The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women Relationship between serum levels of sex hormones and progression of subclinical atherosclerosis in postmenopausal women. Managing menopause. The endocrine transition around menopause ‐ a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Association of hyperandrogenemia and hyperestrogenemia with type 2 diabetes in Hispanic postmenopausal women. Effectiveness of a low dose testosterone undecanoate to improve sexual function in postmenopausal women Hormone replacement therapy use and menopausal symptoms among women participating in a behavioral lifestyle intervention. Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study Sex hormone changes during weight loss and maintenance in overweight and obese postmenopausal African-American and non-African-American women Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial. Women’s Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy Reduction in proliferation with six months of letrozole in women on hormone replacement therapy Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women SUBCUTANEOUS HORMONE IMPLANTS FOR THE CONTROL OF CLIMACTERIC SYMPTOMS: A Prospective Study The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms. Reproductive hormone exposure timing and ischemic heart disease: Complicated answers to a simple question. Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Association between endogenous plasma hormone concentrations and fracture risk in men and women: the EPIC-Oxford prospective cohort study The effect of transdermal testosterone on mammographic density in postmenopausal women not receiving systemic estrogen therapy. The effects of hormone therapy on pulmonary function tests in postmenopausal women. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial Associations among oral estrogen use, free testosterone concentration, and lean body mass among postmenopausal women. Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women. Relation of BMI and physical activity to sex hormones in postmenopausal women. A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. Bone Mineral Density and Endogenous Hormones and Risk of Breast Cancer in Postmenopausal Women (United States) The association of endogenous sex hormones, adiposity, and insulin resistance with incident diabetes in postmenopausal women. Testosterone aromatization and cognition in women: a randomized, placebo-controlled trial Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being Ovarian volume assessment in relation to histologic findings and sex hormone levels in women with postmenopausal bleeding and thickened endometrium Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries. Serum hormones and the alcohol-breast cancer association in postmenopausal women. Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Percutaneous administration of testosterone gel in postmenopausal women – a pharmacological study Androgens and estrogens in relation to hot flushes during the menopausal transition. A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women. The effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life – experience from the EPHT trial Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial Interrelationship Between Alcohol Intake and Endogenous Sex-Steroid Hormones on Diabetes Risk in Postmenopausal Women Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women. Testosterone for low libido in postmenopausal women not taking estrogen. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.
Menopause impacts 25 million women world wide each year , and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030 . Menopause has been associated with symptoms of hot flashes , night sweats , dysphoric mood , sleep disturbance , and conditions of cardiovascular disease , depression , osteoporosis , osteoarthritis , depression , dementia , and frailty . Conventional hormone replacement therapy results in increased thrombotic events , and an increased risk of breast cancer and dementia as evidence d in large prospect i ve clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women 's Health Initiative . A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors . Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile , yet long-term studies of this treatment model are lacking . The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol , estradiol , progesterone , DHEA , and testosterone on cardiovascular biomarkers , hemostatic , inflammatory , immune signaling factors ; quality -of-life measures ; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care . A prospect i ve , cohort , closed-label study received approval from the Human Subjects Committee . Recruitment from outpatient clinics at an academic medical center and the community at large result ed in three hundred women giving signed consent . Seventy-five women who met strict inclusion /exclusion criteria were enrolled .  Baseline hormone evaluation was performed along with baseline experimental measures . Following this , women received compounded transdermal bioidentical hormone therapy of BiEst ( 80%Estriol/20%Estradiol ) , and /or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women . The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic , ischemic , or neuronal injury . Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of and rogens of DHEA and Testosterone if indicated . Experimental subjects were monitored for 36 months . Baseline , 2-month , and annual values were obtained for : blood pressure , body mass index , fasting glucose , Homeostasis Metabolic Assessment of Insulin Resistance ( HOMA-IR ) , fasting triglycerides , total Factor VII , Factor VIII , fibrinogen , Antithrombin III , Plasminogen Activator Inhibitor1(PAL-1 ) , C-reactive protein ( CRP ) , Interleukin-6 ( IL-6 ) , Matrix Metalloproteinase-9 ( MMP-9 ) , Tumor Necrosis Factor-alpha ( TNF ) , Insulin-like Growth Factor ( IGF-1 ) , and sex steroid levels . Psychosocial measures included : Greene Climacteric Scale , Visual Analog Pain Scale , Hamilton Anxiety Scale , Hamilton Depression Scale , Holmes Rahe Stress Scale , Job Strain , and Home Strain . Health outcome measures included the number of prescribed medications used , number of co-morbidities , and endometrial thickness in postmenopausal women with intact uteri . Subjects receiving  compounded transdermal bioidentical hormone therapy showed significant favorable changes in : Greene Climacteric Scale scores , Hamilton Anxiety Scale , Hamilton Depression Scale , Visual Analog Pain Scale , fasting glucose , fasting triglycerides , MMP-9 , C-reactive Protein , fibrinogen , Factor VII , Factor VIII , Insulin-Like Growth Factor 1 , and health outcomes of co-morbidities and a number of prescribed medications . Antithrombin III levels were significantly decreased at 36 months . All other measures did not exhibit significant effects . Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women . Cardiovascular biomarkers , inflammatory factors , immune signaling factors , and health outcomes were favorably impacted , despite very high life stress , and home and work strain in study subjects . The therapy did not adversely alter the net prothrombotic potential , and there were no associated adverse events . This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in population s with high perceived stress and a history of stressful life events prior to , or during the menopausal transition Background —Despite diffuse effects of sex hormones on the cardiovascular system , few prospect i ve studies have examined the relationship of plasma and rogens and estrogens with risk of cardiovascular disease ( CVD ) in postmenopausal women . Methods and Results —A nested case-control study was performed among women in the Women ’s Health Study . Two hundred women who developed CVD were matched 1:1 by age , smoking , and postmenopausal hormone therapy ( HT ) to controls who remained free of CVD . We measured testosterone , estradiol , and sex hormone binding globulin ( SHBG ) levels and calculated free and rogen index ( FAI ) , free estradiol index , and the FAI/free estradiol index ratio .  Results were stratified by HT use . Among HT nonusers , cases had significantly higher and rogen profiles ( higher median FAI and lower SHBG levels ) than controls . After adjustment for age , smoking , use of aspirin , vitamin E , and alcohol , family history of myocardial infa rct ion , and physical activity , nonusers in the lowest SHBG quartile had an OR of 2.25 ( 95 % CI , 1.03 to 4.91 ) for CVD , and there were significant trends across FAI quartiles ( P for trend=0.03 ) . Additional adjustment for body mass index , hypertension , diabetes , and elevated cholesterol eliminated associations with SHBG and FAI . Among women using HT , no significant differences in hormones or SHBG were observed among women who developed CVD and controls . Conclusions —Among HT nonusers , lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events , but this was not independent of body mass index and other cardiovascular risk factors . Estradiol levels were not associated with risk of CVD in  HT  users or nonusers BACKGROUND Postmenopausal hormone therapy has been examined extensively in relation to cardiovascular disease . However , research relating serum levels of sex hormones to cardiovascular disease is sparse , and the results are inconclusive . METHODS We measured sex hormones in longitudinally collected sample s of 180 postmenopausal women , 91 r and omized to 17beta-estradiol and 89 to placebo , in the Estrogen in the Prevention of Atherosclerosis Trial . Repeated measures of sex hormone levels were tested for an association with carotid artery intima-media thickness ( CIMT ) , which was also assessed longitudinally over 2 yr . RESULTS In all women , changes in serum estrone ( P = 0.02 ) , total estradiol ( P = 0.01 ) , free estradiol ( P = 0.02 ) , and SHBG ( P = 0.005 ) were significantly inversely associated with CIMT progression , controlling for age and body mass index . All the estrogen compounds and SHBG were significantly inversely related with low-density lipoprotein cholesterol and positively associated with high-density lipoprotein cholesterol ( all P < 0.0001 ) , whereas free testosterone was positively related with low-density lipoprotein cholesterol and inversely associated with high-density lipoprotein cholesterol ( P < 0.003 ) . Despite an increase in serum-free estradiol with estradiol therapy , women with unchanged SHBG and free testosterone levels had an average ( se ) progression in CIMT of 8.53 ( 4.72 ) microm/yr , whereas women with increased free estradiol and SHBG and decreased free testosterone had the largest reduction in CIMT progression [ -5.45 ( 2.77 ) microm/yr ; trend P = 0.03 ] . CONCLUSION Estrogen and SHBG are associated with reduced sub clinical atherosclerosis progression in healthy postmenopausal women . These associations are partially mediated by their beneficial effects on lipids . Among women taking estradiol , the most beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free testosterone OBJECTIVE To provide up date d guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor or urogenital symptoms and on considerations related to cardiovascular disease , breast cancer , urogynaecology , and sexuality . OUTCOMES Lifestyle interventions , prescription medications , and complementary and alternative therapies are presented according to their efficacy in the treatment of menopausal symptoms . Counselling and therapeutic strategies for sexuality concerns in the peri- and postmenopausal years are review ed . Approaches to the identification and evaluation of women at high risk of osteoporosis , along with options for prevention and treatment , are presented in the companion osteoporosis guideline . EVIDENCE Published literature was retrieved through search es of PubMed and The Cochrane Library in August and September 2012 with the use of appropriate controlled vocabulary ( e.g. , hormone therapy , menopause , cardiovascular diseases , and sexual function ) and key words ( e.g. , hormone therapy , perimenopause , heart disease , and sexuality ) . Results were restricted to clinical practice guidelines , systematic review s , r and omized control trials/controlled clinical trials , and observational studies . Results were limited to publication date s of 2009 onwards and to material in English or French . Search es were up date d on a regular basis and incorporated in the guideline until January 5 , 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology assessment -related agencies , national and international medical specialty societies , and clinical practice guideline collection OBJECTIVE The purpose of this study was to investigate the hormonal changes during the menopausal transition in a non- clinical population . METHODS Fifty-nine healthy Norwegian women participated in a five year prospect i ve longitudinal study during the transition from pre- to post-menopause , starting one to four years before menopause , and ending one to four years postmenopausal . None of these women were given hormone replacement therapy ( HRT ) . Blood sample s were collected every 12 months and luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , steroid hormone binding globuline ( SHBG ) , prolactin ( PRL ) , estradiol ( E2 ) , estrone ( E1 ) , testosterone , and rostendione , dehydroepi and rostendione-sulphate ( DHEA-S ) , and thyroid stimulating hormone ( TSH ) were analyzed . RESULTS The serum levels of FSH and LH , E2 and E1 profile essentially confirmed previous data obtained in cross-sectional studies . A continuous increase in serum FSH and LH and a concomitant fall in E2 and E1 were observed in all women before menopause and in the two postmenopausal years . Both and rostendione and testosterone showed a decline three years before menopause . After the menopause , however , there were fluctuations in the testosterone levels . And rostendione correlated positively with both E2 and E1 and testosterone postmenopausally . Body mass index ( BMI ) did correlate with testosterone , but not with and rostendione . BMI correlated negatively with SHBG . No correlation was found between BMI and E2 , E1 , FSH and LH . CONCLUSION This longitudinal prospect i ve study of hormonal changes during the transition from pre- to postmenopause indicates that not only estrogen hormonal changes , but and rogen hormonal changes as well , precedes the menopause by several years Objective . To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women . Methods . Fifty surgically postmenopausal women were included in this double-blind , placebo-controlled and r and omized study to receive daily oral treatment with estradiol valerate 2 mg + placebo ( E/P ) or estradiol valerate 2 mg + testosterone undecanoate 40 mg ( E/T ) for 24 weeks and then switched to the other regimen for another 24 weeks . Sex hormones , High sensitivity CRP ( hsCRP ) , Interleukin-6 ( IL-6 ) , Tissue necrosis factor (TNF)-α , Insulin-like growth factor binding globulin ( IGFBP-1 ) , vascular cell adhesion molecule (VCAM)- 1 , and homocysteine were analyzed at baseline and after 6 and 12 months . Results . Estradiol and and rogens increased as expected during the treatments . After 6 months of E/P , increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded , whereas IL-6 , TNF-α , and homocysteine were unchanged . When testosterone was added to estrogen , the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone . However , testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6 , TNF-α , and homocysteine . Conclusion . Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects . On the contrary , the estrogen-induced increase in hsCRP was suppressed High serum levels of testosterone and estradiol , the bioavailability of which may be increased by Western dietary habits , seem to be important risk factors for postmenopausal breast cancer . We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods , monounsaturated and n-3 polyunsaturated fatty acids , and phytoestrogens , might favorably modify the hormonal profile of postmenopausal women . One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were r and omized to dietary intervention or control .  The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months . Changes in serum levels of testosterone , estradiol , and sex hormone-binding globulin were the main outcome measures . In the intervention group , sex hormone-binding globulin increased significantly ( from 36.0 to 45.1 nmol/liter ) compared with the control group ( 25 versus 4 % , ; P < 0.0001 ) and serum testosterone decreased ( from 0.41 to 0.33 ng/ml ; -20 versus -7 % in control group ; P = 0.0038 ) . Serum estradiol also decreased , but the change was not significant . The dietary intervention group also significantly decreased body weight ( 4.06 kg versus 0.54 kg in the control group ) , waist : hip ratio , total cholesterol , fasting glucose level , and area under insulin curve after oral glucose tolerance test . A radical modification in diet design ed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyper and rogenic postmenopausal women . Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer OBJECTIVE Accumulating evidence suggests that hyper and rogenemia may be a risk factor for coronary heart disease ( CHD ) in women . The present study was carried out to test the hypothesis that hyper and rogenemia is associated with type 2 diabetes in women and thus may contribute to the increased risk of CHD in women with type 2 diabetes . RESEARCH DESIGN AND METHODS Sex hormones , sex hormone-binding globulin ( SHBG ) , and  risk factors for CHD were measured in 20 postmenopausal women with type 2 diabetes and in 29 control subjects . All of the diabetic and control subjects were Hispanic women aged > 55 years who were not taking hormone replacement therapy lipid-lowering drugs , or insulin and who were otherwise r and omly chosen from a cohort of stroke-free subjects from the Northern Manhattan Stroke Study RESULTS Mean age , BMI , total cholesterol , LDL cholesterol , HDL cholesterol , triglycerides , blood pressure , and smoking were not significantly different between cases and control subjects , but waist-to-hip ratio ( WHR ) was significantly higher in the diabetic subjects ( P = 0.01 ) . The mean levels of free testosterone ( FT ) ( P = 0.01 ) , dehydroepi and rosterone sulfate ( P<0.04 ) , and estradiol ( P = 0.01 ) ( controlled for WHR ) were significantly higher in the diabetic subjects ; with the statistical outliers removed , the testosterone ( P = 0.05 ) and and rostenedione ( P = 0.002 ) levels ( controlled for WHR ) were also significantly higher in the diabetic subjects . The mean levels of estrone , cortisol , and SHBG were not significantly different . The results were similar in the 10 diabetic subjects treated with diet only Significant positive correlations ( controlled for age and BMI ) were observed between FT or testosterone and cholesterol , LDL cholesterol , and blood pressure . CONCLUSIONS Postmenopausal Hispanic women with type 2 diabetes had both hyper and rogenemia and hyperestrogenemia , and testosterone or FT correlated positively with risk factors for CHD . Hyper and rogenemia may be a link between diabetes and CHD in women Background Adding testosterone to hormonal therapy could improve sexual function and general well-being among women during climacteric . We evaluated the effectiveness of testosterone undecanoate on sexual function in postmenopausal women utilizing the st and ardized question naire FSFI score . Methods Postmenopausal women with sexual complaints and Female Sexual Function Index ( FSFI ) ≤ 26.5 were enrolled in to this r and omized , double-blinded , placebo-controlled trial . Participants were r and omly assigned to 8-week treatment with either oral testosterone undecanoate 40 mg or placebo twice weekly with daily oral estrogen .  The FSFI scores before and after treatment were compared to assess any improvement of sexual function . Results Seventy women were recruited of which each group had 35 participants . The baseline characteristics and baseline FSFI scores were comparable between both groups . After 8 weeks of treatment , the FSFI scores significantly improved in both groups when compared to the baseline but the FSFI scores from the testosterone group were significantly higher than in the placebo group post-treatment ( 28.6 ± 3.6 , 25.3 ± 6.7 , respectively , p = 0.04 ) . There was no difference in adverse effect between the two groups Conclusions The twice weekly addition of testosterone undecanoate to daily oral estrogen was associated with a significant improvement in sexual function  among postmenopausal women than the use of the estrogen alone . Trial registration Clinical Trials.gov Identifier NCT01724658 ( February 17 , 2012 ) BACKGROUND The decision to take hormone replacement therapy ( HRT ) is a choice many women encounter when entering menopause . The purpose of this study was to examine the choice to take HRT while participating in a lifestyle intervention to reduce cardiovascular risk through the menopause . METHODS The Women 's Healthy Lifestyle Project is a r and omized clinical trial design ed to examine whether a behavioral lifestyle intervention can decrease the expected rise in cardiovascular risk through the menopause . Participants ( N = 535 ) completed question naires and were interviewed regarding menopausal symptoms , menopausal status , hot flashes , and  HRT  use at baseline and 54 months . RESULTS The intervention was successful in preventing risk elevation through the 54-month visit . At the final visit , there was no difference between the intervention and control groups in the percentage who had become postmenopausal ( 32.9 % vs 35.0 % , respectively ) , there was no difference between control and intervention with  HRT  use , with 31.2 % reporting use of HRT , and there was no difference between groups with menopausal symptoms . The women started HRT an