonal option for reducing the incidence, severity, and duration of hot flashes in postmenopausal women who do not wish to take estrogen or have contraindications to its use.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Analysis_of_Variance_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Moclobemide_MeSH S_pharmacology_MeSH Moclobemide_pharmacology_MeSH S_therapeutic_use_MeSH Moclobemide_therapeutic_use_MeSH M_Monoamine_Oxidase_Inhibitors_MeSH S_pharmacology_MeSH Monoamine_Oxidase_Inhibitors_pharmacology_MeSH S_therapeutic_use_MeSH Monoamine_Oxidase_Inhibitors_therapeutic_use_MeSH M_Postmenopause_MeSH M_Prospective_Studies_MeSH 
****** 12665638
----K E
----T Physician treatment of osteoporosis in response to heel ultrasound bone mineral density reports.
----A Optimal information that should be included in ultrasound (US) heel bone mineral density (BMD) reports is not known. If additional information about further evaluation of patients with low heel BMD were included in reports, would responses for treatment improve? We screened people at health fairs using the Sahara heel US machine. For those with a T-score of </= 1.0, letters were sent to their primary care physician notifying them of the result. Physicians were randomly assigned to (1) a standard letter, which recommended central bone density screening (dual X-ray absorptiometry [DXA]) and treatment if the BMD was low; or (2) an extended letter, which also outlined treatment strategies based on recommended subsequent central DXA scan results for a T-score of < 1.50 and also if < 2.00. The extended letter only increased the frequency of DXA testing from 30.1 to 37.2% (not a significant increase). Of 88 people with heel BMD </= 1.00 and not previously on any treatment, 25 of 45 (56%) were treated (calcium, estrogens, bisphosphonates, or calcitonin or a combination) after physicians received a standard letter and 30 of 43 (70%) after an extended letter (one-sided p = 0.084). Of people with T </= 1.9, and initially taking nothing more than calcium, 5 of 36 (13.9%) received additional treatment after physicians received a standard letter vs 9 of 41 (22.0%) after an extended letter (one-sided p = 0.180). For those with T </= 1.0 because of the screen 25 of 197 (12.7%) received additional treatment. One hundred forty-six of 194 (75%) individuals and received treatment with calcium or other medications, and 74 of 173 (43%) of individuals before screening and 141 of 195 (72%) after physicians received letters took calcium. Physicians regarded calcium alone as adequate treatment in many cases. There was no marked increase in treatment when additional information was provided to physicians regarding evaluation and treatment for low US heel BMD results.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Bone_Density_MeSH M_Calcaneus_MeSH S_physiology_MeSH Calcaneus_physiology_MeSH S_ultrasonography_MeSH Calcaneus_ultrasonography_MeSH M_Calcitonin_MeSH S_therapeutic_use_MeSH Calcitonin_therapeutic_use_MeSH M_Calcium_MeSH S_therapeutic_use_MeSH Calcium_therapeutic_use_MeSH M_Diphosphonates_MeSH S_therapeutic_use_MeSH Diphosphonates_therapeutic_use_MeSH M_Human_MeSH M_Mass_Screening_MeSH M_Osteoporosis_MeSH S_prevention_&_control_MeSH Osteoporosis_prevention_&_control_MeSH S_therapy_MeSH Osteoporosis_therapy_MeSH S_ultrasonography_MeSH Osteoporosis_ultrasonography_MeSH P_Physician's_Practice_Patterns_MeSH 
****** 12665701
----K E
----T Bone density changes with once weekly risedronate in postmenopausal women.
----A Risedronate 5 mg daily is approved by the Food and Drug Administration to treat postmenopausal osteoporosis. Gastrointestinal (GI) symptoms are common with daily bisphosphonates, but recent studies show that once weekly treatment may be better tolerated. Risedronate 30 mg is approved to treat Paget s disease of bone. In this retrospective study, we assessed the GI tolerability of 30 mg of risedronate once weekly and evaluated the effect on bone mineral density (BMD) in a subset of women. Review of patients treated in our osteoporosis clinic identified 150 postmenopausal women with low BMD treated with 30 mg of risedronate once weekly, between February 1998 and March 2001. Baseline GI symptoms or previous intolerance of bisphosphonates was present in 32 patients. An additional antiresorptive treatment was continued with risedronate in 50% of these patients (estrogen, raloxifene, or calcitonin). Risedronate 30 mg was taken once weekly with vitamin D 400 iu daily and 1200 mg of calcium daily. Patient age ranged from 46 to 86 yr. Baseline and followup BMD data were available in 36 patients. Of the 32 patients with baseline GI symptoms or previous intolerance of a bisphosphonate, 1 developed GI symptoms. In those patients with baseline and follow-up BMD results (n = 36), BMD increased 1.9% (p = 0.02) at the trochanter and 2.1% (p = 0.001) at the total hip. In conclusion 30 mg of risedronate once weekly increased BMD at the trochanter and total hip (p < 0.05). This dosage was well tolerated with a low incidence of GI side effects.
----P Journal_Article 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH M_Digestive_System_MeSH S_drug_effects_MeSH Digestive_System_drug_effects_MeSH M_Diphosphonates_MeSH S_adverse_effects_MeSH Diphosphonates_adverse_effects_MeSH M_Drug_Tolerance_MeSH M_Etidronic_Acid_MeSH S_administration_&_dosage_MeSH Etidronic_Acid_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Etidronic_Acid_analogs_&_derivatives_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Postmenopause_MeSH M_Retrospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vitamin_D_MeSH S_administration_&_dosage_MeSH Vitamin_D_administration_&_dosage_MeSH 
****** 12674130
----K E
----T Postmenopausal hormone therapy: cardiovascular risks.
----A (1) The WHI study was published in 2002: a randomised double-blind placebo-controlled clinical trial in more than 16 000 women with an average age of 63 years at enrollment. The paper reports data on the long-term adverse effects of combined equine estrogen-progestin hormone replacement therapy, taken for 5 years. (2) On average, a yearly excess of 19 severe adverse events per 10 000 women occurred in the estrogen-progestin group. Relative to the placebo group, there were an extra 8 pulmonary embolisms, 7 coronary events, 8 strokes and 8 cases of invasive breast cancer. In contrast, there were 6 fewer colorectal cancers and 5 fewer hip fractures in the active treatment group. (3) The differences in the frequency of coronary events and venous thromboembolism emerged after the first year of treatment, while the curves for stroke and breast cancer diverged after the second and fifth years, respectively. (4) The overall mortality rate did not differ between the two groups. (5) A placebo-controlled trial of the same hormone combination (HERS trial), given for 4.1 years as secondary prophylaxis against coronary heart disease was published in 1998. The drug was ineffective during the trial, and during unblinded post-trial follow-up of 2 321 women for an average of 2.7 years (HERS II study). (6) The estrogen-progestin combination used in these trials did not reduce the risk of coronary heart disease (in primary or secondary prophylaxis) or the risk of stroke. On the contrary, both risks increased. (7) The increased incidence of deep venous thrombosis and/or pulmonary embolism associated with estrogen-progestin replacement therapy was confirmed in these trials, even among women with no relevant history. (8) The WHI trial also confirmed the increased risk of breast cancer in women on hormone replacement therapy, but did not study its impact on outcome or mortality. (9) The WHI trial confirmed the beneficial impact of estrogen-progestin combination therapy on the risk of osteoporotic fracture. An average of 5 hip fractures were avoided each year per 10 000 women treated (10 versus 15 observed cases per 10 000 women per year), together with 6 symptomatic vertebral fractures (9 versus 15 cases) and 44 osteoporotic fractures (147 versus 191 cases). It is not known whether the benefit observed at the end of the trial persisted after the end of treatment. (10) In practice, the decision to prescribe hormone replacement therapy, and the optimal duration of treatment, must be weighed up according to each individual's risk factors. And the decision to treat or not to treat must be regularly re-assessed. Women must be informed of the potential risks and benefits, and must be monitored. They should also be advised not to use less well assessed treatments such as phytoestrogens, DHEA and tibolone. (11) Health authorities, especially in Europe, must organise comparative trials to assess the benefits and risks of other hormone combinations used by perimenopausal and postmenopausal women.
----P Journal_Article 
----M M_Breast_Neoplasms_MeSH S_chemically_induced_MeSH Breast_Neoplasms_chemically_induced_MeSH M_Cardiovascular_Diseases_MeSH S_chemically_induced_MeSH Cardiovascular_Diseases_chemically_induced_MeSH M_Comparative_Study_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Human_MeSH M_Progestins_MeSH S_adverse_effects_MeSH Progestins_adverse_effects_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH M_Women's_Health_Services_MeSH 
****** 12672913
----K E
----T Controlled high meat diets do not affect calcium retention or indices of bone status in healthy postmenopausal women.
----A Calcium balance is decreased by an increased intake of purified proteins, although the effects of common dietary sources of protein (like meat) on calcium economy remain controversial. We compared the effects of several weeks of controlled high and low meat diets on body calcium retention, using sensitive radiotracer and whole body scintillation counting methodology. Healthy postmenopausal women (n = 15) consumed diets with similar calcium content (approximately 600 mg), but either low or high in meat (12 vs. 20% of energy as protein) for 8 wk each, in a randomized crossover design. After 4 wk of equilibration of each diet, calcium retention was measured by extrinsically labeling the 2-d menu with (47)Ca, followed by whole body scintillation counting for 28 d. Urinary and blood indicators of bone metabolism were also determined for each diet. Calcium retention was not different during the high and low meat dietary periods (d 28, mean +/- pooled SD: 17.1 and 15.6%, +/-0.6%, respectively; P = 0.09). An initially higher renal acid excretion in subjects consuming the high meat compared with the low meat diet decreased significantly with time. The diets did not affect urinary calcium loss or indicators of bone metabolism. In conclusion, under controlled conditions, a high meat compared with a low meat diet for 8 wk did not affect calcium retention or biomarkers of bone metabolism in healthy postmenopausal women. Calcium retention is not reduced when subjects consume a high protein diet from common dietary sources such as meat.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Biological_Markers_MeSH P_Bone_Density_MeSH M_Calcium_MeSH S_metabolism_MeSH Calcium_metabolism_MeSH M_Cross-Over_Studies_MeSH P_Diet_MeSH M_Female_MeSH M_Human_MeSH M_Hydrogen-Ion_Concentration_MeSH M_Intestinal_Absorption_MeSH P_Meat_MeSH M_Middle_Aged_MeSH M_Reference_Values_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Urinalysis_MeSH 
****** 12678210
----K E
----T Isoflavones and the prevention and treatment of prostate disease: is there a role?
----A Epidemiologic and experimental data suggest that isoflavones have benefits for preventing and treating some prostate disease. Isoflavone supplements may therefore be an important tool for men concerned about prostate disease, such as those with benign prostatic hypertrophy undergoing watchful waiting or those concerned about the potential for prostate cancer. Conclusive proof of a relationship between isoflavones and the prevention and treatment of prostate disease can only come from prospective, randomized, controlled clinical trials.
----P Case_Reports Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH P_Dietary_Supplements_MeSH M_Follow-Up_Studies_MeSH M_Human_MeSH M_Incidence_MeSH M_Isoflavones_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Prostatic_Diseases_MeSH S_drug_therapy_MeSH Prostatic_Diseases_drug_therapy_MeSH S_prevention_&_control_MeSH Prostatic_Diseases_prevention_&_control_MeSH M_Prostatic_Hyperplasia_MeSH S_drug_therapy_MeSH Prostatic_Hyperplasia_drug_therapy_MeSH S_prevention_&_control_MeSH Prostatic_Hyperplasia_prevention_&_control_MeSH M_Prostatic_Neoplasms_MeSH S_epidemiology_MeSH Prostatic_Neoplasms_epidemiology_MeSH S_prevention_&_control_MeSH Prostatic_Neoplasms_prevention_&_control_MeSH M_Risk_Assessment_MeSH M_Sensitivity_and_Specificity_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12695269
----K E
----T Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial.
----A BACKGROUND: Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT. METHODS: The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability. RESULTS: Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo. CONCLUSIONS: A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Alendronate_MeSH S_pharmacology_MeSH Alendronate_pharmacology_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Bone_Resorption_MeSH S_prevention_&_control_MeSH Bone_Resorption_prevention_&_control_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Ilium_MeSH S_drug_effects_MeSH Ilium_drug_effects_MeSH M_International_Cooperation_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Single-Blind_Method_MeSH M_Spine_MeSH S_drug_effects_MeSH Spine_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12698204
----K E
----T Strontium ranelate: a new paradigm in the treatment of osteoporosis.
----A Not one of the currently available medications has, so far, unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once osteoporosis is established. Therefore, several new therapies are currently under development to optimize the risk/benefit ratio of osteoporosis treatment. Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable nonradioactive strontium. In vitro, strontium ranelate increases collagen and noncollagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cell replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cell and collagen, as well as noncollagenic protein synthesis in osteoblasts, provides substantial evidence to categorize strontium ranelate as a bone-forming agent. In the isolated rat osteoclast assay, a pre-incubation of bone slices with strontium ranelate induced a dose- dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both carbonic anhydrase II and the alpha-subunit of the vitronectin receptor. These effects showing that strontium ranelate significantly affects bone resorption due to a direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation, are compatible with the profile of an anti-resorptive drug. In normal rats, administration of strontium ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. Strontium ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg and 1 g of strontium ranelate were compared with a placebo. At the conclusion of the study, the percent variation of lumbar-adjusted bone mineral density from baseline was significantly different in the group receiving 1 g/day of strontium ranelate compared with placebo (+1.41% vs. -0.98%, respectively). Increase in total hip and neck bone mineral density averages, respectively, 3.2% and 2.5%. Strontium ranelate does not induce any significant adverse reaction compared with those observed in women receiving a placebo for the same duration. In a phase II study, the effect of strontium ranelate in postmenopausal women with vertebral osteoporotic fractures was assessed during a double-blind, placebo-controlled trial. Doses of 500 mg, 1 g and 2 g daily of strontium ranelate or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar-adjusted bone mineral density of the group receiving 2 g of strontium ranelate was + 2.97%. This result was significantly different compared with placebo. A significant increase in bone alkaline phosphatase and, over a 6-month period, a significant decrease in urinary-pyridium crosslinks (NTX) were evidenced. During the second year of treatment, the dose of 2 g was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralization defects. The same percentage of withdrawals following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. The compound was further investigated in a large phase III program that included two extensive trials for the treatment of severe osteoporosis, one assessing the effects of strontium ranelate on the risk of vertebral fractures (SOTI) and one evaluating its effects on peripheral (nonspinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates, revealed a 41% reduction in the relative risk of expein the relative risk of experiencing a first new vertebral fracture with strontium ranelate, throughout the 3-year study, compared with placebo. The TROPOS study, showed a significant (p = 0.05) reduction in the relative risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study compared with placebo in the intention-to-treat population. A 41% reduction in the relative risk of experiencing a hip fracture was demonstrated in the per protocol population. All these results imply that strontium ranelate is a new, effective and safe treatment for vertebral and nonvertebral osteoporosis, with a unique mode of action.
----P Journal_Article Review Review__Tutorial 
----M M_Animals_MeSH M_Biological_Availability_MeSH M_Bone_and_Bones_MeSH S_drug_effects_MeSH Bone_and_Bones_drug_effects_MeSH M_Disease_Models__Animal_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH P_Organometallic_Compounds_MeSH S_pharmacokinetics_MeSH Organometallic_Compounds_pharmacokinetics_MeSH S_pharmacology_MeSH Organometallic_Compounds_pharmacology_MeSH S_therapeutic_use_MeSH Organometallic_Compounds_therapeutic_use_MeSH P_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_metabolism_MeSH Osteoporosis__Postmenopausal_metabolism_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Randomized_Controlled_Trials_MeSH P_Thiophenes_MeSH S_pharmacokinetics_MeSH Thiophenes_pharmacokinetics_MeSH S_pharmacology_MeSH Thiophenes_pharmacology_MeSH S_therapeutic_use_MeSH Thiophenes_therapeutic_use_MeSH M_Tissue_Distribution_MeSH 
****** 12706932
----K E
----T Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women.
----A OBJECTIVES: We investigated whether the route of estrogen replacement therapy (ET) is the major determinant of C-reactive protein (CRP) in postmenopausal women. BACKGROUND: Recent studies demonstrated that oral ET causes a sustained increase in CRP, implicating a proinflammatory effect. Because CRP is synthesized in the liver, we hypothesized that estrogen-induced CRP elevation is related to first-pass hepatic metabolism. METHODS: In 21 postmenopausal women, we conducted a randomized, crossover, placebo-controlled study to compare the effects of transdermal versus oral ET on CRP and inflammatory cytokines. We measured CRP, interleukin (IL)-1-beta, IL-6, and tumor necrosis factor-alpha before and after eight weeks of transdermal estradiol (E(2)) (100 microg/day), oral conjugated estrogen (CEE) (0.625 mg/day), or placebo. Insulin-like growth factor-1 (IGF-1), a hepatic-derived anabolic peptide, was also measured. RESULTS: Transdermal E(2) had no effect on CRP or IGF-1 levels. In contrast, eight weeks of oral conjugated estrogens caused a more than twofold increase in CRP and a significant reduction in IGF-1 (p < 0.01) in the same women. The magnitude of increase in CRP was inversely correlated to the decrease in IGF-1 (r = -0.49, p = 0.008). Neither transdermal E(2) nor oral CEE had any effects on the plasma concentrations of cytokines that promote CRP synthesis. CONCLUSIONS: In postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect. An increase in CRP levels is accompanied by a reduction in IGF-1, an anti-inflammatory growth factor. Because CRP is a powerful predictor of an adverse prognosis in otherwise healthy postmenopausal women, the route of administration may be an important consideration in minimizing the adverse effects of ET on cardiovascular outcomes.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Administration__Oral_MeSH M_Analysis_of_Variance_MeSH M_C-Reactive_Protein_MeSH S_metabolism_MeSH C-Reactive_Protein_metabolism_MeSH M_Cross-Over_Studies_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_metabolism_MeSH Insulin-Like_Growth_Factor_I_metabolism_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Liver_MeSH S_metabolism_MeSH Liver_metabolism_MeSH M_Menopause_MeSH S_blood_MeSH Menopause_blood_MeSH S_metabolism_MeSH Menopause_metabolism_MeSH M_Middle_Aged_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12720542
----K E
----T Progesterone effects during sequential hormone replacement therapy.
----A OBJECTIVE: The aim was to investigate the effect on mood and the physical symptoms of two dosages of natural progesterone and a placebo in postmenopausal women with and without a history of premenstrual syndrome (PMS). DESIGN: A randomized, placebo-controlled, double-blind, crossover study was performed. METHOD: Postmenopausal women (n=36) with climacteric symptoms were recruited. They received 2 mg estradiol continuously during three 28-day cycles. Vaginal progesterone suppositories with 800 mg/day, 400 mg/day, or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. RESULTS: Women without a history of PMS showed cyclicity in both negative mood and physical symptoms while on 400 mg/day progesterone but not on the higher dose or the placebo. Women without a history of PMS had more physical symptoms on progesterone treatment compared with placebo. Women with prior PMS reported no progesterone-induced symptom cyclicity. CONCLUSION: In women without prior PMS natural progesterone caused negative mood effects similar to those induced by synthetic progestogens.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Medical_Records_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Periodicity_MeSH M_Premenstrual_Syndrome_MeSH M_Progesterone_MeSH S_administration_&_dosage_MeSH Progesterone_administration_&_dosage_MeSH S_blood_MeSH Progesterone_blood_MeSH S_therapeutic_use_MeSH Progesterone_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Suppositories_MeSH 
****** 12727949
----K E
----T Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy.
----A Previous studies have indicated that the addition of progestins during sequential hormonal replacement therapy (HRT) causes negative mood and physical symptoms. History of premenstrual syndrome, type of progestin, and dose of progestin have thus far been shown to influence the progestin-induced adverse mood symptoms during HRT. The aim of this study was to compare adverse mood effects of two different doses of estradiol, in combination with a progestin, during postmenopausal HRT. Twenty-eight perimenopausal women were included in this randomized, double-blind, crossover study comparing 2- or 3-mg continuous estradiol, with an addition of 10 mg medroxyprogesterone acetate on d 17-28 during each treatment cycle. The main outcome measures were mood and physical symptoms kept on a daily rating scale. Together with the progestin, the higher dose of estrogen caused significantly more negative mood symptoms than the lower dose. Tension, irritability, and depressed mood were all significantly augmented during the progestin phase of cycles with 3 mg estradiol (P < 0.001). Physical symptoms also increased during the progestin phase of 3-mg estradiol cycles (P < 0.001), whereas positive mood symptoms were less affected. The only positive mood that changed with estrogen dose was friendliness, which decreased during the progestin phase of high estradiol cycles compared with cycles with lower estradiol (P < 0.05). Our conclusion is that an increase of the estrogen dose accentuates negative mood and physical symptoms during the progestin phase of sequential hormonal therapy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Cross-Over_Studies_MeSH M_Depression_MeSH S_chemically_induced_MeSH Depression_chemically_induced_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Interactions_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Irritable_Mood_MeSH S_drug_effects_MeSH Irritable_Mood_drug_effects_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Middle_Aged_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12728189
----K E
----T Counseling the adolescent about contraception.
----A 
----P Journal_Article Review Review__Tutorial 
----M M_Adolescent_MeSH P_Adolescent_Behavior_MeSH P_Contraception_MeSH S_methods_MeSH Contraception_methods_MeSH P_Counseling_MeSH M_Female_MeSH M_Human_MeSH P_Pediatrics_MeSH M_Pregnancy_MeSH M_Pregnancy_in_Adolescence_MeSH S_prevention_&_control_MeSH Pregnancy_in_Adolescence_prevention_&_control_MeSH P_Sexual_Behavior_MeSH 
****** 12734027
----K E
----T Long-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis.
----A Recent studies have called into question whether the risks of hormone replacement therapy (HRT) outweigh its long-term benefits. There is a clear causal relationship between estrogen deficiency and osteoporosis. Postmenopausal status or estrogen-deficiency at any age significantly increases a patient's risk for osteoporosis and subsequent fragility fractures. Estrogen, in various formulations, is currently FDA-indicated for the prevention of osteoporosis. However, estrogen is not FDA-approved for the treatment of osteoporosis. Recent randomized clinical trials have demonstrated that estrogen significantly reduces fractures among osteoporotic postmenopausal women. Most postmenopausal women choose to use estrogen for relief of vasomotor symptoms and urogenital atrophy. HRT should be limited to osteoporosis prevention in women with significant ongoing vasomotor symptoms who are not at an increased risk for cardiovascular disease. An annual, individualized, risk/benefit reassessment should be performed on these patients. Further research is needed to assess the potential risks and benefits of various formulations, combinations, doses, and delivery routes of estrogen for postmenopausal women.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Cardiovascular_Diseases_MeSH S_physiopathology_MeSH Cardiovascular_Diseases_physiopathology_MeSH M_Dose-Response_Relationship__Drug_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens_adverse_effects_MeSH S_deficiency_MeSH Estrogens_deficiency_MeSH M_Female_MeSH M_Fractures_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_complications_MeSH Osteoporosis__Postmenopausal_complications_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH M_United_States_MeSH M_Vasomotor_System_MeSH S_drug_effects_MeSH Vasomotor_System_drug_effects_MeSH P_Women's_Health_MeSH 
****** 12642636
----K E
----T Postmenopausal hormones--therapy for symptoms only.
----A 
----P Comment Journal_Article 
----M M_Breast_Neoplasms_MeSH S_chemically_induced_MeSH Breast_Neoplasms_chemically_induced_MeSH M_Cardiovascular_Diseases_MeSH S_chemically_induced_MeSH Cardiovascular_Diseases_chemically_induced_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Colonic_Neoplasms_MeSH S_prevention_&_control_MeSH Colonic_Neoplasms_prevention_&_control_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Female_MeSH M_Hip_Fractures_MeSH S_prevention_&_control_MeSH Hip_Fractures_prevention_&_control_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Quality_of_Life_MeSH M_Risk_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12642637
----K I
----T Effects of estrogen plus progestin on health-related quality of life.
----A BACKGROUND: The Women's Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life. METHODS: The WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women. RESULTS: Randomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes. CONCLUSIONS: In this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Depression_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Health_Status_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Linear_Models_MeSH M_Mental_Health_MeSH M_Middle_Aged_MeSH M_Progestins_MeSH S_pharmacology_MeSH Progestins_pharmacology_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH P_Quality_of_Life_MeSH M_Sexual_Behavior_MeSH S_drug_effects_MeSH Sexual_Behavior_drug_effects_MeSH M_Sleep_Disorders_MeSH S_drug_therapy_MeSH Sleep_Disorders_drug_therapy_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12741429
----K E
----T Estradiol in premenstrual asthma: a double-blind, randomized, placebo-controlled, crossover study.
----A STUDY OBJECTIVES: To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: Respiratory clinic and clinical research center. SUBJECTS: Twelve women with documented premenstrual asthma (> or = 20% premenstrual worsening of asthma symptoms and/or of peak expiratory flow [PEF] during a 1-month screening phase). INTERVENTION: Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 (i.e., premenstrually, or before the onset of menses) in the first cycle and then crossed over to the other arm in the second cycle. Throughout both cycles, the women recorded daily morning and evening PEF readings and asthma symptoms. MEASUREMENTS AND MAIN RESULTS: Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 (follicular phase), 22 (luteal phase), and 28 (premenstrually) of both the estradiol and placebo cycles. During the two premenstrual visits, the Asthma Quality of Life Questionnaire was administered. No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores. The area under the curve (AUC) for the composite asthma symptoms versus time profile was numerically, but not statistically, lower (denoting less severe symptoms) during the estradiol cycle than during the placebo cycle. Likewise, no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle. Despite differences (p<0.05) in day-28 estradiol concentrations for estradiol and placebo cycles, no significant differences were found in forced expiratory volume in 1 second, serum endothelin-1, serum and urine eosinophil protein X, urine leukotriene E4, or quality-of-life scores. CONCLUSION: Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control. As in the case of premenstrual syndrome, the placebo effect may be prominent in premenstrual asthma. Further trials, involving women with more severe asthma under poorer control, are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Anti-Inflammatory_Agents_MeSH S_administration_&_dosage_MeSH Anti-Inflammatory_Agents_administration_&_dosage_MeSH S_blood_MeSH Anti-Inflammatory_Agents_blood_MeSH S_therapeutic_use_MeSH Anti-Inflammatory_Agents_therapeutic_use_MeSH M_Antioxidants_MeSH S_administration_&_dosage_MeSH Antioxidants_administration_&_dosage_MeSH S_analysis_MeSH Antioxidants_analysis_MeSH S_therapeutic_use_MeSH Antioxidants_therapeutic_use_MeSH M_Asthma_MeSH S_drug_therapy_MeSH Asthma_drug_therapy_MeSH M_Biological_Markers_MeSH S_analysis_MeSH Biological_Markers_analysis_MeSH M_Creatinine_MeSH S_urine_MeSH Creatinine_urine_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Endothelin-1_MeSH S_blood_MeSH Endothelin-1_blood_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Leukotriene_E4_MeSH S_urine_MeSH Leukotriene_E4_urine_MeSH P_Menstrual_Cycle_MeSH M_Progesterone_MeSH S_blood_MeSH Progesterone_blood_MeSH M_Quality_of_Life_MeSH M_Ribonucleases_MeSH S_blood_MeSH Ribonucleases_blood_MeSH S_urine_MeSH Ribonucleases_urine_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12742557
----K E
----T Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study.
----A In this prospective, controlled, randomized study, we compared the effect of a low-dose 21-day combined oral contraceptive (COC) containing 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GTD) (Group A; n = 19) with an ultra-low-dose 24-day COC containing 15 microg EE and 60 microg GTD (Group B; n = 18) on bone turnover and bone mineral density (BMD) in young, fertile women. Nineteen healthy fertile women were used as untreated controls (Group C). At 3, 6, 9 and 12 months of the study serum osteocalcin (BGP), urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) were measured in all subjects. At baseline and after 12 months BMD was determined at lumbar spine by dual-energy X-ray absorptiometry in all patients. In both Groups A and B, urinary levels of PYD and D-PYD at 6, 9 and 12 months, were significantly reduced in comparison with basal values and with control subjects (p < 0.05). No significant differences in urinary PYD and D-PYD levels were observed between Groups A and B during the entire period of treatment. At 12 months, no statistically significant difference in spinal BMD values was detected between the three groups and in comparison with basal values. The present study suggests that the two COCs could exert a similar positive effect on bone turnover in young postadolescent women, without any significant and appreciable modification of BMD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Amino_Acids_MeSH S_urine_MeSH Amino_Acids_urine_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Resorption_MeSH S_metabolism_MeSH Bone_Resorption_metabolism_MeSH M_Comparative_Study_MeSH M_Contraceptives__Oral__Combined_MeSH S_pharmacology_MeSH Contraceptives__Oral__Combined_pharmacology_MeSH M_Densitometry__X-Ray_MeSH M_Drug_Administration_Schedule_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Human_MeSH M_Norpregnenes_MeSH S_administration_&_dosage_MeSH Norpregnenes_administration_&_dosage_MeSH M_Osteocalcin_MeSH S_blood_MeSH Osteocalcin_blood_MeSH M_Prospective_Studies_MeSH M_Treatment_Outcome_MeSH 
****** 12752630
----K E
----T A roundtable discussion of aromatase inhibitors as therapy for breast cancer.
----A This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second-line therapy in postmenopausal women with hormone-responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first-line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease.
----P Consensus_Development_Conference Journal_Article Review 
----M M_Androstadienes_MeSH S_therapeutic_use_MeSH Androstadienes_therapeutic_use_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Aromatase_MeSH S_antagonists_&_inhibitors_MeSH Aromatase_antagonists_&_inhibitors_MeSH M_Breast_Neoplasms_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH M_Clinical_Trials__Phase_III_MeSH M_Enzyme_Inhibitors_MeSH S_therapeutic_use_MeSH Enzyme_Inhibitors_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Nitriles_MeSH S_therapeutic_use_MeSH Nitriles_therapeutic_use_MeSH M_Postmenopause_MeSH M_Support__Non-U_S__Gov't_MeSH M_Triazoles_MeSH S_therapeutic_use_MeSH Triazoles_therapeutic_use_MeSH 
****** 12752890
----K E
----T Acute administration of conjugated equine oestrogen does not improve exercise-induced myocardial ischaemia in men with coronary artery disease.
----A BACKGROUND: The parenteral administration of oestradiol acutely protects against exercise-induced myocardial ischaemia in women, but whether this effect is sex-specific is not known. AIMS: The effects of acutely administered conjugated equine oestrogen on exercise-induced myocardial ischaemia in men with established coronary heart disease were investigated in a randomized, placebo-controlled, double-blind cross-over trial. METHODS: Twenty men, aged 62 +/- 11.6 years, with reproducible exercise-induced myocardial ischaemia were treated with either intravenous conjugated equine oestrogen (25 mg) or saline prior to undergoing an exercise stress test. Primary end-points were total exercise time and time to 1 mm ST-segment depression. RESULTS: All participants completed the protocol. Total exercise time exceeded the baseline value in 17 of the 20 men following saline, and in 17 of the 20 men following oestrogen pretreatment. Time to 1 mm ST-segment depression exceeded the baseline value in 14 of the 19 men following saline, and following oestrogen administration, exceeded baseline in 13 of the 19 men. There was no significant difference between the two treatments in either time to 1 mm ST-segment depression or total exercise time. A period effect was apparent for total exercise time (P = 0.05) but not for time to ST-segment depression. CONCLUSION: Acute parenteral oestrogen therapy did not increase total exercise time or time to the onset of electrocardiographic changes of ischaemia in men with chronic stable coronary artery disease. These findings contrast the favourable effects of oestrogen in women in comparable studies and indicate a sex specificity for the acute cardiovascular effects of oestrogen.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Coronary_Arteriosclerosis_MeSH S_drug_therapy_MeSH Coronary_Arteriosclerosis_drug_therapy_MeSH S_physiopathology_MeSH Coronary_Arteriosclerosis_physiopathology_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Exercise_MeSH M_Exercise_Test_MeSH M_Gonadal_Steroid_Hormones_MeSH S_therapeutic_use_MeSH Gonadal_Steroid_Hormones_therapeutic_use_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Myocardial_Ischemia_MeSH S_diagnosis_MeSH Myocardial_Ischemia_diagnosis_MeSH S_drug_therapy_MeSH Myocardial_Ischemia_drug_therapy_MeSH S_etiology_MeSH Myocardial_Ischemia_etiology_MeSH P_Sex_Factors_MeSH 
****** 12759324
----K E
----T Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial.
----A CONTEXT: Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis, but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown. OBJECTIVE: To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe, and how they compare with monotherapy in community-dwelling elderly women. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTING AND PARTICIPANTS: Five hundred seventy-three community-dwelling women age 65 years or older were screened: 485 completed screening and 373 (aged 65 to 90 years) were randomized following a 3-month, open-label, run-in phase with hormone replacement and alendronate placebo. The trial was conducted at a single academic US medical center from January 1996 to May 2001. INTERVENTIONS: Participants were randomly assigned in a 2 x 2 factorial design to receive hormone replacement (conjugated equine estrogen, 0.625 mg/d, with or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10 mg daily, both agents, or neither. All participants received calcium and vitamin D supplements. MAIN OUTCOME MEASURES: Annualized change in bone mineral density of the hip and spine and occurrence of adverse events. RESULTS: Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy, with mean (SD) increases of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean (SD) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; P<.05, respectively), and alendronate resulted in more responders to therapy. All therapies were well tolerated and participant retention was 90% at 3 years. CONCLUSIONS: Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort. Alendronate was superior to hormone replacement, and combination therapy was superior to either therapy alone. Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Alendronate_MeSH S_therapeutic_use_MeSH Alendronate_therapeutic_use_MeSH M_Bone_Density_MeSH M_Double-Blind_Method_MeSH M_Drug_Therapy__Combination_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12763515
----K E
----T The menopause and HRT. HRT and cognitive decline.