average of 6 months after they missed a period . Baseline risk factors did not predict HRT use at the 54-month visit . CONCLUSIONS A sizable number of women reported HRT use . The decision to use HRT was not influenced by the lifestyle intervention or their baseline cardiovascular risk , and these women started HRT very early in the peri- to postmenopause . Further , weight loss in the perimenopause did not affect menopausal symptoms In postmenopausal women , levels of estrogens , and rogens , and perhaps prolactin have been related to risk of breast and other hormonal cancers in women . However , the determinants of these hormone concentrations have not been firmly established . Associations among various demographic , menstrual , and reproductive factors , medication use and endogenous sex hormone concentrations ( estradiol , free estradiol , estrone , estrone sulfate , testosterone , free testosterone , sex hormone binding globulin , and rostenedione , dehydroepi and rosterone ( DHEA ) , DHEA sulfate ( DHEAS ) , dihydrotestosterone , and prolactin )  were evaluated in a cross-sectional analysis from a simple r and om sample of 274 postmenopausal women selected from the Women ’s Health Initiative Dietary Modification Trial . In multiple regression analyses on log-transformed hormones , the concentrations of DHEA , and DHEAS were negatively and statistically significantly associated with age ( both β = −0.03 , P < 0.001 , respectively ) . Estradiol , estrone , DHEA , and free testosterone concentrations were higher in African-American than in non-Hispanic White women , but after multivariate adjustment the associations were statistically significant only for free testosterone ( β = 0.38 , P = 0.01 ) . Women who had a history of bilateral oophorectomy had a mean 35 % lower testosterone concentration compared with women with at least one ovary remaining ( β = −0.43 , P = 0.002 ) , and lower free testosterone ( β = −0.42 , P = 0.04 ) after multivariate adjustment . Women who reported regular use of NSAIDs had higher DHEA concentrations ( β = 0.20 , P = 0.04 ) and lower prolactin concentrations ( β = −0.18 , P = 0.02 ) compared with non-users . These results suggest that while age , oophorectomy status , and NSAID use may be associated with selected sex hormone concentrations , few menstrual or reproductive factors affect endogenous sex hormones in the postmenopausal period OBJECTIVE RIA-based sex hormone measurements offer only limited precision and specificity in the low concentration range of women . Therefore , we aim ed to establish age-specific reference ranges for serum sex hormone concentrations in women using mass spectrometry and quantile regression . METHODS AND RESULTS Data from 985 women aged 20 - 80 yr , recruited for the prospect i ve Study of Health in Pomerania , were included in the analyses . Quantile regressions models were performed to calculate the age-specific 2.5th and 97.5th percentiles for sex hormone concentrations in women . Serum total testosterone ( TT ) and and rostenedione ( AD ) concentrations were measured by liquid chromatography-t and em mass spectrometry . Measured concentrations of SHBG and TT were used to calculate free testosterone ( free T ) . TT , AD , and free T concentrations showed a distinct age-related decline across 10-yr age groups ( one way ANOVA P < 0.001 ) . Sex hormone reference ranges for TT , AD , and free T were determined across each single year of age and for 10-yr age groups . Reference ranges over the whole age range of 20 - 80 yr were 0.35 - 1.97 nmol/liter for TT , 0.89 - 4.56 nmol/liter for AD , and 0.0025 - 0.0253 nmol/liter for free T. Separate reference ranges were provided for pre- and postmenopausal women as well as after inclusion of women using oral contraceptives or hormone therapy ( n = 1357 ) . CONCLUSION This is the first study to establish age-specific reference ranges for liquid chromatography-t and em mass spectrometry-measured  TT and AD and calculated free T concentrations based on quantile regression analyses , accurately accounting for the observed low concentration range and the strong age dependency of these sex hormones in women Summary . Forty postmenopausal women , referred for hormone replacement therapy and all of whom reported a significant concern about a decline in their sexual interest , were r and omly allocated to one of two hormone implant  treatment groups : either oestradiol ( 50 mg ) alone , or oestradiol ( 50 mg ) and testosterone ( l00 mg ) . Comparison between the two groups as a whole revealed no significant differences on any measure , both treatments being associated with a significant reduction in the severity of psychological , somatic and vasomotor symptoms , and with a significant improvement in sexual interest and responsiveness . Similar effects were also observed in patients who denied , pretreatment , any concurrent dyspareunia .  Although it is not possible to identify the reasons for change , the results indicate no advantages of supplementary testosterone administration over oestradiol alone for sexually unresponsive postmenopausal women Introduction Changes in sex hormones with weight loss might have implication s for breast cancer prevention but have not been examined extensively , particularly in African-American ( AA ) women . Methods We conducted a prospect i ve study of 278 overweight/obese postmenopausal women ( 38 % AA ) not taking hormone therapy within the Weight Loss Maintenance Trial . All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months . We evaluated the percentage changes in estrone , estradiol , free estradiol , testosterone , free testosterone , and rostenedione , dehydroepi and rosterone sulfate and sex hormone-binding globulin ( SHBG ) using generalized estimating equations . Results In all study phases , AA women had higher levels of estrogen and testosterone concentrations , independent of adiposity . On average , participants lost 7.7 kg during the weight-loss phase , and concentrations of estrone ( -5.7 % , P = 0.006 ) , estradiol ( -9.9 % , P < 0.001 ) , free estradiol ( -13.4 % , P < 0.0001 ) , and free testosterone ( -9.9 % , P < 0.0001 ) decreased , while the SHBG concentration ( 16.2 % , P < 0.001 ) increased . Weight change did not significantly affect total testosterone or other and rogen concentrations . Compared with non-AA women , AA women experienced less change in estrogens per kilogram of weight change ( that is , per 1 kg weight loss : estrone , -0.6 % vs. -1.2 % , P-interaction = 0.10 ; estradiol , -1.1 % vs. -1.9 % , P-interaction = 0.04 ; SHBG , 0.9 % vs. 1.6 % , P-interaction = 0.006 ; free estradiol , -1.4 % vs. -2.1 % , P-interaction = 0.01 ) . Conclusion To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women . Although speculative , these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to underst and the long-term effects of weight loss on sex hormones in obese postmenopausal women . Trial Registration Clinical Trials.gov : Aims /hypothesis Prospect i ve data directly investigating the role of endogenous sex hormones in diabetes risk have been scant , particularly in women . We aim ed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes  in postmenopausal women . Methods We conducted a prospect i ve , nested case – control study of  plasma oestradiol , testosterone and dehydroepi and rosterone sulfate  and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause . Among women not using hormone therapy and free of baseline cardiovascular disease , cancer and diabetes , 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years . Results Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes . After adjustment for BMI , family history , lifestyle and reproductive variables , the multivariable relative risks ( 95 % CI ) comparing the highest vs lowest quintile were 12.6 ( 2.83–56.3 ) for total oestradiol ( p = 0.002 for trend ) , 13.1 ( 4.18–40.8 ) for free oestradiol ( p < 0.001 for trend ) , 4.15 ( 1.21–14.2 ) for total testosterone ( p = 0.019 for trend ) and 14.8 ( 4.44–49.2 ) for free testosterone ( p < 0.001 for trend ) . These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA1c levels . Conclusions /interpretationIn postmenopausal women , higher plasma levels of oestradiol and testosterone were strongly and prospect ively related to increased risk of developing type 2 diabetes . These prospect i ve data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes . Clinical Trials.gov ID no. : NCT00000479 Most studies of sex hormones and insulin resistance ( IR ) have focused on and rogens ; few have examined the association of endogenous estrogens and IR . We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy , postmenopausal women aged 45 - 65 yr . Women were within 10 yr of menopause and not using hormone replacement therapy .  Total adiposity was estimated by body mass index , visceral adiposity by waist to hip ratio ( WHR ) , and IR by the homeostasis model assessment . We defined homeostasis model assessment -IR as the highest quartile ( cutpoint , 2.1 ) of the distribution in this cohort . In logistic regression analyses , the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol , bioavailable estradiol , and bioavailable testosterone ( all P < 0.001 for linear trend ) . These associations remained significant after adjusting for WHR ; adjusted odds ratios were 4.0 , 6.1 , and 2.7 for total estradiol , bioavailable estradiol , and bioavailable testosterone , respectively , comparing the highest to the lowest quartile ( all P < 0.001 ) . Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone , but the association with bioavailable estradiol remained ( adjusted odds ratio , 2.7 ; P < 0.001 , comparing the highest to the lowest quartile ) . IR was not associated with total testosterone before or after adjusting for adiposity . Lower SHBG levels were associated with higher odds of IR , independent of adiposity . These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy , young postmenopausal women , with differences not entirely explained by body size Objective This study aims to test the added value of calcium and vitamin D ( CaD ) in fracture prevention among women taking postmenopausal hormone therapy ( HT ) . Methods This is a prospect i ve , partial-factorial , r and omized , controlled , double-blind trial among Women ’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years . A total of 27,347 women were r and omized to HT ( 0.625 mg of conjugated estrogens alone , or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily ) , and 36,282 women were r and omized to 1,000 mg of elemental calcium ( carbonate ) plus 400 IU of vitamin D3 daily , each compared with placebo .  