----A It is biologically plausible that hormone replacement therapy (HRT) would be protective against cognitive decline and Alzheimer's disease (AD). We review observational and randomized trials to determine whether HRT might protect against cognitive decline in cognitively unimpaired and demented women. We also address issues of clinical relevance, including duration and type of treatment and patient characteristics, including type of menopause (surgical versus natural), age, education and menopausal symptoms. Differences in participant characteristics and testing methods limit the ability to draw conclusions across randomized studies of HRT in non-demented women. The available evidence suggests no detrimental effect of HRT on cognitive function and inconsistent benefits on verbal memory and reasoning, frontal functions and speeded attention. Meta-analyses of observational trials suggest that HRT protects against the development of AD, but randomized trials indicate no long-lasting benefit in patients with AD. Evidence is insufficient to recommend HRT to maintain cognitive function.
----P Journal_Article Review Review__Tutorial 
----M M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Dementia_MeSH S_prevention_&_control_MeSH Dementia_prevention_&_control_MeSH M_Educational_Status_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Postmenopause_MeSH M_Progestins_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Randomized_Controlled_Trials_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12771112
----K E
----T Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
----A CONTEXT: Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy. OBJECTIVE: To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS. INTERVENTION: Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303). MAIN OUTCOME MEASURES: Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment. RESULTS: The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72). CONCLUSIONS: Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Cognition_Disorders_MeSH S_chemically_induced_MeSH Cognition_Disorders_chemically_induced_MeSH S_diagnosis_MeSH Cognition_Disorders_diagnosis_MeSH S_epidemiology_MeSH Cognition_Disorders_epidemiology_MeSH M_Dementia_MeSH S_chemically_induced_MeSH Dementia_chemically_induced_MeSH S_diagnosis_MeSH Dementia_diagnosis_MeSH S_epidemiology_MeSH Dementia_epidemiology_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Neuropsychological_Tests_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Proportional_Hazards_Models_MeSH M_Risk_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12771113
----K E
----T Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
----A CONTEXT: Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women. OBJECTIVE: To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002. INTERVENTIONS: Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236). MAIN OUTCOME MEASURE: Global cognitive function measured annually with the Modified Mini-Mental State Examination. RESULTS: The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P =.03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (> or =2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P =.008). CONCLUSIONS: Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Cognition_Disorders_MeSH S_chemically_induced_MeSH Cognition_Disorders_chemically_induced_MeSH S_diagnosis_MeSH Cognition_Disorders_diagnosis_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Neuropsychological_Tests_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_adverse_effects_MeSH Progesterone_Congeners_adverse_effects_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Risk_MeSH 
****** 12773935
----K E
----T The endocrinology of gonadal involution: menopause and andropause.
----A Most aging individuals die from atherosclerosis, cancer or dementia. In the oldest old also loss of muscle strength resulting in frailty becomes the limiting factor for an individual's chances of living an independent life until death. Two hormonal changes mark the aging process in man. In women an acute drop in estrogen production by the ovaries around the age of 50 initiates a symptom complex called menopause. In men a more subtle drop of testosterone bioactivity from 40 yrs onwards might be accompanied by more difficulty to recognize symptomatology (andropause). Hormone replacement strategies in elderly women and males with estrogens or androgens, respectively, has some clear advantages, but is currently controversial, because of the occurrence of adverse effects.
----P Journal_Article Review Review__Tutorial 
----M M_Adult_MeSH M_Aged_MeSH M_Aged__80_and_over_MeSH P_Aging_MeSH M_Bone_Density_MeSH M_Cardiovascular_Diseases_MeSH M_Dementia_MeSH M_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens_MeSH S_physiology_MeSH Estrogens_physiology_MeSH M_Exercise_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH M_Human_MeSH M_Male_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Muscle__Skeletal_MeSH S_anatomy_&_histology_MeSH Muscle__Skeletal_anatomy_&_histology_MeSH S_physiology_MeSH Muscle__Skeletal_physiology_MeSH M_Ovary_MeSH S_physiology_MeSH Ovary_physiology_MeSH M_Randomized_Controlled_Trials_MeSH M_Testis_MeSH S_physiology_MeSH Testis_physiology_MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Testosterone_adverse_effects_MeSH S_physiology_MeSH Testosterone_physiology_MeSH 
****** 12775404
----K E
----T Baseline experience with Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (WHIMS).
----A The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure of exam subscales.The distribution of 3MS scores at baseline was compressed in WHIMS compared to population-based data. Mean 3MS scores (overall 95.1) tended to decrease with age and increase with education, however these associations varied among ethnic groups (p< 0.0001) even after adjustment for health, physical disability and occupation attainment. Four factors accounted for 37% of the total variance. Each varied with education and ethnicity; the two most prominent factors also varied with age. Despite relatively narrow distributions in WHIMS, baseline 3MS scores retained associations with age and education. These associations varied among ethnic groups, so that care must be taken in comparing data across populations.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aged__80_and_over_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Dementia_MeSH S_epidemiology_MeSH Dementia_epidemiology_MeSH S_prevention_&_control_MeSH Dementia_prevention_&_control_MeSH M_Demography_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Factor_Analysis__Statistical_MeSH M_Female_MeSH M_Geriatric_Assessment_MeSH M_Human_MeSH M_Incidence_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH P_Mental_Status_Schedule_MeSH M_Psychometrics_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_United_States_MeSH S_epidemiology_MeSH United_States_epidemiology_MeSH 
****** 12783932
----K E
----T A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers.
----A BACKGROUND: Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. METHODS: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. RESULTS: Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P =.81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. CONCLUSIONS: The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Antineoplastic_Agents__Hormonal_MeSH S_administration_&_dosage_MeSH Antineoplastic_Agents__Hormonal_administration_&_dosage_MeSH S_therapeutic_use_MeSH Antineoplastic_Agents__Hormonal_therapeutic_use_MeSH M_Breast_Neoplasms_MeSH S_blood_MeSH Breast_Neoplasms_blood_MeSH S_chemistry_MeSH Breast_Neoplasms_chemistry_MeSH S_drug_therapy_MeSH Breast_Neoplasms_drug_therapy_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Drug_Administration_Schedule_MeSH M_Estrogen_Receptor_Modulators_MeSH S_administration_&_dosage_MeSH Estrogen_Receptor_Modulators_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Estrogens_MeSH S_blood_MeSH Estrogens_blood_MeSH M_Female_MeSH M_Gene_Expression_Regulation__Neoplastic_MeSH S_drug_effects_MeSH Gene_Expression_Regulation__Neoplastic_drug_effects_MeSH M_Human_MeSH M_Immunohistochemistry_MeSH M_Ki-67_Antigen_MeSH S_blood_MeSH Ki-67_Antigen_blood_MeSH M_Middle_Aged_MeSH M_Research_Design_MeSH M_Support__Non-U_S__Gov't_MeSH M_Tamoxifen_MeSH S_administration_&_dosage_MeSH Tamoxifen_administration_&_dosage_MeSH S_therapeutic_use_MeSH Tamoxifen_therapeutic_use_MeSH M_Tumor_Markers__Biological_MeSH S_blood_MeSH Tumor_Markers__Biological_blood_MeSH 
****** 12783912
----K E
----T Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.
----A CONTEXT: Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE: To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING: Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS: Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS: Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). RESULTS: The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Activities_of_Daily_Living_MeSH M_Aged_MeSH M_Alzheimer_Disease_MeSH S_drug_therapy_MeSH Alzheimer_Disease_drug_therapy_MeSH S_physiopathology_MeSH Alzheimer_Disease_physiopathology_MeSH M_Anti-Inflammatory_Agents__Non-Steroidal_MeSH S_adverse_effects_MeSH Anti-Inflammatory_Agents__Non-Steroidal_adverse_effects_MeSH S_therapeutic_use_MeSH Anti-Inflammatory_Agents__Non-Steroidal_therapeutic_use_MeSH M_Cyclooxygenase_Inhibitors_MeSH S_adverse_effects_MeSH Cyclooxygenase_Inhibitors_adverse_effects_MeSH S_therapeutic_use_MeSH Cyclooxygenase_Inhibitors_therapeutic_use_MeSH M_Disease_Progression_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Human_MeSH M_Isoenzymes_MeSH S_antagonists_&_inhibitors_MeSH Isoenzymes_antagonists_&_inhibitors_MeSH M_Lactones_MeSH S_adverse_effects_MeSH Lactones_adverse_effects_MeSH S_therapeutic_use_MeSH Lactones_therapeutic_use_MeSH M_Male_MeSH M_Naproxen_MeSH S_adverse_effects_MeSH Naproxen_adverse_effects_MeSH S_therapeutic_use_MeSH Naproxen_therapeutic_use_MeSH M_Neuropsychological_Tests_MeSH M_Proportional_Hazards_Models_MeSH M_Prostaglandin-Endoperoxide_Synthase_MeSH M_Regression_Analysis_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Treatment_Outcome_MeSH 
****** 12783913
----K E
----T Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial.
----A CONTEXT: Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. OBJECTIVE: To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. PATIENTS: A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. INTERVENTION: After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. MAIN OUTCOME MEASURES: Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity). RESULTS: Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. CONCLUSION: Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Delayed-Action_Preparations_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH M_Health_Status_Indicators_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Logistic_Models_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Paroxetine_MeSH S_administration_&_dosage_MeSH Paroxetine_administration_&_dosage_MeSH S_therapeutic_use_MeSH Paroxetine_therapeutic_use_MeSH M_Serotonin_Uptake_Inhibitors_MeSH S_administration_&_dosage_MeSH Serotonin_Uptake_Inhibitors_administration_&_dosage_MeSH S_therapeutic_use_MeSH Serotonin_Uptake_Inhibitors_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12792289
----K E
----T Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study.
----A OBJECTIVE: This study examines the effects of a dietary supplement of isoflavones on cognitive function in postmenopausal women. DESIGN: Participants for this 6-month, double-blind, randomized, placebo-controlled clinical trial were women who were in good health, were postmenopausal at least 2 years, and were not using estrogen replacement therapy. Between July 24, 2000, and October 31, 2000, 56 women aged 55 to 74 years were randomized; 2 in the placebo group and 1 in the active treatment group did not complete the 6-month evaluation, and none withdrew because of adverse effects. Women randomized to active treatment (n = 27) took two pills per day, each containing 55 mg of soy-extracted isoflavones (110 mg total isoflavones per day; Healthy Woman: Soy Menopause Supplement, Personal Products Company, McNeil-PPC Inc., Skillman, NJ, USA). Women assigned to placebo (n = 26) took two identical-appearing pills per day containing inert ingredients. Cognitive function tests administered at baseline and follow-up included the following: Trails A and B, category fluency, and logical memory and recall (a paragraph recall test assessing immediate and delayed verbal memory). RESULTS: At baseline, all women were cognitively intact; there were no significant differences by treatment assignment in age, education, depressed mood, or cognitive function (all P values > 0.10). Compliance was 98% and 97%, respectively, in the placebo and treatment groups; all women took at least 85% of their pills. The women in the treatment group did consistently better, both as compared with their own baseline scores and as compared with the placebo group responses at 6 months. Comparisons of percentage change in cognitive function between baseline and follow-up showed greater improvement in category fluency for women on active treatment as compared with the case of those on placebo (P = 0.02) and showed (nonsignificantly) greater improvement on the two other tests of verbal memory and Trails B. CONCLUSION: These results suggest that isoflavone supplementation has a favorable effect on cognitive function, particularly verbal memory, in postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Age_Factors_MeSH M_Aged_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Dietary_Supplements_MeSH M_Double-Blind_Method_MeSH M_Estrogens__Non-Steroidal_MeSH S_pharmacology_MeSH Estrogens__Non-Steroidal_pharmacology_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Isoflavones_MeSH S_pharmacology_MeSH Isoflavones_pharmacology_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Mental_Recall_MeSH S_drug_effects_MeSH Mental_Recall_drug_effects_MeSH M_Middle_Aged_MeSH P_Phytotherapy_MeSH M_Plant_Extracts_MeSH S_pharmacology_MeSH Plant_Extracts_pharmacology_MeSH S_therapeutic_use_MeSH Plant_Extracts_therapeutic_use_MeSH M_Postmenopause_MeSH M_Psychiatric_Status_Rating_Scales_MeSH P_Soybeans_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH 
****** 12792297
----K I
----T Effect of low-dose transdermal E2/NETA on the reduction of postmenopausal bone loss in women.
----A OBJECTIVE: To assess the efficacy of a continuous-combined transdermal patch (estradiol/ norethisterone acetate [E(2)/NETA] 25/125; Estragest TTS, Novartis, Basel, Switzerland) in the reduction of bone loss in postmenopausal women. DESIGN: In a 96-week, double-blind, randomized, multicenter, parallel study, 124 healthy women with an intact uterus more than 4 years after menopause received either transdermal continuous-combined E(2)/NETA (0.025/0.125 mg/day) or placebo patch for 24 treatment cycles; diet was normalized for calcium intake. Lumbar spine bone mineral density (BMD) ranged from 0.969 to 0.805 g/cm2 with a mean annual BMD decrement ranging from 3% to 8% within the last 24 months. BMD at lumbar spine L(2)-L(4) (postero-anterior) and femur were assessed by dual energy x-ray absorptiometry after 6, 12, and 24 cycles. Efficacy variables included measurement of biochemical markers of bone turnover (3, 6, 12, and 24 months). RESULTS: BMD at lumbar spine was significantly higher at all time points in the E(2)/NETA group than in the placebo group (P < 0.0001). Significant increases in BMD (P < 0.0008) from baseline were observed at all sites after 24 months in the E(2)/NETA group compared with placebo, which demonstrated a decrease from baseline. At endpoint, statistically significant decrements in the values of bone remodeling markers were observed (P < 0.05) with E(2)/NETA. CONCLUSIONS: E(2)/NETA 25/125 Estragest TTS was more effective than placebo in reducing the activation frequency of bone remodeling and in preventing bone loss at the spine and hip. Effects on the hip were similar to those observed for higher doses of estrogen.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Femur_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12798527
----K E
----T A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients.
----A OBJECTIVE: Phytoestrogens are popular in treatment of menopause, although scientific evidence is insufficient as to their efficacy. We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer. METHODS: Sixty-two postmenopausal symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were reversed after a 2-month washout period. Fifty-six women completed the study. Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale, and working capacity and mood changes were assessed via validated questionnaires. In addition, we followed the levels of phytoestrogens, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone-binding globulin. Liver enzymes and creatinine were also assessed at each visit. RESULTS: The phytoestrogen regimen raised the circulating levels of phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index was reduced by 4.2 +/- 9.6 (mean +/- standard deviation) (15.5%) during phytoestrogen use and similarly by 4.0 +/- 8.1 (14.7%) during placebo use (P nonsignificant). The quality of life parameters (working capacity, mood changes) were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes, creatinine, body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported no preference (nonsignificant). CONCLUSION: Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M P_Breast_Neoplasms_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogens__Non-Steroidal_MeSH S_blood_MeSH Estrogens__Non-Steroidal_blood_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH P_Isoflavones_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Plant_Preparations_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Quality_of_Life_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12818462
----K I
----T Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy.
----A OBJECTIVES: Previous studies indicate that low-dose hormone replacement therapy (LD-HRT) can relieve vasomotor symptoms and prevent spine bone loss. METHODS: In the present study, we evaluated the effects of a low dose of conjugated equine estrogens (CEE; 0.3 mg) associated with different progestins in continuous combined scheme [2.5 mg of medroxyprogesterone acetate (n=25), 5 mg dydrogesterone (n=27), 2.5 mg nomegestrol (n=11)] as single group, on femur bone mineral density (BMD) and bone metabolism in young postmenopausal women (<or=56 years). All women were supplemented with 1 g of calcium per day, and compared with women treated with 1 g of calcium per day alone (control group, n=15). There were no significant differences in age, body mass index (BMI), hormone values, bone metabolism markers and femur BMD in the treatment and control groups before the study. RESULTS: In calcium-treated women serum plasma osteocalcin (BGP) and hydroxyproline/creatinine urinary excretion (OHP/Cr) remained stable during all the observation period. In this group, femoral neck, Ward's triangle and trochanter BMD showed a progressive and significant (P<0.05) decrease. In the LD-HRT group, a significant (P<0.05) decrease in serum BGP and OHP/Cr was observed. In these women, the values of these markers of bone turnover at 36 months were significantly (P<0.01) different from those of calcium-treated women. During the LD-HRT administration, all BMD measures did not show any significant modifications. In these women, treated with LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women in all the femur sites of measurements. In the control group, BMI significantly (P<0.05) increased from baseline value with a weight gain of 3%, while in the LD-HRT group, BMI did not change after 36 months of treatment and the 1.3% gain in body weight was not significant. LD-HRT was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile, and minimal side effects. CONCLUSION: LD-HRT was effective in reducing menopausal clinical symptoms and minimal and transient side effects were reported. In addition, the 0.30 mg/day of CEE, in addition to a proper calcium supplementation, irrespective of the progestin used, can provide effective protection against activation of bone turnover and femur osteopenia.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Drug_Therapy__Combination_MeSH M_Dydrogesterone_MeSH S_therapeutic_use_MeSH Dydrogesterone_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Femur_MeSH M_Human_MeSH M_Megestrol_MeSH S_analogs_&_derivatives_MeSH Megestrol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Megestrol_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Prospective_Studies_MeSH 
****** 12841882
----K I
----T Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms.
----A OBJECTIVE: To compare a novel vaginal ring releasing estradiol acetate (Menoring; Galen Holdings) with oral estradiol for relief of moderate to severe vasomotor symptoms in healthy postmenopausal women. DESIGN: This was a prospective, double-blind, multicenter, randomized, parallel-group study. METHOD: Women (n = 159) aged < 65 years experiencing >or= 20 hot flushes/night sweats per week received either a vaginal ring releasing estradiol acetate at a rate equivalent to 50 microg/day estradiol plus placebo tablets or oral estradiol 1 mg/day plus a placebo vaginal ring for 24 weeks. For patients with inadequate control of symptoms, the dosage was doubled at 12 weeks. A 24-week, open-label extension of the vaginal ring treatment followed double-blind treatment. RESULTS: The frequency of hot flushes/night sweats was significantly reduced (p < 0.001) in both groups at 12 and 24 weeks from baseline, by 84% and 94% for the vaginal ring group and by 73% and 83% for the oral group, respectively. The mean intensity of urogenital symptoms decreased from screening to the end of treatment in both groups. The incidence of adverse events was similar for both groups. No clinically relevant local effects of the vaginal ring were observed. CONCLUSIONS: The vaginal ring relieved both systemic and urogenital symptoms and was well tolerated and accepted. Overall, the efficacy, safety and acceptability of the vaginal ring were comparable with those of oral estradiol therapy.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Administration__Oral_MeSH M_Adult_MeSH M_Double-Blind_Method_MeSH M_England_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Prospective_Studies_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 12843161
----K E
----T Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment.
----A Long-term glucocorticoid therapy in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone. We tested the effect of two androgens, testosterone and its minimally aromatizable analog nandrolone, on muscle mass (dual x-ray absorptiometry), muscle strength (knee flexion and extension by isokinetic dynamometry), bone mineral density (BMD), and quality of life (Qualeffo-41 questionnaire) in 51 men on a mean daily prednisone dose of 12.6 +/- 2.2 mg. Men were randomized, double blind, to testosterone (200 mg mixed esters), nandrolone decanoate (200 mg), or placebo given every fortnight by im injection for 12 months. At 12 months, both androgens increased muscle mass (mean change from baseline +3.5%, +5.8%, and -0.9% in testosterone, nandrolone, and placebo groups, respectively, P < 0.0001) and muscle strength (P < 0.05). Lumbar spine BMD increased significantly only in men treated with testosterone (4.7 +/- 1.1%, P < 0.01). There was no significant change in hip or total body BMD. Testosterone, but not nandrolone or placebo, improved overall quality of life (P < 0.001). These results suggest that androgen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for androgen action on bone but not on muscle.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Anabolic_Agents_MeSH S_administration_&_dosage_MeSH Anabolic_Agents_administration_&_dosage_MeSH S_adverse_effects_MeSH Anabolic_Agents_adverse_effects_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Drug_Interactions_MeSH M_Glucocorticoids_MeSH S_adverse_effects_MeSH Glucocorticoids_adverse_effects_MeSH M_Gonadal_Steroid_Hormones_MeSH S_administration_&_dosage_MeSH Gonadal_Steroid_Hormones_administration_&_dosage_MeSH S_adverse_effects_MeSH Gonadal_Steroid_Hormones_adverse_effects_MeSH S_blood_MeSH Gonadal_Steroid_Hormones_blood_MeSH M_Human_MeSH M_Lumbar_Vertebrae_MeSH S_drug_effects_MeSH Lumbar_Vertebrae_drug_effects_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Muscle_Contraction_MeSH S_drug_effects_MeSH Muscle_Contraction_drug_effects_MeSH M_Muscle__Skeletal_MeSH S_anatomy_&_histology_MeSH Muscle__Skeletal_anatomy_&_histology_MeSH S_drug_effects_MeSH Muscle__Skeletal_drug_effects_MeSH M_Nandrolone_MeSH S_administration_&_dosage_MeSH Nandrolone_administration_&_dosage_MeSH S_adverse_effects_MeSH Nandrolone_adverse_effects_MeSH M_Placebos_MeSH M_Prednisone_MeSH S_adverse_effects_MeSH Prednisone_adverse_effects_MeSH M_Quality_of_Life_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_adverse_effects_MeSH Testosterone_adverse_effects_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12844276
----K E
----T [The effects of hormone replacement therapy in menopause on symptoms of anxiety and depression]
----A OBJECTIVE: Replacement of deficient hormones (hormone replacement therapy, HRT) is the main treatment modality in menopause. There is no concensus among researchers as to how HRT influences psychiatric symptoms that might develop during menopausal period. In this study we aimed to explore the effects of HRT on symptoms of anxiety and depression comparatively by using either estrogen or tibolone. METHOD: Women with natural menopause who applied to the outpatient Clinic of Obstetrics and Gynecology Department were included in the study. Subjects (n=70) were randomized into two groups with one group to receive 17beta-estradiol and other group tibolon. All subjects were evaluated at baseline and after 3-months of HRT with Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale (HDRS). RESULTS: Forty six of 70 patients completed the study. The 17beta-estradiol (n=23) and the tibolone (n=23) groups were similar with respect to age, education and occupational status. The time from onset of menopause was longer in the tibolon group. HARS and HDRS scores were significantly decreased after 3 months of HRT in both the 17beta-estradiol and the tibolone groups. The two drug regimens were not significantly different in this respect. CONCLUSION: HRT with 17beta-estradiol and tibolone improves symptoms of anxiety and depression in menopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Anxiety_MeSH S_drug_therapy_MeSH Anxiety_drug_therapy_MeSH M_Depression_MeSH S_drug_therapy_MeSH Depression_drug_therapy_MeSH M_English_Abstract_MeSH M_Estradiol_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Manifest_Anxiety_Scale_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Norpregnenes_MeSH S_therapeutic_use_MeSH Norpregnenes_therapeutic_use_MeSH M_Treatment_Outcome_MeSH 
****** 12846271
----K E
----T Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women.
----A BACKGROUND: After the menopause, estrogen synthesis from androgens and androgen precursors by aromatase is the main source of circulating estrogens. AIM: To evaluate whether aromatase gene (CYP19)polymorphism affects circulating estradiol (E2) levels, bone mineral density (BMD), BMD change or fracture risk. METHODS: A 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. BMD was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The polymorphism (intron 4 TTTA repeat) of CYP19 was evaluated after PCR amplification of the polymorphic site. CYP19 polymorphism was divided into three repeat groups: short (length of 7 or 8 in both alleles; n = 135), long (length of 11 or higher in both alleles; n = 47), and medium (rest of the values; n = 149). RESULTS: Of the baseline characteristics, only physical activity was associated with CYP19 polymorphism (P = 0.04) and a borderline significance was observed with previous fractures (P = 0.05). In the HRT or non-HRT groups, the 5-year serum E2 change was not associated with CYP19 polymorphism (P = 0.87 and 0.74, respectively). Further, the polymorphism did not influence the calculated annual changes of lumbar or femoral neck BMD during the 5-year follow-up in the HRT (P = 0.60 and 0.17, respectively) or non-HRT (P = 0.92 and 0.80, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. The CYP19 polymorphism was not significantly associated with fracture risk (P = 0.89 and 0.23 respectively; Cox proportional hazards model) in the HRT or non-HRT groups. CONCLUSIONS: CYP19 polymorphism was not associated with circulating E2 levels, BMD values, or fracture risk in these early postmenopausal Finnish women. If such an association exists in women, it may become apparent in older age groups.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aromatase_MeSH S_genetics_MeSH Aromatase_genetics_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH S_genetics_MeSH Bone_Density_genetics_MeSH M_Cholecalciferol_MeSH S_therapeutic_use_MeSH Cholecalciferol_therapeutic_use_MeSH M_Cyproterone_MeSH S_therapeutic_use_MeSH Cyproterone_therapeutic_use_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_blood_MeSH Estradiol_blood_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Follow-Up_Studies_MeSH P_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH M_Genotype_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH P_Polymorphism_(Genetics)_MeSH M_Postmenopause_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12851275
----K E
----T Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial.
----A CONTEXT: Clinical trials demonstrating increased risk of cardiovascular disease and breast cancer among women randomized to hormone replacement therapy have increased interest in other therapies for menopausal symptoms. Dietary supplements containing isoflavones are widely used as alternatives to hormonal therapies for hot flashes, but there is a paucity of data supporting their efficacy. OBJECTIVE: To compare the efficacy and safety of 2 dietary supplements derived from red clover with placebo in symptomatic menopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of menopausal women, aged 45 to 60 years, who were experiencing at least 35 hot flashes per week. The study was conducted between November 1999 and March 2001 at 3 US medical centers and included women who were recently postmenopausal (mean [SD], 3.3 [4.5] years since menopause) experiencing 8.1 hot flashes per day. Women were excluded if they were vegetarians, consumed soy products more than once per week, or took medications affecting isoflavone absorption. INTERVENTION: After a 2-week placebo run-in, 252 participants were randomly assigned to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total isoflavones per day), or an identical placebo, and followed-up for 12 weeks. MAIN OUTCOME MEASURE: The primary outcome measure was the change in frequency of hot flashes measured by participant daily diaries. Secondary outcome measures included changes in quality of life and adverse events. RESULTS: Of 252 participants, 246 (98%) completed the 12-week protocol. The reductions in mean daily hot flash count at 12 weeks were similar for the Promensil (5.1), Rimostil (5.4), and placebo (5.0) groups. In comparison with the placebo group, participants in the Promensil group (41%; 95% confidence interval [CI], 29%-51%; P =.03), but not in the Rimostil group (34%; 95% CI, 22%-46%; P =.74) reduced hot flashes more rapidly. Quality-of-life improvements and adverse events were comparable in the 3 groups. CONCLUSION: Although the study provides some evidence for a biological effect of Promensil, neither supplement had a clinically important effect on hot flashes or other symptoms of menopause.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Comparative_Study_MeSH P_Dietary_Supplements_MeSH M_Double-Blind_Method_MeSH M_Estrogens__Non-Steroidal_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Isoflavones_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Menopause_MeSH S_drug_effects_MeSH Menopause_drug_effects_MeSH M_Middle_Aged_MeSH M_Plant_Extracts_MeSH S_therapeutic_use_MeSH Plant_Extracts_therapeutic_use_MeSH M_Plant_Preparations_MeSH M_Postmenopause_MeSH S_drug_effects_MeSH Postmenopause_drug_effects_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH P_Trifolium_MeSH 
****** 12851519
----K E
----T Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.
----A OBJECTIVE: Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. DESIGN: To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. RESULTS: Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. CONCLUSIONS: This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Attention_MeSH S_drug_effects_MeSH Attention_drug_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Estrogens__Non-Steroidal_MeSH S_therapeutic_use_MeSH Estrogens__Non-Steroidal_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Isoflavones_MeSH S_therapeutic_use_MeSH Isoflavones_therapeutic_use_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Mental_Recall_MeSH S_drug_effects_MeSH Mental_Recall_drug_effects_MeSH M_Middle_Aged_MeSH M_Neuropsychological_Tests_MeSH P_Phytotherapy_MeSH M_Plant_Preparations_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH P_Pueraria_MeSH M_Questionnaires_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12850609
----K E
----T Breathing during sleep in menopause: a randomized, controlled, crossover trial with estrogen therapy.
----A OBJECTIVE: To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. METHODS: A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P <.05. RESULTS: The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P =.047) and frequency (P =.049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. CONCLUSION: Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Comparative_Study_MeSH M_Cross-Over_Studies_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Incidence_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Polysomnography_MeSH S_methods_MeSH Polysomnography_methods_MeSH M_Probability_MeSH M_Prospective_Studies_MeSH M_Reference_Values_MeSH M_Respiration_MeSH S_drug_effects_MeSH Respiration_drug_effects_MeSH M_Risk_Factors_MeSH M_Sleep_MeSH S_drug_effects_MeSH Sleep_drug_effects_MeSH S_physiology_MeSH Sleep_physiology_MeSH M_Sleep_Apnea_Syndromes_MeSH S_diagnosis_MeSH Sleep_Apnea_Syndromes_diagnosis_MeSH S_epidemiology_MeSH Sleep_Apnea_Syndromes_epidemiology_MeSH M_Sleep_Disorders_MeSH S_diagnosis_MeSH Sleep_Disorders_diagnosis_MeSH S_epidemiology_MeSH Sleep_Disorders_epidemiology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12867796
----K E
----T Management of osteoporosis in patients with gastrointestinal diseases.
----A Osteoporosis is a frequent complication in the course of various gastrointestinal disorders. Since its pathogenesis is complex, and incompletely understood in comparison to the well-known pathomechanism of postmenopausal osteoporosis, adequate management is difficult. We first summarize those therapeutic options which have strong evidence in postmenopausal osteoporosis and, thereafter, we review those in the context of different gastrointestinal diseases. Treatment of the underlying intestinal disorder seems to be most important to normalise altered bone metabolism and to prevent osteoporosis in patients with coeliac disease. In patients with osteoporosis associated with Crohn's disease, various treatment strategies (such as vitamin D, sodium fluoride, bisphosphonates) are discussed. In contrast to postmenopausal osteoporosis, interventional studies in secondary osteoporosis are often limited by the small study population and data about the efficacy of any treatment in prevention of fractures are therefore lacking. Well-conducted, controlled studies with the endpoint of preventing fractures are therefore required to optimise the treatment of osteoporosis in these patients.
----P Journal_Article Review Review__Tutorial 
----M M_Bone_and_Bones_MeSH S_drug_effects_MeSH Bone_and_Bones_drug_effects_MeSH M_Calcitonin_MeSH S_administration_&_dosage_MeSH Calcitonin_administration_&_dosage_MeSH M_Calcium_MeSH S_administration_&_dosage_MeSH Calcium_administration_&_dosage_MeSH M_Celiac_Disease_MeSH S_complications_MeSH Celiac_Disease_complications_MeSH S_drug_therapy_MeSH Celiac_Disease_drug_therapy_MeSH M_Dietary_Supplements_MeSH M_Diphosphonates_MeSH S_therapeutic_use_MeSH Diphosphonates_therapeutic_use_MeSH M_Female_MeSH M_Gastrectomy_MeSH S_adverse_effects_MeSH Gastrectomy_adverse_effects_MeSH M_Gastrointestinal_Diseases_MeSH S_complications_MeSH Gastrointestinal_Diseases_complications_MeSH M_Hormone_Replacement_Therapy_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Inflammatory_Bowel_Diseases_MeSH S_complications_MeSH Inflammatory_Bowel_Diseases_complications_MeSH S_drug_therapy_MeSH Inflammatory_Bowel_Diseases_drug_therapy_MeSH M_Male_MeSH M_Osteoporosis_MeSH S_complications_MeSH Osteoporosis_complications_MeSH S_diet_therapy_MeSH Osteoporosis_diet_therapy_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH M_Sodium_Fluoride_MeSH S_therapeutic_use_MeSH Sodium_Fluoride_therapeutic_use_MeSH M_Vitamin_D_MeSH S_administration_&_dosage_MeSH Vitamin_D_administration_&_dosage_MeSH 
****** 12875727
----K E
----T A comparison of two different dosages of conjugated equine estrogen in continuous combined hormone replacement therapy with progestin.
----A OBJECTIVE: To investigate the effects of two different dosages of conjugated equine estrogen (CEE) on preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause. METHODS: A total of 236 postmenopausal women were randomly allocated to one of the following groups: Group A: 0.625 mg CEE + 2 mg medroxyprogesterone acetate (MPA) + 1 tab Caltrate-D per day; Group B: 0.3 mg CEE + 2 mg MPA + 1 tab Caltrate-D per day; Group C: 1 tab Caltrate-D per day as the control group. The study was continued for 2 years.The following parameters were monitored: (1) L2-4 bone mineral density (BMD) (measured with dual energy X-ray absorptiometry (DEX)), (2) menopausal syndrome improvement (assessed by comparing Kupperman scores), (3) vaginal bleeding rate, and the thickness of the endometrium and breast in each group. RESULTS: Overall, 213 cases (90%) completed the 1-year study and 176 cases (75%) completed the 2-year study. The percentage changes in L2-4 BMD at the 12th and 24th month in Group A were +2.3% and +3.7%, respectively, with the posttreatment values being significantly higher than pretreatment values (P < 0.001). The percentage changes were +2.7% at 12th month (P < 0.05) and +0.7% at 24th month (P > 0.05) in Group B. And that of Group C were -0.4% at 12th month and -1.6% at 24th month (P > 0.05). L2-4 BMD in both Group A and B was significantly higher than that in Group C at 12th and 24th month (A vs C, P < 0.001; B vs C, P < 0.05). Kupperman Scores were significantly reduced after 1, 3, 6, 12 and 24 months in all 3 groups when compared with baseline (P < 0.001). Scores in Group A and Group B were significantly lower than that in Group C (P < 0.001). However, the vaginal bleeding rates in Group A were significantly higher than that in Group B or in Group C. There was no atypical hyperplasia of endometrium in the 3 groups by the end of the study. One patient in Group A developed superficial thrombophlebitis by the end of 12th month. CONCLUSION: Continuous combination of CEE and MPA is effective in preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause. The vaginal bleeding rates in the Group treated with 0.625 mg/d CEE were significantly higher than those treated with 0.3 mg/d CEE.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Alkaline_Phosphatase_MeSH S_blood_MeSH Alkaline_Phosphatase_blood_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Comparative_Study_MeSH M_Endometrium_MeSH S_pathology_MeSH Endometrium_pathology_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH S_adverse_effects_MeSH Hormone_Replacement_Therapy_adverse_effects_MeSH S_methods_MeSH Hormone_Replacement_Therapy_methods_MeSH M_Human_MeSH M_Menopause_MeSH M_Middle_Aged_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH M_Uterine_Hemorrhage_MeSH S_epidemiology_MeSH Uterine_Hemorrhage_epidemiology_MeSH 
****** 12911187
----K E
----T Analysis of 1-year vertebral fracture risk reduction data in treatments for osteoporosis.
----A One-year vertebral fracture risk reduction from clinical trials in adults with postmenopausal or glucocorticoid-induced osteoporosis is reviewed. Data were obtained by conducting a literature search of osteoporosis medications using the MEDLINE database, bibliographies of selected citations, and recent meeting abstracts. The methodologic quality of the trials was assessed using recently published criteria for ranking evidence. In prospective analyses, the 1-year risk of new morphometric vertebral fractures was reduced by risedronate 5 mg/d in two 3-year studies in postmenopausal women with prevalent vertebral fracture, and in two 1-year studies in patients with or at risk for glucocorticoid-induced osteoporosis. The 1-year risk of clinical vertebral fractures was reduced by alendronate and raloxifene in post hoc analyses. Reduction of morphometrically identified vertebral fracture risk is a more stringent therapeutic goal than clinical vertebral fracture risk. Therefore, more weight should be given to data from studies that use the morphometry to assess vertebral fracture incidence.
----P Journal_Article Review Review__Academic 
----M M_Adult_MeSH M_Clinical_Trials_MeSH M_Female_MeSH M_Human_MeSH M_Male_MeSH M_Osteoporosis_MeSH S_complications_MeSH Osteoporosis_complications_MeSH S_therapy_MeSH Osteoporosis_therapy_MeSH P_Risk_Reduction_Behavior_MeSH M_Spinal_Fractures_MeSH S_etiology_MeSH Spinal_Fractures_etiology_MeSH S_prevention_&_control_MeSH Spinal_Fractures_prevention_&_control_MeSH M_Time_Factors_MeSH 
****** 12911449
----K I
----T Effect of combined oral estrogen/progestogen preparation (Kliogest) on bone mineral density, plasma lipids and postmenopausal symptoms in HRT-naive Thai women.
----A BACKGROUND: Kliogest is commonly prescribed for the relief of acute postmenopausal symptoms and prevention of postmenopausal bone loss. However, there have been few data on its effect in Asian women. METHODS: This 1-year, single-center, randomized, double-blind and placebo-controlled study evaluated the efficacy and safety of Kliogest in hormone replacement therapy (HRT)-naive Thai women. The subjects were 120 healthy Thai women aged between 45 and 65 years, with intact uterus, and who had been amenorrheic for at least 1 year. RESULTS: Kliogest increased spine (+ 6%, p < 0.01) and hip (+2%, p < 0.01) bone mineral density (BMD), and lowered plasma total cholesterol (TC) (-16%, p < 0.05) and low density lipoprotein cholesterol (LDL-C) (-16%, p < 0.05) concentrations. However, Kliogest also resulted in a decrease in high density lipoprotein cholesterol (HDL-C) concentration (-18%, p < 0.05). Compared to placebo, the reduction in menopausal symptoms by Kliogest was not statistically significant. The frequency and severity of treatment-related uterine bleeding decreased with the duration of Kliogest treatment. Furthermore, there was a fairly strong relationship between the change in serum estrone concentration and the average monthly weighted bleeding scores over the first 6 months (Spearman's correlation r = 0.54; p < 0.001), which became weaker over the entire treatment period (Spearman's correlation r = 0.27; p < 0.01). Although there was a small to moderate relationship between baseline estrone concentration and both lumbar (r = 0.23, p < 0.02) and hip (r = 0.20, p < 0.05) BMD, there was no significant relationship between Kliogest-induced change in estrone concentration and change in lumbar and hip BMD. CONCLUSIONS: Continuous treatment with Kliogest for 1 year reversed the potential postmenopausal bone loss in HRT-naive Thai postmenopausal women. However, its effect on cardiovascular risk is uncertain. Furthermore, Kliogest is safe but appears to have no significant effect on climacteric symptoms in the patients in the present study.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Oral_MeSH M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH M_Double-Blind_Method_MeSH M_Drug_Combinations_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Estriol_MeSH S_administration_&_dosage_MeSH Estriol_administration_&_dosage_MeSH S_pharmacology_MeSH Estriol_pharmacology_MeSH S_therapeutic_use_MeSH Estriol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_administration_&_dosage_MeSH Estrogens_administration_&_dosage_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH S_drug_effects_MeSH Lipoproteins__HDL_Cholesterol_drug_effects_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH S_drug_effects_MeSH Lipoproteins__LDL_Cholesterol_drug_effects_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_administration_&_dosage_MeSH Norethindrone_administration_&_dosage_MeSH S_analogs_&_derivatives_MeSH Norethindrone_analogs_&_derivatives_MeSH S_pharmacology_MeSH Norethindrone_pharmacology_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH M_Progestins_MeSH S_administration_&_dosage_MeSH Progestins_administration_&_dosage_MeSH M_Support__Non-U_S__Gov't_MeSH M_Thailand_MeSH M_Treatment_Outcome_MeSH M_Uterine_Hemorrhage_MeSH 
****** 12915650
----K E
----T Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea.
----A This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Adolescent_MeSH M_Adult_MeSH M_Amenorrhea_MeSH S_complications_MeSH Amenorrhea_complications_MeSH S_metabolism_MeSH Amenorrhea_metabolism_MeSH M_Biological_Markers_MeSH M_Bone_Diseases__Metabolic_MeSH S_drug_therapy_MeSH Bone_Diseases__Metabolic_drug_therapy_MeSH S_etiology_MeSH Bone_Diseases__Metabolic_etiology_MeSH S_metabolism_MeSH Bone_Diseases__Metabolic_metabolism_MeSH M_Bone_Resorption_MeSH S_metabolism_MeSH Bone_Resorption_metabolism_MeSH M_Bone_and_Bones_MeSH S_drug_effects_MeSH Bone_and_Bones_drug_effects_MeSH S_metabolism_MeSH Bone_and_Bones_metabolism_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Contraceptives__Oral__Combined_MeSH S_adverse_effects_MeSH Contraceptives__Oral__Combined_adverse_effects_MeSH S_therapeutic_use_MeSH Contraceptives__Oral__Combined_therapeutic_use_MeSH M_Double-Blind_Method_MeSH M_Ethinyl_Estradiol_MeSH S_adverse_effects_MeSH Ethinyl_Estradiol_adverse_effects_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Gonadal_Steroid_Hormones_MeSH S_blood_MeSH Gonadal_Steroid_Hormones_blood_MeSH M_Human_MeSH M_Hypothalamic_Diseases_MeSH S_complications_MeSH Hypothalamic_Diseases_complications_MeSH S_metabolism_MeSH Hypothalamic_Diseases_metabolism_MeSH M_Norgestrel_MeSH S_adverse_effects_MeSH Norgestrel_adverse_effects_MeSH S_analogs_&_derivatives_MeSH Norgestrel_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Norgestrel_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12916291
----K E
----T Hormone replacement therapy for postmenopausal osteoporosis.
----A The role of HRT for the prevention of osteoporosis has been clarified by the recent results of the WHI. There is consistent and favorable data from RCTs supporting the efficacy of HRT on the surrogate outcome of bone density at both cortical and trabecular sites, including a dose-response relationship. Both observational and RCT data provide support that HRT has a positive impact on the reduction of vertebral and hip fractures. The unfavorable risk/benefit profile of HRT, however, strongly limits its use for prevention of osteoporosis, given that there are other medications that have demonstrated fracture efficacy.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Female_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH 
****** 12916293
----K E
----T Bisphosphonate treatment of osteoporosis.
----A Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.
----P Journal_Article Review Review_Literature 
----M M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Clinical_Trials_MeSH M_Diphosphonates_MeSH S_therapeutic_use_MeSH Diphosphonates_therapeutic_use_MeSH M_Human_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH 
****** 12916294
----K E
----T The anabolic effects of parathyroid hormone therapy.
----A PTH represents an important new advance in the therapy of osteoporosis. As an anabolic agent, its potential might be substantially greater than that of antiresorptive agents. Clear evidence in human trials now documents the ability of PTH to stimulate cancellous bone formation and to reduce fractures. Because antiresorptive agents and PTH work by distinct mechanisms of action, it is possible that the combination of these agents could be significantly more potent than either agent alone. There are other unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. In addition, more large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. More information is also required to determine the possible need for antiresorptive therapy after PTH. Protocols to consider PTH as an intermittent recycling therapy would be of interest. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al [78] have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Ultimately, when the anabolic and catabolic mechanisms of PTH can be clearly distinguished, both mechanistically and in molecular terms, it may be possible to develop PTH analogs that are more purely anabolic.
----P Journal_Article Review Review__Tutorial 
----M M_Animals_MeSH M_Clinical_Trials_MeSH M_Drug_Therapy__Combination_MeSH M_Female_MeSH M_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Male_MeSH M_Osteoporosis_MeSH S_drug_therapy_MeSH Osteoporosis_drug_therapy_MeSH S_metabolism_MeSH Osteoporosis_metabolism_MeSH M_Parathyroid_Hormone_MeSH S_pharmacology_MeSH Parathyroid_Hormone_pharmacology_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12941676
----K I
----T Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.
----A CONTEXT: Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE: To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION: Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES: The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS: Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study. CONCLUSIONS: In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Biological_Markers_MeSH S_analysis_MeSH Biological_Markers_analysis_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Bone_Remodeling_MeSH S_drug_effects_MeSH Bone_Remodeling_drug_effects_MeSH M_Densitometry__X-Ray_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Osteoporosis__Postmenopausal_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 12943477
----K E
----T An economic analysis of hormone replacement therapy for the prevention of fracture in young postmenopausal women.
----A Osteoporosis is a major public health problem that will become increasingly important as our population ages. It leads to fractures that deeply affect the patients' quality of life. Osteoporosis is recognised as a leading factor in healthcare cost worldwide. For years, experts have recommended hormone replacement therapy (HRT), consisting of oestrogen with or without progestin, as the first-line therapy to prevent bone loss in postmenopausal women. Recently published randomised, controlled trials and well-designed meta-analyses confirm that HRT has both advantages and disadvantages. The advantages include prevention of osteoporotic fractures and colorectal cancer. The disadvantages are the resulting adverse effects such as coronary artery disease, stroke, thromboembolic events, breast cancer and cholecystitis. In the light of these findings, medical associations recommend against the routine use of oestrogen and progestin for the prevention of chronic conditions in postmenopausal women. HRT, administered for the prevention of fractures in all young postmenopausal women, would have an additional cost/year of life gained that is too expensive. However, this strategy seems to be cost-effective when young postmenopausal women at high risk for fractures are selected. Even if this strategy seems attractive, the adverse effects of HRT are not acceptable. This situation implies that other treatments must be found to prevent or treat osteoporosis. Among them, calcium and vitamin D were shown to be cost-saving in osteoporosis and even costs-effective in osteopoenia in young postmenopausal women.
----P Journal_Article Review Review__Tutorial 
----M M_Age_Factors_MeSH M_Cost-Benefit_Analysis_MeSH M_Estrogen_Replacement_Therapy_MeSH S_economics_MeSH Estrogen_Replacement_Therapy_economics_MeSH M_Estrogens_MeSH S_economics_MeSH Estrogens_economics_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Fractures_MeSH S_drug_therapy_MeSH Fractures_drug_therapy_MeSH S_etiology_MeSH Fractures_etiology_MeSH S_prevention_&_control_MeSH Fractures_prevention_&_control_MeSH M_Human_MeSH M_Osteoporosis__Postmenopausal_MeSH S_complications_MeSH Osteoporosis__Postmenopausal_complications_MeSH S_drug_therapy_MeSH Osteoporosis__Postmenopausal_drug_therapy_MeSH M_Progestins_MeSH S_economics_MeSH Progestins_economics_MeSH S_therapeutic_use_MeSH Progestins_therapeutic_use_MeSH M_Randomized_Controlled_Trials_MeSH 
****** 12970273
----K E
----T Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome.
----A Hirsutism is a common and distressing symptom frequently encountered in women with polycystic ovary syndrome (PCOS), who also show relative insulin resistance. The aim of this trial, in which hirsutism was the primary end point, was to compare the efficacy of the oral antihyperglycemic medication metformin with that of an established treatment, combined ethinyl estradiol and cyproterone acetate. Patients (n = 52) were randomized to receive either metformin (500 mg, three times daily) or Dianette (ethinyl estradiol, 35 micro g; cyproterone acetate, 2 mg) treatment for 12 months, with assessments before treatment, at 6 months, and at 12 months. Both objective and subjective methods of evaluating hirsutism were used, and in addition, patient perceptions were examined. The results show that metformin is potentially an effective treatment for moderate to severe hirsutism in women with PCOS. They also suggest that in some respects (Ferriman-Gallwey score and patient self-assessment), it is more efficacious than the standard treatment (Dianette). The objective evaluation of hair diameter reduction showed that both treatments were moderately effective at multiple anatomical sites. Dianette treatment was responsible for profound suppression of androgen activity, in contrast to metformin, which induced negligible change. However, metformin did reduce markers of insulin resistance. The data suggest that hirsutism may be effectively treated by reducing hyperinsulinemia.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Acne_Vulgaris_MeSH S_complications_MeSH Acne_Vulgaris_complications_MeSH M_Androgen_Antagonists_MeSH S_therapeutic_use_MeSH Androgen_Antagonists_therapeutic_use_MeSH M_Anthropometry_MeSH M_Blood_Glucose_MeSH S_metabolism_MeSH Blood_Glucose_metabolism_MeSH M_Blood_Pressure_MeSH S_drug_effects_MeSH Blood_Pressure_drug_effects_MeSH S_physiology_MeSH Blood_Pressure_physiology_MeSH M_Body_Mass_Index_MeSH M_Comparative_Study_MeSH M_Cyproterone_Acetate_MeSH S_therapeutic_use_MeSH Cyproterone_Acetate_therapeutic_use_MeSH M_Estradiol_Congeners_MeSH S_therapeutic_use_MeSH Estradiol_Congeners_therapeutic_use_MeSH M_Ethinyl_Estradiol_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Hirsutism_MeSH S_drug_therapy_MeSH Hirsutism_drug_therapy_MeSH S_etiology_MeSH Hirsutism_etiology_MeSH M_Hormones_MeSH S_blood_MeSH Hormones_blood_MeSH M_Human_MeSH M_Hypoglycemic_Agents_MeSH S_therapeutic_use_MeSH Hypoglycemic_Agents_therapeutic_use_MeSH M_Insulin_Resistance_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Metformin_MeSH S_therapeutic_use_MeSH Metformin_therapeutic_use_MeSH M_Polycystic_Ovary_Syndrome_MeSH S_complications_MeSH Polycystic_Ovary_Syndrome_complications_MeSH M_Sebum_MeSH S_metabolism_MeSH Sebum_metabolism_MeSH 
****** 12970309
----K E
----T Effects of long-term estrogen replacement therapy versus combined hormone replacement therapy on nitric oxide-dependent vasomotor function.
----A Postmenopausal hormone replacement therapy (HRT) with estrogen may increase production of the predominant endothelium-derived vasodilator nitric oxide (NO) and consequently improve vascular reactivity. In contrast, concurrent progestin therapy may oppose this beneficial effect. We studied the effect of long-term estrogen HRT and combined HRT on vasomotor function and on plasma nitrate, which reflects the amount of NO in the circulation. As lipid peroxidation affects NO production and impairs endothelial function, we also measured the amount of the in vivo lipid peroxidation marker urinary 8-iso-prostaglandin F(2 alpha). The study group comprised 15 women receiving estradiol valerate HRT (mean age, 56 yr; treatment duration, 10.5 yr) and 15 women receiving combined HRT with estradiol valerate and levonorgestrel (mean age, 58 yr; treatment duration, 11.3 yr). The peak flow velocity (PFV) and pulsatility index of the common carotid and internal carotid artery and the abdominal aorta were measured by ultrasonography after long-term HRT (baseline), after a 4-wk pause and again 3 wk after reintroducing HRT. A statistically significant interaction between the groups and time points was observed in the PFV of the internal carotid artery (P = 0.011). In women taking estradiol valerate, the PFV values decreased significantly after withdrawal of HRT (P = 0.007) and increased again to the baseline level after reintroduction of therapy (P < 0.001). In women receiving combined HRT, the PFV remained stable over all study periods. At baseline, the PFV of women taking estradiol valerate correlated with the plasma nitrate concentration in the common carotid artery (r = 0.646; P = 0.009) and in the abdominal aorta (r = 0.579; P = 0.024). For pulsatility index and urinary 8-iso-prostaglandin F(2 alpha) excretion, there were no significant differences between the groups. Our results suggest that the favorable effects of long-term estrogen treatment on blood flow are at least partly mediated through NO. The addition of levonorgestrel to the treatment regimen appears to abolish this effect.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Aorta__Abdominal_MeSH S_drug_effects_MeSH Aorta__Abdominal_drug_effects_MeSH M_Carotid_Arteries_MeSH S_drug_effects_MeSH Carotid_Arteries_drug_effects_MeSH S_ultrasonography_MeSH Carotid_Arteries_ultrasonography_MeSH M_Comparative_Study_MeSH M_Dinoprost_MeSH S_blood_MeSH Dinoprost_blood_MeSH M_Drug_Combinations_MeSH M_Endothelium__Vascular_MeSH S_drug_effects_MeSH Endothelium__Vascular_drug_effects_MeSH S_metabolism_MeSH Endothelium__Vascular_metabolism_MeSH M_Estradiol_MeSH S_analogs_&_derivatives_MeSH Estradiol_analogs_&_derivatives_MeSH S_therapeutic_use_MeSH Estradiol_therapeutic_use_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_therapeutic_use_MeSH Estrogens_therapeutic_use_MeSH M_Female_MeSH M_Hemodynamic_Processes_MeSH S_drug_effects_MeSH Hemodynamic_Processes_drug_effects_MeSH M_Human_MeSH M_Levonorgestrel_MeSH S_therapeutic_use_MeSH Levonorgestrel_therapeutic_use_MeSH M_Lipid_Peroxidation_MeSH S_drug_effects_MeSH Lipid_Peroxidation_drug_effects_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Middle_Aged_MeSH M_Muscle__Smooth__Vascular_MeSH S_physiology_MeSH Muscle__Smooth__Vascular_physiology_MeSH S_ultrasonography_MeSH Muscle__Smooth__Vascular_ultrasonography_MeSH M_Nitric_Oxide_MeSH S_blood_MeSH Nitric_Oxide_blood_MeSH S_physiology_MeSH Nitric_Oxide_physiology_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12974172
----K E
----T Hormone replacement therapy--is there a place for its use in neurology?
----A Stroke remains the third leading cause of mortality in developed countries despite declining tendency over the past decades. As the leading cause of disability and second cause of dementia, primary prevention should be the main way to fight the disease, since therapy is not efficient enough. Several observations pointed to estrogen as a protective agent that may reduce stroke risk, however, studies have shown conflicting data. There is no strong evidence that hormone replacement therapy (HRT) increases stroke risk. Several studies have shown that HRT may reduce the risk of fatal stroke. Conflicting results have been found for Alzheimer's disease and HRT as well. An association between higher serum concentration of estradiol and decreased risk of cognitive decline has been found in some studies, supporting the hypothesis that estrogen concentration may play a significant role in brain protection. Having in mind results of recent randomized trials, it is suggested that HRT should not be recommended on general basis for the primary or secondary prevention of cardiovascular/cerebrovascular diseases or for primary prevention of degenerative diseases such as Alzheimer's disease. Osteoporosis, cognitive decline and climacteric symptoms that are likely to impact on quality of life, speak in favor for recommendation of HRT use. On the other side, family history of breast carcinoma, mastopathy, thromboembolism, in certain cases gallbladder disease, will discourage the commencement of HRT. Respecting the patient's preferences and having benefits and risks in mind as well as science advisory statements, individual counseling regarding HRT should be the leading concept in the healthcare of postmenopausal women.
----P Journal_Article Review Review__Tutorial 
----M M_Aged_MeSH M_Alzheimer_Disease_MeSH S_etiology_MeSH Alzheimer_Disease_etiology_MeSH S_prevention_&_control_MeSH Alzheimer_Disease_prevention_&_control_MeSH M_Cardiovascular_Diseases_MeSH S_etiology_MeSH Cardiovascular_Diseases_etiology_MeSH S_prevention_&_control_MeSH Cardiovascular_Diseases_prevention_&_control_MeSH M_Cerebrovascular_Accident_MeSH S_etiology_MeSH Cerebrovascular_Accident_etiology_MeSH S_prevention_&_control_MeSH Cerebrovascular_Accident_prevention_&_control_MeSH M_Female_MeSH M_Genetic_Predisposition_to_Disease_MeSH P_Hormone_Replacement_Therapy_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Neurology_MeSH S_trends_MeSH Neurology_trends_MeSH M_Patient_Care_Planning_MeSH M_Pedigree_MeSH M_Postmenopause_MeSH S_physiology_MeSH Postmenopause_physiology_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH 
****** 14509153
----K E
----T Effect of garlic on lipid profile and psychopathologic parameters in people with mild to moderate hypercholesterolemia.
----A BACKGROUND: The beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardioprotective properties. Its effect on psychopathologic parameters has never been reported. OBJECTIVE: To evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia. METHODS: In a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student's t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test. RESULTS: No significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated. CONCLUSION: Short-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Body_Weight_MeSH S_drug_effects_MeSH Body_Weight_drug_effects_MeSH M_Cholesterol_MeSH S_blood_MeSH Cholesterol_blood_MeSH P_Dietary_Supplements_MeSH M_Double-Blind_Method_MeSH M_Female_MeSH P_Garlic_MeSH M_Human_MeSH M_Hypercholesterolemia_MeSH S_blood_MeSH Hypercholesterolemia_blood_MeSH S_drug_therapy_MeSH Hypercholesterolemia_drug_therapy_MeSH S_psychology_MeSH Hypercholesterolemia_psychology_MeSH M_Lipids_MeSH S_blood_MeSH Lipids_blood_MeSH M_Lipoproteins__HDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__HDL_Cholesterol_blood_MeSH M_Lipoproteins__LDL_Cholesterol_MeSH S_blood_MeSH Lipoproteins__LDL_Cholesterol_blood_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Patient_Compliance_MeSH P_Phytotherapy_MeSH M_Psychological_Tests_MeSH M_Treatment_Outcome_MeSH M_Triglycerides_MeSH S_blood_MeSH Triglycerides_blood_MeSH 
****** 14519707
----K I
----T Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial.
----A CONTEXT: In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures. OBJECTIVE: To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years. INTERVENTION: Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURES: All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk. RESULTS: Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54). CONCLUSIONS: This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Bone_Density_MeSH S_drug_effects_MeSH Bone_Density_drug_effects_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_therapeutic_use_MeSH Estrogens__Conjugated_(USP)_therapeutic_use_MeSH M_Female_MeSH M_Fractures_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Middle_Aged_MeSH M_Osteoporosis_MeSH S_epidemiology_MeSH Osteoporosis_epidemiology_MeSH M_Postmenopause_MeSH M_Progesterone_Congeners_MeSH S_therapeutic_use_MeSH Progesterone_Congeners_therapeutic_use_MeSH M_Proportional_Hazards_Models_MeSH M_Risk_MeSH M_Support__U_S__Gov't__P_H_S__MeSH 
****** 14551014
----K I
----T Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms.
----A OBJECTIVE: To assess the efficacy, tolerability, and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol (E2), compared with placebo, for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women. METHODS: Women with moderate to severe vasomotor symptoms (seven or more per day or 56 per week average) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 (n = 113) or 100 microg per day E2 (n = 112), or a placebo vaginal ring (n = 108). Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale. Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology. Participant satisfaction with the vaginal ring was evaluated via questionnaire. RESULTS: Vasomotor symptoms significantly improved in both treatment groups, compared with placebo (P <.05). There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo. For women with vaginal atrophy at baseline (n = 60), the maturation index improved significantly in both treatment groups compared with placebo. Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups (P <.05) compared with placebo. The vaginal rings were well tolerated. Most adverse events were mild or moderate and consistent with estrogen therapy. CONCLUSION: A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms, compared with placebo. The E2 vaginal ring was well tolerated.
----P Clinical_Trial Clinical_Trial__Phase_III Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Adult_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_pathology_MeSH Hot_Flashes_pathology_MeSH M_Human_MeSH P_Menopause_MeSH M_Middle_Aged_MeSH M_Patient_Satisfaction_MeSH M_Questionnaires_MeSH M_Severity_of_Illness_Index_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_United_States_MeSH M_Urination_Disorders_MeSH S_drug_therapy_MeSH Urination_Disorders_drug_therapy_MeSH S_pathology_MeSH Urination_Disorders_pathology_MeSH 
****** 12953327
----K E
----T Transdermal delivery of sex steroids for hormone replacement therapy and contraception. A review of principles and practice.
----A The percutaneous route is an effective method for delivery of reproductive hormones. Several transdermal therapeutic systems (TTS) releasing estrogens, progestogens and androgens from patches attached to the skin are currently in clinical use. For women, transdermal systems have been developed for hormonal replacement therapy (HRT) and recently for contraception. HRT with patches releasing only estradiol (E2) should be supplemented with a progestogen to protect the endometrium. Patches simultaneously releasing both E2 and a progestogen are also available. Combined regimens are either continuous or sequential. In the latter, estrogen-only patches are applied for 14 days, followed by 14-day application of patches releasing both hormones. Transdermal HRT successfully treats menopausal symptoms and has a bone-sparing effect. Transdermal contraceptive patches deliver ethinyl E2 in combination with the progestogen norelgestromin. This system provides an effective contraceptive and acceptable bleeding pattern not different from that of oral contraceptives. The types of adverse events experienced are approximately the same as with oral contraceptives. Reactions at the application site cause about 3% women to discontinue the use of patches. Transdermal systems also have been designed to supplement testosterone in hypogonadal men. Testosterone released from patches produces positive effects on mood and sexual behavior and significantly increases bone mass. Men using testosterone patches have to be regularly monitored for an increase in prostate volume and changes in prostate-specific antigen. Reproductive steroids delivered by the skin avoid first-pass liver metabolism, typical of oral dosing; consequently, the liver tissue is affected to a lesser degree. Other advantages include rapid onset and termination of action, noninvasive self-administration and attainment of therapeutic hormone levels with low daily doses. Reduced frequency of dosing has the potential to improve patient compliance. While compliance is important for any hormone, it is particularly important for contraceptive purposes. Like oral delivery of sex steroids, percutaneous absorption is characterized by intra- and interindividual variability. New technologies under development, combining electronics and low-frequency ultrasound, have the potential to provide precise dosing as well as drug delivery "on demand."
----P Journal_Article Review Review__Tutorial 
----M M_Administration__Cutaneous_MeSH M_Contraception_MeSH S_methods_MeSH Contraception_methods_MeSH M_Contraceptive_Agents__Female_MeSH S_administration_&_dosage_MeSH Contraceptive_Agents__Female_administration_&_dosage_MeSH S_pharmacokinetics_MeSH Contraceptive_Agents__Female_pharmacokinetics_MeSH M_Contraceptives__Oral__Combined_MeSH S_administration_&_dosage_MeSH Contraceptives__Oral__Combined_administration_&_dosage_MeSH M_Drug_Administration_Schedule_MeSH M_Drug_Delivery_Systems_MeSH M_Equipment_Design_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Ethinyl_Estradiol_MeSH S_administration_&_dosage_MeSH Ethinyl_Estradiol_administration_&_dosage_MeSH M_Female_MeSH M_Gonadal_Steroid_Hormones_MeSH S_administration_&_dosage_MeSH Gonadal_Steroid_Hormones_administration_&_dosage_MeSH S_blood_MeSH Gonadal_Steroid_Hormones_blood_MeSH M_Human_MeSH M_Male_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH 
****** 14556820
----K E
----T Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.
----A OBJECTIVE: To determine whether cognitive behavior therapy (CBT) targeted to problematic attitudes common among women with functional hypothalamic amenorrhea would restore ovarian function. DESIGN: Randomized, prospective, controlled intervention. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Sixteen women participated who had functional hypothalamic amenorrhea; were of normal body weight; and did not report psychiatric conditions, eating disorders, or excessive exercise. INTERVENTION(S): Subjects were randomized to CBT or observation for 20 weeks. MAIN OUTCOME MEASURE(S): Serum levels of E(2) and P and vaginal bleeding were monitored. RESULT(S): Of eight women treated with CBT, six resumed ovulating, one had partial recovery of ovarian function without evidence of ovulation, and one did not display return of ovarian function. Of those randomized to observation, one resumed ovulating, one had partial return of ovarian function, and six did not recover. Thus, CBT resulted in a higher rate of ovarian activity (87.5%) than did observation (25.0%), chi(2) = 7.14. CONCLUSION(S): A cognitive behavioral intervention designed to minimize problematic attitudes linked to hypothalamic allostasis was more likely to result in resumption of ovarian activity than observation. The prompt ovarian response to CBT suggests that a tailored behavioral intervention offers an efficacious treatment option that also avoids the pitfalls of pharmacological modalities.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Amenorrhea_MeSH S_etiology_MeSH Amenorrhea_etiology_MeSH S_physiopathology_MeSH Amenorrhea_physiopathology_MeSH P_Cognitive_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Hypothalamic_Diseases_MeSH S_complications_MeSH Hypothalamic_Diseases_complications_MeSH S_therapy_MeSH Hypothalamic_Diseases_therapy_MeSH M_Ovary_MeSH S_physiopathology_MeSH Ovary_physiopathology_MeSH M_Ovulation_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Treatment_Outcome_MeSH 
****** 14563098
----K E
----T Assessment and treatment of hot flushes and menopausal mood disturbance.
----A More than 1 million women are expected to reach menopause each year, many of whom will experience hot flushes and other neuropsychological symptoms that may diminish their quality of life. Hot flushes are the core symptoms that reflect the brain's response to the changing hormonal milieu of the menopause transition, particularly to the rapidly fluctuating and falling levels of estradiol. The physical symptoms of hot flushes and the associated changes in sleep, mood, and cognition will lead many women to seek medical care. It is critical to understand the interrelationship of hot flushes and other neuropsychological symptoms of the menopause transition so that treatment priorities can be established. For example, if sleep disruption explains most daytime neuropsychological problems in women with hot flushes, treating insomnia should be considered a priority. Alternatively, mood, cognition, and quality of life may be disturbed independent of sleep problems. In such a situation, each symptom should be evaluated separately from any assessment of sleep. As recent data from the WHI establish the risks of long-term HRT use, concern about using HRT, even as a short-term intervention, has increased substantially. Although HRT remains the first-line treatment for hot flushes, the WHI findings have drawn attention to nonhormonal treatments of hot flushes and other menopausal symptoms. Growing evidence to support the efficacy of serotonergic antidepressants and other psychoactive medications in the treatment for hot flushes suggests that nonhormonal interventions will prove important alternatives to HRT. As further evidence of the benefits of psychoactive medications for menopausal symptoms is established, the choice between using hormonal and nonhormonal therapies for management of menopausal symptoms will continue to evolve.
----P Journal_Article Review Review__Academic 
----M M_Acetic_Acids_MeSH S_therapeutic_use_MeSH Acetic_Acids_therapeutic_use_MeSH M_Aging_MeSH M_Anti-Anxiety_Agents_MeSH S_therapeutic_use_MeSH Anti-Anxiety_Agents_therapeutic_use_MeSH M_Cognition_Disorders_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH P_Hormone_Replacement_Therapy_MeSH M_Hot_Flashes_MeSH S_blood_MeSH Hot_Flashes_blood_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH S_etiology_MeSH Hot_Flashes_etiology_MeSH M_Human_MeSH M_Menopause_MeSH S_physiology_MeSH Menopause_physiology_MeSH M_Middle_Aged_MeSH M_Mood_Disorders_MeSH S_diagnosis_MeSH Mood_Disorders_diagnosis_MeSH S_drug_therapy_MeSH Mood_Disorders_drug_therapy_MeSH M_Randomized_Controlled_Trials_MeSH M_Sleep_Disorders_MeSH 
****** 12674333
----K E
----T A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.
----A A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women.
----P Journal_Article 
----M M_Alleles_MeSH M_Bone_Density_MeSH S_genetics_MeSH Bone_Density_genetics_MeSH S_physiology_MeSH Bone_Density_physiology_MeSH M_Denmark_MeSH S_epidemiology_MeSH Denmark_epidemiology_MeSH M_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Fractures_MeSH S_enzymology_MeSH Fractures_enzymology_MeSH S_epidemiology_MeSH Fractures_epidemiology_MeSH S_genetics_MeSH Fractures_genetics_MeSH M_Gene_Frequency_MeSH M_Genotype_MeSH M_Human_MeSH M_Longitudinal_Studies_MeSH M_Methylenetetrahydrofolate_Reductase_(NADPH2)_MeSH S_genetics_MeSH Methylenetetrahydrofolate_Reductase_(NADPH2)_genetics_MeSH S_physiology_MeSH Methylenetetrahydrofolate_Reductase_(NADPH2)_physiology_MeSH M_Middle_Aged_MeSH M_Osteoporosis__Postmenopausal_MeSH S_enzymology_MeSH Osteoporosis__Postmenopausal_enzymology_MeSH S_genetics_MeSH Osteoporosis__Postmenopausal_genetics_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH P_Polymorphism_(Genetics)_MeSH M_Proportional_Hazards_Models_MeSH M_Prospective_Studies_MeSH M_Risk_Factors_MeSH M_Support__Non-U_S__Gov't_MeSH 
****** 12689685
----K E
----T Aerobic exercise and bone mineral density in middle-aged finnish men: a controlled randomized trial with reference to androgen receptor, aromatase, and estrogen receptor alpha gene polymorphisms small star, filled.
----A Our aim was to investigate associations of the polymorphic loci of androgen receptor (AR), aromatase CYP19, and estrogen receptor alpha (ERalpha) genes with bone mineral density (BMD) in a four-year controlled randomized exercise intervention trial in Finnish middle-aged men. Additionally, we studied whether the gene polymorphisms affect circulating testosterone (T), estradiol (E(2)), and sex hormone-binding globulin concentrations. The polymorphic CAG repeat of the AR gene, the TTTA repeat of the human aromatase gene, and the PvuII site of the ERalpha gene were analyzed. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with a dual-energy X-ray absorptiometry (DXA). In the exercise group, the subjects with the ERalpha gene PP or Pp genotypes showed an increase (+6.5 and +5.1%, respectively) in lumbar spine BMDs (P = 0.007; repeated measures ANOVA) during intervention, while there was no change in the subjects with the pp genotype. The long TTTA repeat (TTTA(9-12)) in aromatase gene was associated with greater height (P = 0.026) and lower BMI (P = 0.029) values than the short TTTA repeat (TTTA(6-8)). With regard to the AR gene, no statistically significant differences in bone properties were found between the genotypes. There were no significant associations of any analyzed polymorphic sites with the serum sex steroid hormone concentrations in the exercise or reference group. In conclusion, the Finnish middle-aged men with ERalpha PP or Pp genotypes appear to have increased BMD values in the lumbar spine. This increase may reflect a predisposition to age-related degenerative changes in the spine. In addition, the AR CAG repeat and aromatase TTTA repeat do not modify the effect of regular aerobic exercise on BMD.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aromatase_MeSH S_genetics_MeSH Aromatase_genetics_MeSH M_Body_Height_MeSH S_genetics_MeSH Body_Height_genetics_MeSH M_Bone_Density_MeSH S_genetics_MeSH Bone_Density_genetics_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Finland_MeSH M_Genotype_MeSH M_Human_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Polymerase_Chain_Reaction_MeSH M_Polymorphism_(Genetics)_MeSH M_Receptors__Androgen_MeSH S_physiology_MeSH Receptors__Androgen_physiology_MeSH M_Receptors__Estrogen_MeSH S_genetics_MeSH Receptors__Estrogen_genetics_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_analysis_MeSH Sex_Hormone-Binding_Globulin_analysis_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH 
****** 12826696
----K E
----T Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report.
----A This study prospectively examined changes in cognition in hypogonadal men given testosterone (T) or older hypogonadal men given dihydrotestosterone (DHT) gel. A battery of cognitive tests assessing verbal and spatial memory, language, and attention was administered at baseline (prior to medication) and again at days 90 and 180 of treatment for men receiving T gel and at baseline and days 30 and 90 of treatment for men receiving DHT gel. For men receiving T gel, circulating total T and estradiol (E(2)) were significantly raised compared with baseline, and a significant improvement in verbal memory was observed. For men receiving DHT gel, serum DHT levels increased and T levels decreased significantly compared with baseline, and a significant improvement in spatial memory was observed. The results suggest that beneficial changes in cognition can occur in hypogonadal men using T replacement levels and DHT treatment, and these changes in cognition can be reliably measured during a relative steady-state dose level. Further, our results suggest that aromatization of T to E(2) may regulate verbal memory in men, whereas nonaromatizable androgens may regulate spatial memory.
----P Clinical_Trial Journal_Article 
----M M_Adult_MeSH M_Aged_MeSH M_Androgens_MeSH S_administration_&_dosage_MeSH Androgens_administration_&_dosage_MeSH S_blood_MeSH Androgens_blood_MeSH M_Attention_MeSH S_drug_effects_MeSH Attention_drug_effects_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Dihydrotestosterone_MeSH S_administration_&_dosage_MeSH Dihydrotestosterone_administration_&_dosage_MeSH S_blood_MeSH Dihydrotestosterone_blood_MeSH M_Human_MeSH M_Hypogonadism_MeSH S_drug_therapy_MeSH Hypogonadism_drug_therapy_MeSH M_Male_MeSH M_Middle_Aged_MeSH M_Neuropsychological_Tests_MeSH M_Prospective_Studies_MeSH M_Space_Perception_MeSH S_drug_effects_MeSH Space_Perception_drug_effects_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Testosterone_MeSH S_administration_&_dosage_MeSH Testosterone_administration_&_dosage_MeSH S_blood_MeSH Testosterone_blood_MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH 
****** 12851747
----K E
----T A double-blind placebo-controlled trial on the effects of 25 mg estradiol implants on the urge syndrome in postmenopausal women.
----A The aim of this prospective double-blind randomized placebo-controlled trial was to determine the effect of systemic estrogen on the 'urge syndrome' in postmenopausal women. The trial took place in a tertiary referral urogynecology unit. Postmenopausal women with the 'urge syndrome' were randomly allocated to receive a 25 mg 17beta-estradiol implant or placebo implant. Serum estradiol levels and endometrial thickness were measured on entry to the trial and at 1, 3 and 6 months. The following outcome measures were employed: videocystourethrography, frequency volume chart, visual analogue score of symptoms, and King's Health Care Quality of life Questionnaire. Forty women were included. Subjectively there was a significant improvement in urgency in both groups and urge incontinence in the estradiol group, but no significant differences between the groups. Objectively no significant differences were demonstrated between the groups. Nine women in the estradiol group had vaginal bleeding, and 5 had a hysterectomy during or after the study. Despite using numerous outcome measures to examine its effect, 25 mg estradiol implants did not produce a greater improvement in the 'urge syndrome' than placebo and had a high complication rate.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Delayed-Action_Preparations_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_pharmacology_MeSH Estradiol_pharmacology_MeSH M_Female_MeSH M_Hemorrhage_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Placebos_MeSH M_Postmenopause_MeSH M_Quality_of_Life_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH M_Urinary_Incontinence_MeSH S_drug_therapy_MeSH Urinary_Incontinence_drug_therapy_MeSH S_etiology_MeSH Urinary_Incontinence_etiology_MeSH M_Vagina_MeSH 
****** 12873780
----K E
----T Local estrogen treatment in patients with urogenital symptoms.
----A OBJECTIVES: Determination of the efficacy and safety of vaginally administered low dose (25 microg) micronized 17beta-estradiol in the management of patients with urogenital symptoms. METHODS: A total of 1612 patients with urogenital complaints were randomized to receive 25 microg of micronized 17beta-estradiol (n=828) or placebo (n=784) in a multicenter double-blind placebo-controlled study running for 12 months. Female patients were treated once a day over a period of 2 weeks, and then twice a week for the remaining of the 12 months with an active or placebo tablet. The assessment included full history-questionnaire, micturition diary, gynecologic and cystometric examination, transvaginal ultrasound, and serum 17beta-estradiol level determination. It was carried out at the beginning, and after 4 and 12 months of treatment. RESULTS: The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5%, and 41.4%, respectively. A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study (51.9% vs. 15.5%, P=0.001). The maximal cystometric capacity (290 ml vs. 200 ml, P=0.023), the volume of the urinary bladder at which patients first felt urgency (180 vs. 140, P=0.048), and strong desire to void (170 ml vs. 130 ml, P=0.045) were significantly increased subsequent to the micronized 17beta-estradiol treatment. The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values (17/30, P=0.013). Side effects were observed in 61 (7.8%) patients treated with low dose micronized 17beta-estradiol. Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth. CONCLUSIONS: Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints.
----P Clinical_Trial Journal_Article Multicenter_Study Randomized_Controlled_Trial 
----M M_Administration__Intravaginal_MeSH M_Atrophy_MeSH M_Double-Blind_Method_MeSH M_Drug_Administration_Schedule_MeSH M_Estradiol_MeSH S_administration_&_dosage_MeSH Estradiol_administration_&_dosage_MeSH S_adverse_effects_MeSH Estradiol_adverse_effects_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Estrogen_Replacement_Therapy_MeSH S_methods_MeSH Estrogen_Replacement_Therapy_methods_MeSH M_Female_MeSH M_Human_MeSH M_Medical_History_Taking_MeSH M_Middle_Aged_MeSH M_Postmenopause_MeSH M_Questionnaires_MeSH M_Treatment_Outcome_MeSH M_Urogenital_System_MeSH S_drug_effects_MeSH Urogenital_System_drug_effects_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Diseases_MeSH S_drug_therapy_MeSH Vaginal_Diseases_drug_therapy_MeSH S_pathology_MeSH Vaginal_Diseases_pathology_MeSH 
****** 13678382
----K E
----T Hormone replacement therapy in postmenopausal women.
----A Hormone replacement therapy (HRT) is effective for relieving vasomotor symptoms such as hot flash and vaginal atrophy and for preventing bone loss in postmenopausal and bilaterally ovariectomized women. However, compliance with HRT was reported to be low despite the benefits of HRT. In addition, results of several recent large-scale randomized clinical trials have demonstrated that protection from cardiovascular disease is not an indication for treatment with estrogen and progestin in postmenopausal women. Recent studies have demonstrated that low-dose HRT is safe and effective for prevention of postmenopausal bone loss. Low-dose HRT has also been shown to be effective for reducing the number and severity of hot flashes, improving vaginal atrophy, and inducing favorable changes in lipids, lipoproteins and hemostatic factors. Moreover, low-dose regimens of CEE (conjugated equine estrogen) and MPA (medroxyprogesterone acetate) result in higher rates of amenorrhea and endometrial protection compared with the conventional dose of HRT. Low-dose HRT may improve the compliance rate and may be more effective than conventional-dose HRT for reducing the risk of breast cancer. On the other hand, it has been shown that transdermal estrogen treatment reduces the incidence and severity of hot flashes and that long-term treatment with transdermally administered estrogen is effective for protection against osteoporosis. Transdermal administration of estrogen is recommended in postmenopausal women with hypertriglycemia because this treatment has little effect on lipid metabolism. The serum estradiol level was reported to be closely related to estrogenic effects on various tissues. An HRT regimen should be based on the needs of each patient. Serum estradiol levels in women should be maintained at appropriate levels for benefits and not be excessively high in order to prevent side effects. Selection of the most appropriate regimen of HRT (dose, route of administration and schedule) for the needs of the individual are important factors to increase the rate of continuation with HRT.
----P Journal_Article Review Review__Tutorial 
----M M_Administration__Cutaneous_MeSH M_Atrophy_MeSH S_drug_therapy_MeSH Atrophy_drug_therapy_MeSH M_Breast_Neoplasms_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH M_Female_MeSH M_Hot_Flashes_MeSH S_drug_therapy_MeSH Hot_Flashes_drug_therapy_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH M_Osteoporosis__Postmenopausal_MeSH S_prevention_&_control_MeSH Osteoporosis__Postmenopausal_prevention_&_control_MeSH P_Postmenopause_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_MeSH M_Vagina_MeSH S_pathology_MeSH Vagina_pathology_MeSH 
****** 14501599
----K E
----T Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women.
----A OBJECTIVE: Circulating testosterone in women declines during the late reproductive years such that otherwise healthy women in their 40s have approximately half the testosterone level as women in their 20s. Despite this, research showing the benefits of androgen replacement has been limited to the postmenopausal years. In view of the known premenopausal physiological decline in testosterone, we have evaluated the efficacy of transdermal testosterone therapy on mood, well-being, and sexual function in eugonadal, premenopausal women presenting with low libido. DESIGN: Premenopausal women with low libido participated in a randomized, placebo-controlled, crossover, efficacy study of testosterone cream (10 mg/day) with two double-blind, 12-week, treatment periods separated by a single-blind, 4-week, washout period. RESULTS: Thirty-four women completed the study per protocol, with 31 women (mean age 39.7 +/- 4.2 years; serum testosterone 1.07 + 0.50 nmol/L) providing complete data. Testosterone therapy resulted in statistically significant improvements in the composite scores of the Psychological General Well-Being Index [+12.9 (95% CI, +4.6 to +21.2), P = 0.003] and the Sabbatsberg Sexual Self-Rating Scale [+15.7 (95% CI, +6.5 to +25.0), P = 0.001] compared with placebo. A mean decrease in the Beck Depression Inventory score approached significance [-2.8 (95% CI, -5.7 to +0.1), P = 0.06]. Mean total testosterone levels during treatment were at the high end of the normal range, and estradiol was unchanged. No adverse effects were reported. CONCLUSIONS: Testosterone therapy improves well-being, mood, and sexual function in premenopausal women with low libido and low testosterone. As a substantial number of women experience diminished sexual interest and well-being during their late reproductive years, further research is warranted to evaluate the benefits and safety of longer-term intervention.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Administration__Cutaneous_MeSH M_Adult_MeSH M_Affect_MeSH S_drug_effects_MeSH Affect_drug_effects_MeSH M_Androgens_MeSH S_blood_MeSH Androgens_blood_MeSH S_therapeutic_use_MeSH Androgens_therapeutic_use_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Female_MeSH M_Human_MeSH M_Libido_MeSH S_drug_effects_MeSH Libido_drug_effects_MeSH M_Ointments_MeSH M_Premenopause_MeSH S_blood_MeSH Premenopause_blood_MeSH S_psychology_MeSH Premenopause_psychology_MeSH M_Psychiatric_Status_Rating_Scales_MeSH M_Sex_Hormone-Binding_Globulin_MeSH S_metabolism_MeSH Sex_Hormone-Binding_Globulin_metabolism_MeSH M_Support__Non-U_S__Gov't_MeSH M_Testosterone_MeSH S_blood_MeSH Testosterone_blood_MeSH S_therapeutic_use_MeSH Testosterone_therapeutic_use_MeSH 
****** 14501603
----K E
----T Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen.
----A OBJECTIVE: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability. DESIGN: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task. RESULTS: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group. CONCLUSION: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Double-Blind_Method_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Memory_MeSH S_drug_effects_MeSH Memory_drug_effects_MeSH M_Middle_Aged_MeSH M_Neuropsychological_Tests_MeSH P_Postmenopause_MeSH P_Reading_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Verbal_Behavior_MeSH S_drug_effects_MeSH Verbal_Behavior_drug_effects_MeSH M_Verbal_Learning_MeSH S_drug_effects_MeSH Verbal_Learning_drug_effects_MeSH M_Vocabulary_MeSH 
****** 14501605
----K E
----T Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial.
----A OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women. We studied the effects of ospemifene on hormone levels, genital tract organs, climacteric symptoms, and quality of life. DESIGN: A double-blinded study in which 160 postmenopausal women were randomly allocated to receive either ospemifene at three different daily doses (30, 60, or 90 mg) or placebo for 3 months. RESULTS: No significant differences were observed among the study groups in clinical characteristics or parameters reflecting estrogen action at baseline. Ospemifene reduced follicle-stimulating hormone and insulin-like growth factor I levels, whereas estradiol failed to change at all, and luteinizing hormone was reduced only in the 90-mg group of ospemifene. In the vast majority of participants, the endometrium remained atrophic after 3 months of treatment with ospemifene. Although the rate of proliferative endometrium slightly increased in all groups, including placebo, no hyperplasia or bleeding occurred in any participant. Ospemifene had no effect on the appearance of proliferation marker Ki-67 in the endometrium as compared with placebo, and endometrial thickness increased by mean 0.4 to 0.6 mm (P < 0.01, P < 0.05 and P < 0.05 for 30, 60 and 90 mg ospemifene, respectively). Uterine volume slightly increased (8.4%-14.7%) in the ospemifene groups (P > 0.05), perhaps as a result of increased uterine blood flow. The most conspicuous finding was the significant estrogenic effect on vaginal epithelium, as evidenced by an increase in intermediate and superficial cells in repeat Pap smears. Ospemifene was not observed to aggravate climacteric symptoms or cause adverse events, nor did it suppress climacteric symptoms. CONCLUSIONS: Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period. Such effects would be advantageous if ospemifene were found to be effective in the long-term prevention of osteoporosis.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Aged_MeSH M_Dose-Response_Relationship__Drug_MeSH M_Double-Blind_Method_MeSH M_Endometrium_MeSH S_drug_effects_MeSH Endometrium_drug_effects_MeSH S_ultrasonography_MeSH Endometrium_ultrasonography_MeSH M_Female_MeSH M_Follicle_Stimulating_Hormone_MeSH S_blood_MeSH Follicle_Stimulating_Hormone_blood_MeSH M_Human_MeSH M_Insulin-Like_Growth_Factor_I_MeSH S_analysis_MeSH Insulin-Like_Growth_Factor_I_analysis_MeSH M_Luteinizing_Hormone_MeSH S_blood_MeSH Luteinizing_Hormone_blood_MeSH M_Middle_Aged_MeSH P_Postmenopause_MeSH P_Quality_of_Life_MeSH M_Selective_Estrogen_Receptor_Modulators_MeSH S_pharmacology_MeSH Selective_Estrogen_Receptor_Modulators_pharmacology_MeSH S_therapeutic_use_MeSH Selective_Estrogen_Receptor_Modulators_therapeutic_use_MeSH M_Support__Non-U_S__Gov't_MeSH M_Tamoxifen_MeSH S_analogs_&_derivatives_MeSH Tamoxifen_analogs_&_derivatives_MeSH S_pharmacology_MeSH Tamoxifen_pharmacology_MeSH S_therapeutic_use_MeSH Tamoxifen_therapeutic_use_MeSH M_Vagina_MeSH S_drug_effects_MeSH Vagina_drug_effects_MeSH S_pathology_MeSH Vagina_pathology_MeSH M_Vaginal_Smears_MeSH 
****** 14592587
----K E
----T Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial.
----A OBJECTIVE: Some postmenopausal women lose genital sexual responsivity despite preserved subjective sexual arousal from non-genital stimuli. When oestrogen replacement is without benefit, both the underlying pathophysiology and management of this acquired genital female sexual arousal disorder are unclear. We aimed to study the effect of sildenafil on sexual arousal and orgasmic functioning of such women. Secondly, we aimed to explore the concordance between a detailed historical assessment of genital response in real life, with laboratory vaginal photoplethysmographic assessment of genital vasocongestion. DESIGN: Session one consisted of a semi-structured clinical interview to assess real life sexual arousal. Session two employed vaginal pulse amplitude and self-report questionnaire assessment of erotica-induced sexual arousal. Sessions three and four were a randomised, double-blind, placebo-controlled crossover administration of sildenafil on orgasm latency, intensity, perception of genital congestion and subjective arousal to erotica plus clitoral vibrostimulation. SETTING: University associated Sexual Medicine Clinic and Psychophysiology Laboratory. SAMPLE: Volunteer sample of 34 oestrogenised postmenopausal women with acquired genital female sexual arousal disorder and impaired orgasm. METHODS: Sildenafil (50 mg) or placebo administered over two laboratory sessions. MAIN OUTCOME MEASURES: Orgasm latency and intensity during drug sessions; subjective and psychophysiological sexual arousal during photoplethysmography session. RESULTS: The erotic video significantly increased subjective sexual arousal in all women. Vaginal pulse amplitude responses varied from robust to absent. Although across all women, sildenafil improved neither arousal nor orgasm, subsequent analyses comparing high versus low vaginal pulse amplitude responders revealed significantly reduced latency to orgasm, and increased subjective sexual arousal and perception of genital arousal in the latter group of women. CONCLUSION: The data suggest that oestrogenised postmenopausal women with genital female sexual arousal disorder and orgasmic impairment based only on clinical assessment do not benefit from sildenafil. However, the photoplethysmograph had predictive value-those women showing low vaginal pulse amplitude response benefited from sildenafil compared with women with a higher response. Thus, oestrogenised women diagnosed with acquired genital female sexual arousal disorder may be a heterogeneous group and the photoplethysmograph might be useful in their further characterisation.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Aged_MeSH M_Analysis_of_Variance_MeSH M_Arousal_MeSH S_drug_effects_MeSH Arousal_drug_effects_MeSH M_Double-Blind_Method_MeSH M_Erotica_MeSH P_Estrogen_Replacement_Therapy_MeSH M_Female_MeSH M_Human_MeSH M_Libido_MeSH M_Middle_Aged_MeSH M_Orgasm_MeSH S_drug_effects_MeSH Orgasm_drug_effects_MeSH M_Phosphodiesterase_Inhibitors_MeSH S_therapeutic_use_MeSH Phosphodiesterase_Inhibitors_therapeutic_use_MeSH M_Piperazines_MeSH S_therapeutic_use_MeSH Piperazines_therapeutic_use_MeSH M_Postmenopause_MeSH M_Pulse_MeSH M_Reaction_Time_MeSH M_Sex_Disorders_MeSH S_drug_therapy_MeSH Sex_Disorders_drug_therapy_MeSH S_physiopathology_MeSH Sex_Disorders_physiopathology_MeSH S_psychology_MeSH Sex_Disorders_psychology_MeSH M_Support__Non-U_S__Gov't_MeSH M_Vagina_MeSH S_blood_supply_MeSH Vagina_blood_supply_MeSH 
****** 14593008
----K E
----T Treatment of postnatal depression.
----A 
----P Editorial 
----M M_Antidepressive_Agents_MeSH S_therapeutic_use_MeSH Antidepressive_Agents_therapeutic_use_MeSH M_Cognitive_Therapy_MeSH S_methods_MeSH Cognitive_Therapy_methods_MeSH M_Combined_Modality_Therapy_MeSH M_Depression__Postpartum_MeSH S_diagnosis_MeSH Depression__Postpartum_diagnosis_MeSH S_therapy_MeSH Depression__Postpartum_therapy_MeSH M_Female_MeSH M_Human_MeSH M_Postnatal_Care_MeSH S_methods_MeSH Postnatal_Care_methods_MeSH M_Psychotherapy_MeSH S_methods_MeSH Psychotherapy_methods_MeSH M_Randomized_Controlled_Trials_MeSH 
****** 14596626
----K E
----T Evaluating minimal clinically important differences for the acne-specific quality of life questionnaire.
----A BACKGROUND: The Acne-Specific Quality of Life Questionnaire (Acne-QoL) is a responsive, reliable and valid instrument developed to measure the impact of facial acne across four dimensions of patient QOL. Score changes on this instrument have been used to report statistically significant treatment advantages for a low-dose oral contraceptive (Estrostep, containing norethisterone (norethindrone) acetate (NA) 1mg and ethinylestradiol (EE) [20, 30, 35 mg] as compared with placebo in women with moderate acne vulgaris. However, the question remained if these statistically significant results were also clinically meaningful. OBJECTIVES: To evaluate the statistically significant Acne-QoL benefits observed with NA/EE in terms of their clinical significance, and to compare the three different approaches for defining a minimal clinically important difference (MCID) for the Acne-QoL instrument. METHODS: Since the optimum method for estimating MCIDs has yet to be established, three different published approaches for determining MCIDs were applied and compared using data from two randomised, double-blind, placebo- controlled studies of the efficacy of NA/EE in the treatment of facial acne. RESULTS: Although the approaches differed substantially, the resulting MCID estimates were comparable. Specifically, the MCID estimates ranged from 0.50-10.3 mean change per item, depending on the domain. The results showed that the statistically significant treatment advantages for NA/EE were also clinically significant. CONCLUSION: When applied to the change scores present, the results showed that the statistically significant treatment advantages for NA/EE were also clinically significant.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Acne_Vulgaris_MeSH S_drug_therapy_MeSH Acne_Vulgaris_drug_therapy_MeSH S_psychology_MeSH Acne_Vulgaris_psychology_MeSH M_Adolescent_MeSH M_Adult_MeSH M_Contraceptives__Oral__Combined_MeSH S_therapeutic_use_MeSH Contraceptives__Oral__Combined_therapeutic_use_MeSH M_Ethinyl_Estradiol_MeSH S_therapeutic_use_MeSH Ethinyl_Estradiol_therapeutic_use_MeSH M_Female_MeSH M_Human_MeSH M_Middle_Aged_MeSH M_Norethindrone_MeSH S_therapeutic_use_MeSH Norethindrone_therapeutic_use_MeSH M_Psychometrics_MeSH M_Quality_of_Life_MeSH S_psychology_MeSH Quality_of_Life_psychology_MeSH M_Questionnaires_MeSH M_Self_Concept_MeSH P_Sickness_Impact_Profile_MeSH M_Support__Non-U_S__Gov't_MeSH M_Treatment_Outcome_MeSH 
****** 14607578
----K E
----T Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial.
----A OBJECTIVE: The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism. DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research center, university hospital. PATIENT(S): Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy. INTERVENTION(S): Collection of serum and urine samples and measurement of bone density.Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks. RESULT(S): In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Adult_MeSH M_Bone_Density_MeSH M_Calcium_MeSH S_blood_MeSH Calcium_blood_MeSH S_metabolism_MeSH Calcium_metabolism_MeSH S_urine_MeSH Calcium_urine_MeSH M_Cross-Over_Studies_MeSH M_Double-Blind_Method_MeSH M_Endometriosis_MeSH S_drug_therapy_MeSH Endometriosis_drug_therapy_MeSH S_metabolism_MeSH Endometriosis_metabolism_MeSH M_Female_MeSH M_Gonadorelin_MeSH S_agonists_MeSH Gonadorelin_agonists_MeSH M_Homeostasis_MeSH M_Human_MeSH M_Leiomyomatosis_MeSH S_drug_therapy_MeSH Leiomyomatosis_drug_therapy_MeSH S_metabolism_MeSH Leiomyomatosis_metabolism_MeSH M_Leuprolide_MeSH S_therapeutic_use_MeSH Leuprolide_therapeutic_use_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_therapeutic_use_MeSH Medroxyprogesterone_17-Acetate_therapeutic_use_MeSH M_Placebos_MeSH M_Support__Non-U_S__Gov't_MeSH M_Support__U_S__Gov't__P_H_S__MeSH M_Uterine_Neoplasms_MeSH S_drug_therapy_MeSH Uterine_Neoplasms_drug_therapy_MeSH S_metabolism_MeSH Uterine_Neoplasms_metabolism_MeSH 
****** 14615509
----K E
----T Estrogen research. Brain researchers try to salvage estrogen treatments.
----A 
----P News 
----M M_Age_Factors_MeSH M_Aged_MeSH M_Animals_MeSH M_Brain_MeSH S_drug_effects_MeSH Brain_drug_effects_MeSH M_Cerebrovascular_Accident_MeSH S_chemically_induced_MeSH Cerebrovascular_Accident_chemically_induced_MeSH S_complications_MeSH Cerebrovascular_Accident_complications_MeSH M_Cognition_MeSH S_drug_effects_MeSH Cognition_drug_effects_MeSH M_Dementia_MeSH S_etiology_MeSH Dementia_etiology_MeSH M_Drug_Combinations_MeSH P_Estrogen_Replacement_Therapy_MeSH S_adverse_effects_MeSH Estrogen_Replacement_Therapy_adverse_effects_MeSH M_Estrogens_MeSH S_pharmacology_MeSH Estrogens_pharmacology_MeSH M_Estrogens__Conjugated_(USP)_MeSH S_administration_&_dosage_MeSH Estrogens__Conjugated_(USP)_administration_&_dosage_MeSH S_adverse_effects_MeSH Estrogens__Conjugated_(USP)_adverse_effects_MeSH S_pharmacology_MeSH Estrogens__Conjugated_(USP)_pharmacology_MeSH M_Female_MeSH M_Human_MeSH M_Medroxyprogesterone_17-Acetate_MeSH S_administration_&_dosage_MeSH Medroxyprogesterone_17-Acetate_administration_&_dosage_MeSH S_adverse_effects_MeSH Medroxyprogesterone_17-Acetate_adverse_effects_MeSH S_pharmacology_MeSH Medroxyprogesterone_17-Acetate_pharmacology_MeSH M_Middle_Aged_MeSH M_Neurons_MeSH S_drug_effects_MeSH Neurons_drug_effects_MeSH S_metabolism_MeSH Neurons_metabolism_MeSH M_Neuroprotective_Agents_MeSH S_pharmacology_MeSH Neuroprotective_Agents_pharmacology_MeSH M_Patient_Selection_MeSH M_Progesterone_MeSH S_pharmacology_MeSH Progesterone_pharmacology_MeSH M_Randomized_Controlled_Trials_MeSH M_Risk_Factors_MeSH M_Time_Factors_MeSH 
****** 14624409
----K E
----T Influence of alpha-adrenergic blockade on the catecholamine response to exercise at 4,300 meters.
----A This investigation examined the influence of alpha-adrenergic blockade on plasma and urinary catecholamine responses to both exercise and high-altitude exposure. Sixteen nonsmoking, eumenorrheic women (age 23.2 +/- 1.4 years, 68.7 +/- 1.0 kg) were studied at sea level and during 12 days of high-altitude exposure (4,300 m). Subjects received either alpha-blockade (prazosin 3 mg/d) or a placebo in a double-blinded, randomized fashion. Resting plasma and 24-hour urine samples were collected periodically throughout the duration of the study. Further, subjects participated in submaximal exercise tests (50 minutes at 50% sea level maximum oxygen consumption [Vo2max]) at Sea level and on days 1 and 12 at altitude. Urinary norepinephrine (NE) excretion rates increased significantly over time at altitude, with blocked subjects having greater values compared to controls. Plasma NE levels increased significantly with chronic altitude exposure compared to sea level and acute hypoxia both at rest and during exercise. NE levels at rest were greater for blocked compared to control subjects during all conditions. Urinary and plasma epinephrine (EPI) levels increased dramatically, with acute altitude exposure returning to sea level values by day 12 of altitude exposure. EPI levels were greater for blocked compared to placebo both at rest and during exercise for all conditions studied. Changes in alpha-adrenergic activity over time at altitude were associated with select metabolic and physiologic adjustments. The presence of alpha-blockade significantly affected these responses during chronic altitude exposure. It was concluded that: (1) alpha-adrenergic blockade elicited a potentiated sympathoadrenal response to the stress of both exercise as well as high-altitude exposure, and (2) the sympathetics, via alpha-adrenergic stimulation, contribute to a number of key adaptations associated with acclimatization to high altitude.
----P Clinical_Trial Journal_Article Randomized_Controlled_Trial 
----M M_Acclimatization_MeSH S_drug_effects_MeSH Acclimatization_drug_effects_MeSH S_physiology_MeSH Acclimatization_physiology_MeSH M_Adrenergic_alpha-Agonists_MeSH S_pharmacology_MeSH Adrenergic_alpha-Agonists_pharmacology_MeSH M_Adrenergic_alpha-Antagonists_MeSH S_pharmacology_MeSH Adrenergic_alpha-Antagonists_pharmacology_MeSH M_Adult_MeSH P_Altitude_MeSH M_Basal_Metabolism_MeSH S_drug_effects_MeSH Basal_Metabolism_drug_effects_MeSH S_physiology_MeSH Basal_Metabolism_physiology_MeSH M_Catecholamines_MeSH S_blood_MeSH Catecholamines_blood_MeSH S_urine_MeSH Catecholamines_urine_MeSH M_Double-Blind_Method_MeSH M_Estradiol_MeSH S_blood_MeSH Estradiol_blood_MeSH M_Exercise_MeSH S_physiology_MeSH Exercise_physiology_MeSH M_Female_MeSH M_Human_MeSH M_Menstrual_Cycle_MeSH S_physiology_MeSH Menstrual_Cycle_physiology_MeSH M_Oxygen_Consumption_MeSH S_drug_effects_MeSH Oxygen_Consumption_drug_effects_MeSH S_physiology_MeSH Oxygen_Consumption_physiology_MeSH M_Phenylephrine_MeSH S_pharmacology_MeSH Phenylephrine_pharmacology_MeSH M_Plasma_Volume_MeSH S_drug_effects_MeSH Plasma_Volume_drug_effects_MeSH S_physiology_MeSH Plasma_Volume_physiology_MeSH M_Prazosin_MeSH S_pharmacology_MeSH Prazosin_pharmacology_MeSH M_Progesterone_MeSH S_blood_MeSH Progesterone_blood_MeSH M_Support__U_S__Gov't__Non-P_H_S__MeSH M_Sympathetic_Nervous_System_MeSH S_drug_effects_MeSH Sympathetic_Nervous_System_drug_effects_MeSH S_physiology_MeSH Sympathetic_Nervous_System_physiology_MeSH