A total of 16,089 women participated in both arms . The predefined outcomes were adjudicated hip fractures and measured bone mineral density . Results Interaction between HT and CaD on hip fracture ( P interaction = 0.01 ) was shown . The effect of CaD  was stronger among women assigned to HT ( hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.38 - 0.93 ) than among women assigned to placebo ( HR , 1.20 ; 95 % CI , 0.85 - 1.69 ) . The effect of HT on hip fracture was stronger among women assigned to active CaD ( HR , 0.43 ; 95 % CI , 0.28 - 0.66 ) than among women assigned to placebo ( HR , 0.87 ; 95 % CI , 0.60 - 1.26 ) . CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake . There was no interaction between HT and  CaD  on change in hip or spine bone mineral density .  Conclusions Postmenopausal women at normal risk for hip fracture who are on CaD supplementation  experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake The objective of this study was to determine if 6 months of the aromatase inhibitor letrozole , administered to postmenopausal women taking a stable dose of hormone replacement remedy , would be safe and would modulate biomarkers of breast cancer risk . The intent was to reduce the proliferation marker Ki-67 while maintaining adequate systemic levels of estradiol so as to avoid perimenopausal symptoms . Postmenopausal women at high risk for development of breast cancer and taking a stable dose of estrogen or estrogen plus progestin were screened by r and om periareolar fine needle aspiration ( RPFNA ) . To be eligible , the acquired breast epithelial cells had to be characterized as cytologic atypia or borderline atypia with ≥1,000 epithelial cells on the cytomorphology slide ; plus ≥500 epithelial cells on a slide processed for Ki-67 immunocytochemistry . Forty-two women were enrolled in the one arm study and received 2.5 mg letrozole per day for 6 months , followed by repeat assessment of biomarkers . Ki-67 was reduced by a median relative value of 66 % . There was no significant change in breast cell cytomorphology ; ER weighted index score ; serum estradiol , testosterone , or IGF-1:IGFBP-3 ratio ; mammographic breast density , or frequency or severity of perimenopausal symptoms . Given the dramatic reduction in proliferation , the effect of letrozole on risk and response biomarkers should be explored further in a r and omized , placebo-controlled Phase IIB breast cancer chemoprevention trial Objective : During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy , in particular about its effects on the breast . Several observations suggest that and rogens may counteract the proliferative effects of estrogen and progestogen in the mammary gl and . Thus , we aim ed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy . Design : We conducted a 6-month prospect i ve , r and omized , double-blind , placebo-controlled study . A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally r and omly assigned to receive additional treatment with either a testosterone patch releasing 300 & mgr;g/24 hours or a placebo patch . Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months , and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody . Results : A total of 88 women , 47 receiving active treatment and 41 in the placebo group , completed the study . In the placebo group there was a more than fivefold increase ( P < 0.001 ) in total breast cell proliferation from baseline ( median 1.1 % ) to 6 months ( median 6.2 % ) . During testosterone addition , no significant increase was recorded ( 1.6 % vs 2.0 % ) . The different effects of the two treatments were apparent in both epithelial and stromal cells . Conclusions : Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women 55 postmenopausal women on established hormone replacement therapy were treated with either oestradiol and testosterone implants or placebo at the time of return of climacteric symptoms . Their response to therapy was assessed prospect ively . The statistically highly significant levels of symptom relief that followed an oestradiol and testosterone implant were contrasted sharply with the lack of any significant relief with placebo . Despite the success of oestradiol and testosterone implants in relieving symptoms of the climacteric , symptoms returned once the treatment was stopped . Evidence is presented that it is the fall in hormone levels rather than the level itself that provokes the return of climacteric symptoms OBJECTIVE To evaluate the benefits and risks of hormone replacement therapy ( HRT ) combined with methyltestosterone ( MT ) in postmenopausal women with sexual dysfunction .  DESIGN This study was a r and omized , double-blind , placebo-controlled and crossover trial . Eighty-five women using HRT  were divided into four treatment groups : GI-HRT plus placebo for 4 months ; GII-HRT plus MT 2.5mg/day for 4 months ; GIII-HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5mg/day for 2 months ; GIV-HRT plus MT 2.5mg/day and then replaced with HRT plus placebo for 2 months . Blood was collected at baseline , after 2 months ( T1 ) and 4 months ( T2 ) of treatment for hormone determinations of estradiol , FSH , total and free testosterone , GOT , GPT , glucose , total and fractions of cholesterol and triglycerides . All participants answered clinical questions and a vali date d question naire of modified McCoy 's sex scale . RESULTS The association of HRT with MT 2.5mg/day did not significantly change liver enzymes or increase cardiovascular risk factors . The patients of GII , GIIII and GIV when using MT presented amelioration of sex symptoms , mainly satisfaction and desire ( p<0.01 ) ; however , GIII at T1 ( 1.3+/-0.3 ) presented similar problem score results as compared to GIII at T2 ( 1.5+/-0.6 ) . CONCLUSION All data suggest that combined HRT- and rogen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy Premenopausal women have a relatively lower risk of ischemic heart disease ( IHD )  compared to age matched men and this gender gap narrows after menopause . The observation that the onset of IHD occurs 10 years later in women than it does in men is said to suggest that endogenous reproductive hormones play a protective role . Indeed , animal models and human epidemiological studies suggest that oophorectomy is a risk factor for accelerated IHD . In animal models , hormone therapy ( HT ) has anti-atherosclerotic effects after oophorectomy , HT in the form of oral contraceptives ( OCs ) prevents atherosclerosis in anovulatory cycling women , and large numbers of premenopausal women taking OCs have relative safety from an IHD st and point ( 1 ) . Further , observational epidemiological studies in humans have consistently demonstrated protective effects for IHD among HT users . Such studies are typically performed on relatively younger women where  HT  is prescribed for  vasomotor symptoms during menopausal transition or shortly following menopause . In contrast , clinical trials in older , postmenopausal and often asymptomatic women have demonstrated no overall benefit and early adverse effects when r and omized to a variety of forms of HT ( 1 ) . These data discrepancies have called into question the validity of the reproductive hormone estrogen protection hypothesis , and raise the alternative possibility that  HT efficacy may differ according to the timing of exposure . Stated as a simple question , is the effect of HT on the risk of IHD in relatively young pre- or early menopausal women with vasomotor symptoms , different than it is in older , fully menopausal women ? Data from the Women ’s Ischemia Syndrome Evaluation ( WISE ) , a prospect i ve multi-center NHLBI-sponsored study design ed to explore female-specific pathophysiology in a large sample of women undergoing coronary angiography for suspected IHD ( 2 ) , may shed light on this controversy . These new data , prospect ively obtained using novel methods , including detailed reproductive health question naires , menopausal adjudication algorithms , and quantitative coronary angiography as a measure of atherosclerosis , allow a more precise inspection of this question . However , to answer this simple question we need to first answer others . Specifically , how can we integrate and underst and the findings from the available observational , animal and clinical trial data ? And to interpret these data other questions become relevant : 1 ) How accurately was menopause assessed in prior observational HT studies ? 2 ) Does HT in premenopausal women in the form of OC therapy confirm atherosclerosis benefit ? and 3 ) Does HT in early menopausal women confer reduced atherosclerosis and benefit on the risk of IHD The objective of this study was to examine the effects of estrogen-based hormone therapy ( HT ) on regional cerebral metabolism in postmenopausal women ( mean age = 58 , SD = 5 ) at risk for development of dementia . The prospect i ve clinical trial design included pre- and post-intervention neuroimaging of women r and omized to continue ( HT+ ) or discontinue ( HT− ) therapy following an average of 10 years of use . The primary outcome measure was change in brain metabolism during the subsequent two years , as assessed with  fluorodeoxyglucose-18 positron emission tomography ( FDG-PET ) . Longitudinal FDG-PET data were available for 45 study completers . Results showed that women r and omized to continue HT experienced relative preservation of frontal and parietal cortical metabolism , compared with women r and omized to discontinue HT . Women who discontinued 17-β estradiol (17βE)-based HT , as well as women who continued conjugated equine estrogen (CEE)-based HT , exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical ( PCC ) area . Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins ( with either 17βE or CEE ) . Together , these findings suggest that among postmenopausal subjects at risk for developing dementia , regional cerebral cortical metabolism is relatively preserved for at least two years in women r and omized to continue HT , compared with women r and omized to discontinue HT . In addition , continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC , known to undergo the most significant decline in the earliest stages of Alzheimer 's disease . Trial Registration Clinical Trials.gov BACKGROUND Apparently discrepant findings have been reported by the Women 's Health Initiative ( WHI ) trial compared with observational studies of postmenopausal hormone therapy ( HT ) and coronary heart disease ( CHD ) . METHODS We prospect ively examined the relation of HT to CHD , according to timing of hormone initiation relative to age and time since menopause . Participants were postmenopausal women in the Nurses ' Health Study , with follow-up from 1976 to 2000 . Information on hormone use was ascertained in biennial , mailed question naires . We used proportional hazards models to calculate multivariable adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) . We also conducted sensitivity analyses to determine the possible influence of incomplete capture of coronary events occurring shortly after initiation of HT . RESULTS Women beginning HT near menopause had a significantly reduced risk of CHD ( RR = 0.66 , 95 % CI 0.54 - 0.80 for estrogen alone ; RR = 0.72 , 95 % CI 0.56 - 0.92 for estrogen with progestin ) . In the subgroup of women demographically similar to those in the WHI , we found no significant relation between HT and CHD among women who initiated therapy at least 10 years after menopause ( RR = 0.87 , 95 % CI 0.69 - 1.10 for estrogen alone ; RR = 0.90 , 95 % CI 0.62 - 1.29 for estrogen with progestin ) . Among women who began taking hormones at older ages , we also found no relation between current use of estrogen alone and CHD ( for women aged 60 + years , RR = 1.07 , 95 % CI 0.65 - 1.78 ) , although there was a suggestion of possible reduced risk for combined HT ( RR = 0.65 , 95 % CI 0.31 - 1.38 ) . In sensitivity analyses , we found that the incomplete capture of coronary events occurring shortly after initiation of HT could not explain our observation of a reduced risk of coronary disease for current users of HT . CONCLUSIONS These data support the possibility that timing of HT initiation in relation to menopause onset or to age might influence coronary risk OBJECTIVE In some women , a decline in sexual interest accompanies a relative and rogen insufficiency after menopause . We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire . DESIGN Double-blind r and omized trial . SETTING Healthy volunteers in a multicenter research environment . PATIENT(S ) Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire . INTERVENTION(S ) 4 months of treatment with 0.625 mg of esterified estrogens ( n = 111 ) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone ( n = 107 ) . MAIN OUTCOME MEASURES Baseline and end-of- study measurements of total and bioavailable testosterone and sex hormone-binding globulin ( SHBG ) , and mean change in level of sexual interest or desire as rated on the Sexual Interest Question naire . RESULT ( S ) Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG . Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone . Treatment with the combination was well tolerated . CONCLUSION ( S ) Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone OBJECTIVE Use of estrogen-based hormone therapy ( HT ) as a protection from cognitive decline and Alzheimer disease ( AD ) is controversial , although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations . Little is known regarding specific population s of women who may derive benefit from HT . METHODS Women with heightened risk for AD ( aged 49 - 69 ) , all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset , underwent  cognitive assessment  followed by r and omization to continue or discontinue HT . Assessment s were repeated at 2 years after r and omization . RESULTS Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention , working memory , and processing speed measures . Women who used 17β-estradiol versus conjugated equine estrogen , whether r and omized to continue or discontinue HT , showed better verbal memory performance at the 2-year follow-up assessment . An interaction was also found with HT r and omization and family history of AD in a first-degree relative . All female offspring of patients with AD declined in verbal memory ; however , women who continued HT declined less than women who discontinued HT . Women without a first-degree relative with AD showed verbal memory improvement ( likely because of practice effects ) with continuance and declined with discontinuance of HT . CONCLUSION Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset Postmenopausal women with elevated circulating and rogen concentrations have an increased risk of developing breast cancer , yet interventions to reduce and rogen levels have not been identified . We examined the effects of a 12-month moderate intensity exercise intervention on serum and rogens . The study was a r and omized clinical trial in 173 sedentary , overweight ( body mass index > or = 24.0 kg/m(2 ) , body fat > 33 % ) , postmenopausal women , ages 50 to 75 years , not using hormone therapy and living in the Seattle , WA area . The exercise intervention included facility-based and home-based exercise ( 45 minutes , 5 days per week of moderate intensity sports/recreational exercise ) . A total of 170 ( 98.3 % ) women completed the study , with exercisers averaging 171 minutes per week of exercise . Women in the exercise and control groups experienced similar , nonsignificant declines in most and rogens . Among women who lost > 2 % body fat , testosterone and free testosterone concentrations fell by 10.1 % and 12.2 % between baseline and 12 months in exercisers compared with a decrease of 1.6 % and 8.0 % in controls ( P = 0.02 and 0.03 compared with exercisers , respectively ) . Concentrations of testosterone and free testosterone among exercisers who lost between 0.5 % and 2 % body fat declined by 4.7 % and 10.4 % . In controls who lost this amount of body fat , concentrations of testosterone and free testosterone declined by only 2.8 % and 4.3 % ( P = 0.03 and 0.01 compared with exercisers , respectively ) . In summary , given similar levels of body fat loss , women r and omized to a 12-month exercise intervention had greater declines in testosterone and free testosterone compared with controls . The association between exercise and breast cancer risk may be partly explained by the effects of exercise on these hormones Sex steroids have an important role in bone health , however previous studies on fracture risk have been carried out in older population s. The EPIC-Oxford study is a prospect i ve cohort of men and women living in the UK . Five years after recruitment , participants self-reported previous fractures .  Sex steroid concentrations ( plasma estradiol , testosterone and sex hormone binding globulin )  were measured in 436 cases ( 155 men , 46 premenopausal women and 235 postmenopausal women ) with an incident fracture and 868 matched controls .  Fracture risk was inversely related to concentrations of estradiol among men ( RR for a doubling of estradiol 0.35 , 95 % CI 0.44–0.96 ) but there was no association between fracture risk and testosterone levels . There were no clear associations between fracture risk and hormone levels among postmenopausal women , however there was suggestion of an inverse association for both estradiol and testosterone as the RR in the highest compared with the lowest tertile for estradiol was 0.74 ( 95 % CI 0.46 , 1.18 ) and testosterone was 0.75 ( 95 % CI 0.49 , 1.16 ) . Among premenopausal women fracture risk was inversely associated with levels of testosterone ( RR for doubling of testosterone 0.46 , 95 % CI 0.26–0.81 ) , with no association between estradiol and fracture risk . SHBG was not associated with risk of fracture among either men or women . In summary , this study finds evidence of an inverse association between endogenous estradiol and risk of fracture in men , and between endogenous testosterone and risk of fracture in premenopausal women but no clear associations among postmenopausal women CONTEXT Greater mammographic density is associated with increased breast cancer risk and reduced diagnostic mammographic sensitivity and may be seen with estrogen/progestin therapy ( EPT ) . The effects of testosterone therapy on mammographic density in postmenopausal women not on EPT are not known . OBJECTIVE Our objective was to compare effects of two doses of the testosterone transdermal patch ( TTP ) with placebo in postmenopausal women without concomitant EPT on mammographic density  over 52 wk . DESIGN We conducted a r and omized , double-blind , placebo-controlled , parallel-group , multinational trial . PATIENTS Patients included 279 postmenopausal women participating in a testosterone and sexual function study with paired mammograms for baseline and 52 wk/exit . INTERVENTIONS Patients were r and omized to placebo , TTP 150 microg/d , or TTP 300 microg/d , stratified by menopause type ( natural or surgical ) . MAIN OUTCOME MEASURES Change from baseline to wk 52 in the percentage of dense tissue ( PD ) on digital mammograms . RESULTS A total of 250 women with paired mammograms for study baseline and wk 52 were included in the primary analysis . Mean age was 54.6 yr , baseline body mass index was 27.5 kg/m(2 ) , and 78 % were naturally menopausal . There were no baseline differences between groups . Mean changes from baseline ( + /-SEM ) in PD for placebo , TTP 150 microg/d and TTP 300 microg/d were small ( 0.05 + /- 0.16 , 0.06 + /- 0.19 , and 0.21 + /- 0.17 % ) and not significantly different . There were no statistically significant differences from placebo for total dense or nondense area and no significant relationships between hormone levels and PD after adjustment for body mass index . CONCLUSION TTP therapy over 52 wk appears to have no significant effect on digitally quantified absolute or percent dense mammographic area in postmenopausal women not using EPT OBJECTIVE To investigate the effects of hormone therapy ( HT ) administered to postmenopausal women on pulmonary function tests ( PFT ) . METHODS Eighty-two postmenopausal women who were having natural or surgically initiated menopause and had no risk factor that could affect the respiratory system were included into this prospect i ve , r and omized study . Twenty-five women who refused to use HT were assessed as the control group ( Group I ) . Nineteen women who accepted using HT and who were having surgically initiated menopause were given continuous estrogen ( Group II ) , 23 were given continuous estrogen and progesterone in combination ( Group III ) and 15 were given cyclic estrogen and progesterone combination ( Group IV ) . Forced expiratory volume ( FEV1 ) , forced vital capacity ( FVC ) , FEV1/FVC , forced expiratory flow rate over 25 - 75 % of the forced vital capacity volume and peak expiratory flow rate were assessed at the beginning of the treatment and in the third month in order to evaluate the effects of HT regimens on the women 's PFT . RESULTS A statistically significant increase was observed only in the FEV1 and FVC parameters of Group III after three months of therapy ( P<0.05 ) . The comparison between pre- and posttherapy FEV1 and FVC values showed an increase in the Group IV , but the difference was not statistically significant , while there was no difference between basal and third month FEV1 and FVC values of the group receiving estrogen only . CONCLUSIONS It was seen that particularly continuous combined HT regimen positively affected the FEV1 and FVC parameters of the postmenopausal women Background For postmenopausal women , the main reason to start hormone therapy ( HT ) is to reduce menopausal symptoms and to improve quality of life ( QOL ) . The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a r and omised trial . A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy ( EPHT ) trial in 1999–2001 . Women were r and omised to blind HT , open-label HT , placebo or non-treatment arm . After one year in the trial , a question naire was mailed and 1359 women ( 75 % ) responded , 686 in the HT arms and 673 in the non-HT arms . Mean age at filling in the question naire was 59.8years . The question naire included Women 's Health Question naire ( WHQ ) to assess menopause specific QOL of middle-aged women together with a 17-item question naire on symptoms related to menopause , a question about painful intercourse , and a question about women 's self-rated health . Results After one year in the trial , fewer women in the HT arms reported hot flashes , trouble sleeping , and sweating on the symptom question naire . According to WHQ , women in the HT arms had fewer vasomotor symptoms , sleep problems , and problems with sexual behaviour , but more menstrual symptoms ;  HT had no effect on depression , somatic symptoms , memory , attractiveness , or anxiety . A smaller proportion of women reported painful intercourse in the HT arms . There were no significant differences between the trial arms in women ’s self-rated subjective health . Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms , other than vasomotor symptoms , among postmenopausal women . WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women Circulating concentrations of sex hormone-binding globulin ( SHBG ) are increased by use of oral estrogen . The objective of this study was to determine whether postmenopausal women who used oral estrogen  had higher serum concentrations of SHBG and lower serum concentrations of free testosterone ( T ) than nonusers , and whether free T was associated with lean body mass , particularly skeletal muscle mass . Subjects were 70 postmenopausal women , 46 - 55 yr old , 46 of whom used oral estrogen .  Total and regional body composition were determined by dual-energy x-ray absorptiometry .  Serum concentrations of SHBG , total T , and estradiol ( E(2 ) ) were determined by RIA .  Free T was calculated from concentrations of total T and SHBG .  Hormone users had higher serum concentrations of E(2 ) and SHBG ( 182.0 + /- 58 . 5 vs. 82.9 + /- 41.1 nmol/L , mean + /- SD , P : < 0.001 ) and lower concentrations of free T ( 3.7 + /- 2.2 vs. 7.9 + /- 4.1 pmol/L , mean + /- SD , P : < 0.001 ) ; total T did not differ . Total lean mass and leg lean mass were significantly correlated with free , but not total T [ r values of 0.29 ( P : < 0.05 ) and 0.31 ( P : < 0.01 ) for total and leg lean mass , respectively , vs. free T ] ; arm lean mass was not correlated with either measure of T. Serum E(2 ) was significantly correlated with SHBG ( r = 0.50 , P : < 0.001 ) and free T ( r = -0.33 , P : < 0.01 ) . These observations imply that , by reducing the concentration of bioavailable T , oral estrogen therapy may accelerate or augment lean mass loss among postmenopausal women . This conclusion awaits confirmation by longitudinal observation UNLABELLED We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants . There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures . INTRODUCTION Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures , potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy . We prospect ively tested this hypothesis in the Study of Osteoporotic Fractures ( SOF ) . MATERIAL S AND METHODS We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline . Hip fracture analyses included 708 hip fractures ; vertebral fracture analyses included 267 incident vertebral fractures . Baseline serum estradiol and free testosterone values were available in a small subset of participants . RESULTS AND CONCLUSION There were no significant differences in age , weight , or BMD between the women who underwent postmenopausal oophorectomy ( n = 583 ) and those who did not ( n = 5712 ) . Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy . A history of postmenopausal oophorectomy was not associated with an increased risk of hip ( hazard ratio [ HR ] = 1.1 ; 95 % CI = 0.9 - 1.5 ) or vertebral fracture ( HR = 0.7 ; 95 % CI = 0.5 - 1.2 ) . The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level ( HR = 1.3 ; 95 % CI = 0.5 - 3.2 ) or serum free testosterone level ( HR = 1.7 ; 95 % CI = 0.8 - 3.7 ) to the model . In summary , postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort . These results are in contrast to previous findings , suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully eluci date d and that incidental oophorectomy after menopause should still be considered carefully in each potential patient OBJECTIVE Levels of estrogen , and rogen , and prolactin have been related to risk of postmenopausal breast cancer . However , the determinants of these hormone concentrations are not established . The purpose of this study was to examine correlates of endogenous sex hormones . RESEARCH METHODS AND PROCEDURES Associations among adiposity , physical activity , and diet and concentrations of estradiol , free estradiol , estrone , testosterone , free testosterone , sex hormone-binding globulin ( SHBG ) , and rostenedione , dehydroepi and rosterone , dehydroepi and rosterone sulfate , and prolactin were evaluated in 267 postmenopausal women r and omly selected from the Women 's Health Initiative Dietary Modification Trial . RESULTS In multiple regression analyses on log-transformed hormones , BMI was positively associated with estrone ( beta = 0.031 , p < 0.001 ) , estradiol ( beta = 0.048 , p < 0.001 ) , free estradiol ( beta = 0.062 , p < 0.001 ) , free testosterone ( beta = 0.017 , p = 0.02 ) , and prolactin ( beta = 0.012 , p = 0.02 ) and negatively associated with SHBG ( beta = -0.02 , p = 0.001 ) .  Total physical activity  ( metabolic equivalent tasks per week ) was negatively associated with concentrations of estrone , estradiol , and and rostenedione ( beta = -0.006 , -0.007 , and -0.005 , respectively , all p < or = 0.05 ) . Using a composite variable of BMI and physical activity dichotomized by median values , women with high BMI /low physical activity had a mean estrone concentration of 28.8 pg/mL , compared with 24.1 , 19.9 , and 18.4 pg/mL for women with high BMI /high physical activity , low BMI /low physical activity , and low BMI /high physical activity , respectively ( p trend < 0.001 ) . Similar trends were observed for estradiol and free estradiol and , in inverse , for SHBG . DISCUSSION These associations may , in part , explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk INTRODUCTION A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels . Treatment with topical hormones may provide relief in such women when used judiciously . AIM To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women . METHODS Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were r and omly divided into two study groups and one control group . The women in study group 1 received local estrogen cream ; study group 2 received local estrogen and testosterone cream ; the control group received nonhormonal lubricant KY gel for 12 weeks . The urogenital and sexuality score , along with the vaginal health index and the vaginal maturation index ( VMI ) , was calculated at the beginning of therapy and 12 weeks later . MAIN OUTCOME MEASURES Changes in the urogenital and sexuality score along with vaginal health index and VMI . RESULTS After 12 weeks of therapy , there was a significant improvement in all the four study parameters , which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group . Improvement in sexuality score was greatest with combined estrogen- and rogen therapy . There were no adverse effects and the therapies were well accepted without any compliance issue . CONCLUSION Local estrogen either alone or with and rogen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women Objective : This case – cohort study was design ed to examine whether total hip bone mineral density ( BMD ) is independently associated with breast cancer over and above its association with other determinants , including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin . Methods : Our study population was selected from a cohort of 8203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992 , at which time  BMD was assessed  , and  blood sample s were obtained . A total of 109 women developed breast cancer during four years of follow-up ; 173 other r and omly selected women from the larger cohort were also selected . Cox proportional hazards with robust variance adjustment was used for these analyses . Results : Relative to women in the lower fourth of the BMD distribution , the risk associated with being in the upper fourth was 2.6 ( 95 % confidence interval ( CI ) 1.1–5.8 ) . After adjusting for serum hormone levels , the corresponding relative risk was 2.5 ( 95 % CI 0.9–5.2 ) . With body mass index and number of years since menopause added to the multivariate analysis , the relative risk decreased to 1.4 ( 95 % CI 0.5–4.0 ) . Conclusions : BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates CONTEXT In postmenopausal women , endogenous bioavailable testosterone ( T ) and estradiol ( E2 ) have been positively associated , and SHBG has been negatively associated , with incident type 2 diabetes ( T2DM ) . Previous studies have not explored possible factors explaining these relationships . OBJECTIVE Our objective was to examine the association of endogenous sex hormones with incident T2DM  in postmenopausal women and possible explanatory factors . DESIGN , SETTING , AND PARTICIPANTS The Multi-Ethnic Study of Atherosclerosis ( MESA ) is a prospect i ve study that included 1612 postmenopausal women aged 45 - 84 yr , followed between the years 2000 - 2006 , who were not taking hormone replacement therapy , had no prevalent cardiovascular disease or diabetes , and had complete ascertainment of sex hormones . MAIN OUTCOME MEASURES T2DM was defined based on fasting glucose and /or treatment for diabetes . RESULTS There were 116 incident cases of diabetes during follow-up . Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG , we found significantly greater hazards of developing incident T2DM ( all P for trend < or=0.001 ) . After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance , bioavailable T was no longer associated with incident T2DM . The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models ( both P for trend < 0.02 ) . Dehydroepi and rosterone had no relationship with incident T2DM . CONCLUSIONS Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women Objective : To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy , estrogen-treated postmenopausal women . Design : Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks , with a serum total testosterone less than 1.2 nmol/L participated in a single-center , double-blind , r and omized , placebo-controlled study . All participants received transdermal testosterone , 400 & mgr;L of a 0.5 % testosterone gel , daily and were r and omized to receive either letrozole 2.5 mg/day or an identical placebo tablet . The main outcome measure was cognition , evaluated using a comprehensive battery of st and ardized neuropsychological tests , at baseline and week 16 . Results : Thirty women in each group completed the study .  Free testosterone increased from baseline in both groups , with no difference between groups . Free testosterone levels achieved were below the 90th centile for young women in 80 % of the participants at week 16 . Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study . No clinical ly significant effects of testosterone treatment were seen for attention and working memory , psychomotor speed , or executive function . Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy , all of which were unaffected by the aromatase inhibitor . Conclusions : We did not observe any effects of aromatase inhibition on cognition in healthy , estrogen-treated postmenopausal women treated with testosterone . This may be due to insufficient study power or a true lack of effect . However , our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large r and omized , controlled trials Objective : To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen replacement on sexual function , psychological well-being and self-esteem in surgically postmenopausal women . Methods : A letter of invitation to participate in the study was mailed to women who had undergone hysterectomy and bilateral oophorectomy for benign disorders during 1990 - 98 . Fifty women , 45 - 60 years old , were consecutively recruited and r and omly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily for 24 weeks . A double-blind design was chosen , with cross-over to the other regimen for another 24 weeks of treatment . Forty-four women completed the study . Outcome included scores on McCoy 's sex scale question naire , the Psychological General Well-Being index and a self-esteem question naire , at baseline and after 24 weeks of either treatment . Serum concentrations of total testosterone , sex hormone binding globulin , free testosterone , dihydrotestosterone , and rostenedione , estradiol , follicle stimulating hormone and luteinizing hormone were analyzed at baseline and after 24 weeks of both treatment regimens . Results : After 24 weeks , both treatment regimens had significantly improved some of the sexual variables . The addition of testosterone had a significantly better effect on the sex variables ' enjoyment of sex ' , ' satisfaction with frequency of sexual activity ' and ' interest in sex ' . The total McCoy score was significantly increased by both treatments , but there was a stronger effect when testosterone was also given . Although both regimens improved psychological well-being and self-esteem , we found no significant differences between testosterone-estrogen or estrogen alone at 24 weeks . Serum levels of all and rogens , with considerable individual variation , increased significantly from baseline after 24 weeks of testosterone-estrogen treatment . Supraphysiological levels were achieved in a significant proportion of the women . Increases in estradiol and sex hormone binding globulin were less marked when testosterone was also given . Both treatments reduced gonadotropin levels . Conclusions : The addition of testosterone undecanoate improved specific aspects of sexual function more than treatment with estrogen alone . Improvements in well-being and self-esteem were similar for both treatments . If testosterone undecanoate 40 mg daily should be used for clinical treatment , regular monitoring of and rogen serum levels is needed BACKGROUND AND OBJECTIVES In postmenopausal women , ovarian stromal hyperplasia and endometrial cancer are often identified concurrently . The aim of the present study was to verify the association of ovarian volume with histologic findings and sex hormones levels in women with postmenopausal bleeding and thickened endometrium . DESIGN AND SETTING Prospect i ve observational study conducted in a teaching hospital between March 2008 and February 2010 PATIENTS AND METHODS Ninety women with postmenopausal bleeding and thickened endometrium ( ≥5 mm ) were enrolled . They underwent vaginal sonography for ovarian volume measurement . Blood sample s were collected for  sex steroid hormones assay . In addition , endometrial sampling was done for definitive histologic diagnosis . RESULTS According to histologic results , 18 cases ( 20 % ) had endometrial adenocarcinoma , 24 cases ( 26.7 % ) had endometrial hyperplasia with or without atypia and 48 cases ( 53.3 % ) had benign histologic findings . Large ovaries were significantly associated with higher body mass index ( BMI ≥30 ) ( P=.002 ) and endometrial adenocarcinoma ( P<.001 ) . After adjustment for age and BMI , increased ovarian volume in adenocarcinoma was associated with high serum level of estradiol ( P<.001 ) , serum total testosterone ( P=.04 ) and serum free testosterone ( P<.01 ) compared with other histologic findings . CONCLUSIONS Large ovaries among women with postmenopausal bleeding and thick endometrium were associated with elevated serum sex steroid hormones and represent a marker of risk for endometrial adenocarcinoma Background : It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer ’s disease ( AD ) . Objective : To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women . Methods : Participants within 5–36 months past menopause in the Kronos Early Estrogen Prevention Study , a r and omized , double blinded placebo-controlled clinical trial , were r and omized to : 1 ) 0.45 mg/day oral conjugated equine estrogens ( CEE ) ; 2 ) 50μg/day transdermal 17β-estradiol ; or 3 ) placebo pills and patch for four years . Oral progesterone ( 200 mg/day ) was given to active treatment groups for 12 days each month . 11C Pittsburgh compound B ( PiB ) PET imaging  was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post r and omization and three years after stopping r and omized treatment . PiB St and ard unit value ratio ( SUVR ) was calculated . Results : Women ( age = 52–65 ) r and omized to transdermal 17β-estradiol ( n = 21 ) had lower PiB SUVR compared to placebo ( n = 30 ) after adjusting for age [ odds ratio ( 95 % CI ) = 0.31(0.11–0.83 ) ] . In the APOE ɛ4 carriers  , transdermal 17β-estradiol treated women ( n = 10 ) had lower PiB SUVR compared to either placebo ( n = 5 ) [ odds ratio ( 95 % CI ) = 0.04(0.004–0.44 ) ] , or the oral CEE treated group ( n = 3 ) [ odds ratio ( 95 % CI ) = 0.01(0.0006–0.23 ) ] after adjusting for  age  . Hormone therapy was not associated with PiB SUVR in the APOE ɛ4 non-carriers . Conclusion : In this pilot study , transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition , particularly in APOE ɛ4 carriers . This finding may have important implication s for the prevention of AD in postmenopausal women , and needs to be confirmed in a larger sample OBJECTIVE To determine the effect of the and rogen supplementation of hormone replacement therapy ( HRT )  on the vascular reactivity of cerebral arteries . DESIGN Open r and omized study . SETTING Healthy volunteers in an academic research environment . PATIENT(S ) Forty postmenopausal women who were treated with sequential HRT ( transdermal E2 50 microg/d + medroxyprogesterone acetate 10 mg/d for 12 days every other month ) for > or = 1 year and < or = 5 years . INTERVENTION(S ) Testosterone undecanoate ( 40 mg/d , p.o . ) was r and omly administered to 20 patients during ongoing HRT ;  the other 20 served as controls . Doppler evaluations of the internal carotid and middle cerebral arteries were performed together with lipid levels assessment s. A visual analogue scale ( VAS ) was used to evaluate various parameters relating to sexual life and well-being . MAIN OUTCOME MEASURE(S ) Pulsatility index ( PI ) of the arteries , VAS assessment of psychophysical well-being . RESULT ( S ) The administration of testosterone undecanoate during HRT induced an increase in the PI of the middle cerebral artery and a reduction of high-density lipoprotein cholesterol . Sexual desire and satisfaction were greatly improved . CONCLUSION ( S ) In postmenopausal women , and rogen supplementation during HRT can partially counteract the beneficial effects of estrogens on cerebral vascular reactivity and lipid profiles , but sexual desire and satisfaction are greatly improved BACKGROUND Alcohol ingestion is associated with an increased risk of breast cancer  in most epidemiologic studies . Results , however , are heterogeneous at lower levels of alcohol intake , and a biologic mechanism for the association has not been clearly identified . To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer , we performed a controlled feeding study . METHODS Participants were 51 healthy postmenopausal women not using hormone replacement therapy . Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage . The order of assignment to the three alcohol levels was r and om . During the dietary periods , all food and beverages were supplied by the study , and energy intake was adjusted to keep body weight constant . Levels of estradiol , estrone , estrone sulfate , testosterone , and rostenedione , progesterone , dehydroepi and rosterone ( DHEA ) , DHEA sulfate ( DHEAS ) , and and rostenediol were measured by radioimmunoassays in serum collected at the end of each dietary period . All statistical tests are two-sided . RESULTS When women consumed 15 or 30 g of alcohol per day , respectively , estrone sulfate concentrations increased by 7.5 % ( 95 % confidence interval [ CI ] = -0.3 % to 15.9 % ; P = .06 ) and 10.7 % ( 95 % CI = 2.7 % to 19.3 % ; P = .009 ) and DHEAS concentrations increased by 5.1 % ( 95 % CI = 1.4 % to 9.0 % ; P = .008 ) and 7.5 % ( 95 % CI = 3.7 % to 11.5 % ; P<.001 ) relative to levels when women consumed placebo . None of the other hormones measured changed statistically significantly when women consumed alcohol . CONCLUSIONS Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk , and this association is strongly supported by experimental studies using laboratory animals and model systems . Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited ; however , beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence . This study examined whether baseline serum concentrations of estradiol , testosterone , and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a r and omized diet trial ( Women 's Healthy Eating and Living Study ) who were followed for > 7 years after diagnosis . In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis , total estradiol [ hazard ratio ( HR ) , 1.41 per unit increase in log concentration ; 95 % confidence interval ( 95 % CI ) , 1.01 - 1.97 ] , bioavailable estradiol ( HR , 1.26 ; 95 % CI , 1.03 - 1.53 ) , and free estradiol ( HR , 1.31 ; 95 % CI , 1.03 - 1.65 ) concentrations were significantly associated with risk for recurrence . Recurred women had an average total estradiol concentration that was double that of nonrecurred women ( 22.7 versus 10.8 pg/mL ; P = 0.05 ) . Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence . Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk , results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(3):614–20 BACKGROUND A positive relationship has generally been observed between plasma estrogen levels and  breast cancer risk in postmenopausal women , but most of these studies have been small and few have evaluated specific estrogen fractions ( such as percent bioavailable estradiol ) . In addition , few studies have evaluated plasma and rogen levels in relation to breast cancer risk , and their results have been inconsistent . We prospect ively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses ' Health Study . METHODS Blood sample s were collected during the period from 1989 through 1990 . Among postmenopausal women not using hormone replacement therapy at blood collection ( n = 11,169 women ) , 156 women were diagnosed with breast cancer after blood collection but before June 1 , 1994 . Two  control  subjects were selected per case subject and matched with respect to age , menopausal status , month and time of day of blood collection , and fasting status at the time of blood collection . RESULTS From comparisons of highest and lowest ( reference ) quartiles , we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol ( multivariate relative risk [ RR ] = 1.91 ; 95 % confidence interval [ CI ] = 1.06 - 3.46 ) , estrone ( multivariate RR = 1.96 ; 95 % CI = 1.05 - 3.65 ) , estrone sulfate ( multivariate RR = 2.25 ; 95 % CI = 1.23 - 4.12 ) , and dehydroepi and rosterone sulfate ( multivariate RR = 2.15 ; 95 % CI = 1.11 - 4.17 ) . We found no substantial associations with percent free or percent bioavailable estradiol , and rostenedione , testosterone , or dehydroepi and rosterone . The positive relationships were substantially stronger among women with no previous hormone replacement therapy . CONCLUSION Our data , in conjunction with past epidemiologic and animal studies , provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer BACKGROUND Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk . Whether mammographic density reflects levels of endogenous sex hormones is unclear . We examined whether these predictors are independently associated with breast cancer risk in a prospect i ve study . METHODS We conducted a nested case-control study within the Nurses ' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects . All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography .  Plasma levels of estradiol , free estradiol , testosterone , and free testosterone were evaluated .  Mammographic density was assessed by use of computer-assisted analysis of mammograms . Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk . The relative risk of breast cancer associated with mammographic density ( RR for highest quartile compared with lowest quartile = 3.8 , 95 % CI = 2.2 to 6.6 ; P(trend)<.001 ) changed little when the analysis was adjusted for circulating estradiol ( RR = 3.9 , 95 % CI = 2.2 to 6.9 ; P(trend)<.001 ) or circulating testosterone ( RR = 4.1 , 95 % CI = 2.3 to 7.2 ; P(trend)<.001 ) . Circulating levels of estradiol ( RR = 2.4 , 95 % CI = 1.4 to 4.0 ) and of testosterone ( RR = 2.0 , 95 % CI = 1.2 to 3.1 ) were both associated with breast cancer risk , before and after adjustment for mammographic density . In a joint analysis of mammographic density and plasma testosterone , the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both ( RR = 6.0 , 95 % CI = 2.6 to 14.0 ) . A similar pattern was observed in the joint analysis of estradiol and mammographic density ( RR = 4.1 , 95 % CI = 1.7 to 9.8 ) . CONCLUSIONS Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women OBJECTIVE To determine the prospect i ve association between endogenous sex hormones and the development of  type 2 diabetes in older men and women . RESEARCH DESIGN AND METHODS A st and ardized medical history was obtained , an oral glucose tolerance test was performed , and plasma sample s for sex hormones and covariates were collected from ambulatory , community-dwelling men and women at baseline from 1984 to 1987 . Approximately 8 years later ( 1992 - 1996 ) , another medical history was obtained , an oral glucose tolerance test was performed , fasting and 2-h insulin levels were measured , and the homeostasis model assessment for insulin resistance ( HOMA-IR ) was evaluated . This report is based on the 294 men and 233 women , aged 55 - 89 years , who completed both visits and who did not have diabetes as determined by history or glucose tolerance test at baseline , as well as women who were postmenopausal and not taking replacement estrogen . RESULTS In age-adjusted correlation analyses , total testosterone was inversely and significantly related to subsequent levels of fasting and postchallenge glucose and insulin in men , whereas bioavailable testosterone and bioavailable estradiol were positively and significantly related to fasting and postchallenge glucose and insulin in women ( all P < 0.05 ) . There was similar significant association with insulin resistance ( HOMA-IR ) in unadjusted and multiply adjusted analyses ( P < 0.05 ) . There were 26 men and 17 women with new ( incident ) diabetes .  The odds for new diabetes were 2.7 ( 95 % CI 1.1 - 6.6 ) for men in the lowest quartile of total testosterone and 2.9 ( 1.1 - 8.4 ) for women in the highest quartile of bioavailable testosterone . CONCLUSIONS Low testosterone levels in men and high testosterone levels in women predict insulin resistance and incident type 2 diabetes in older adults OBJECTIVE To evaluate the effects of a non-prescription red clover extract ( MF11 RCE , Melbrosin International , Vienna , Austria ) on selected sex hormones and endometrium in postmenopausal women . PATIENTS AND METHODS One-hundred and nine postmenopausal women with an age > or = 40 years were r and omly assigned to one of two groups either two capsules of MF11RCE ( 80 mg isoflavone ) per day for a 90 day period , or placebo of equal design . After a 7 day washout period , medication was crossed-over for another 90 days . RESULTS Combined evaluation demonstrated that supplementation with MF11RCE ( verum ) , in contrast to placebo , significantly increased plasma testosterone levels and decreased endometrial thickness . CONCLUSION MF11RCE exerts a moderate effect on testosterone levels in postmenopausal women , while estradiol levels remained unchanged . The observed reduction of endometrial thickness provides further support for a safe role for isoflavones in terms of endometrial hyperplasia We wished to investigate if a testosterone gel administered percutaneously to postmenopausal women could result in stable serum levels of the hormone and which dose was required to produce levels within the normal premenopausal range . Fifteen postmenopausal women , mean age 55.3 years ( range 45–70 years ) , volunteered to participate in the study and were divided into three groups . They received 10 , 20 or 30 mg of testosterone as a 1 % testosterone hydroalcoholic gel at 09.00 hours daily for 14 days . The gel was applied in a thin layer on the outside of the thigh each morning , over an area of approximately 15 cm2 . Blood sample s were collected hourly between 09.00 and 17.00 hours on days 1 and 14 , and also at 08.00 hours on days 3 , 5 , 11 , 12 , 13 and finally day 16 , i.e. 2 days after termination of treatment . The mean basal serum level of testosterone was 1.1 ± 0.9 nmol/l and for 5α-dihydrotestosterone 208 ± 143 pmol/l . There was a clear increase from the 10 mg to the 20 mg treatment ( mean testosterone level during treatment 3.2 and 7.2 nmol/l , respectively ) while serum testosterone values after 30 mg showed very little further increase ( mean 7.5 nmol/l ) . Values for days 3–5 were quite similar to those for days 13–14 . The present study suggests that adequate and acceptable serum levels of testosterone can be achieved with 10 mg testosterone applied transdermally In this paper , the association of hormones to vasomotor complaints during the menopausal transition is discussed . Fifty-seven regularly menstruating women without history of hormone replacement therapy ( HRT )  were selected for a longitudinal , prospect i ve study around the menopausal transition . The mean age at the start of the study was 51.3 ( + /-2.0 ) years . At intervals of 12 months all women went through a semi-structured interview and filled in question naires .  Venous blood sample s were collected every 12-month for analyses of estradiol ( E2 ) , testosterone , and rostendione , dehydroepi and rosterone-sulphate ( DHEA-S ) , follicle stimulating hormone ( FSH ) , thyrotropin ( TSH ) , and luteinizing hormone ( LH ) . Vasomotor complaints were tested using questions about hot flushes and bouts of sweating in terms of occurrence , frequency and degree of distress . Forty-six percent of the subjects reported hot flushes and bouts of sweating before menopause , increasing to 67 % during the first year after menopause and 49 % in the second year postmenopause . Low levels of estradiol and high levels of FSH were associated with vasomotor complaints before menopause . During menopause high levels of TSH were related to vasomotor complaints . The first year after menopause , women , who at this point achieved hot flushes , were characterised by high levels of E2 , but declining and low levels of FSH , but increasing . Postmenopausal , high levels of testosterone and DHEA-S seemed to protect against vasomotor symptoms . Our most important finding was , that among women who achieved hot flushes at the first assessment postmenopause , the high and rogen levels was a significant predictor of recovery from hot flushes at the last assessment , 1 year later OBJECTIVE To test the causal relationship between sex hormones and cognitive skills in postmenopausal women . We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo . For estrogen , we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability . DESIGN R and omized , double-blind , placebo-controlled , parallel-group trial . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Two-hundred healthy , naturally postmenopausal women aged 50 - 65 years . INTERVENTION(S ) R and omization to 4 weeks ' treatment with testosterone ( testosterone undecanoate , 40 mg/day ) , estrogen ( oral E2 2 mg/day ) or placebo . MAIN OUTCOME MEASURE(S ) Comparisons in verbal fluency , verbal memory , and spatial ability between the three treatment groups . RESULT ( S ) We found no significant effects of testosterone or estrogen on verbal fluency , verbal memory , or spatial ability . CONCLUSION ( S ) Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency , verbal memory , or spatial ability in healthy postmenopausal women Background With the exception of sexual functioning and weight , social and behavioural effects of postmenopausal hormone therapy ( HT ) have not been reported from trials . This paper reports such results from the EPHT-trial in Estonia . Methods A r and omized trial , with a blind and non-blind sub-trial in Estonia . From 1999–2001 , 1778 women were recruited . The mean follow-up was 3.6 years . Women 's experiences were asked in the first and final study year by mailed question naires ( 74 and 81 % response rates ) . Comparisons of the groups were made by cross-tabulation and logistic regression , adjusting for age . Results There were no differences between the HT and non-HT groups in regard to being employed , the extent of social involvement or marital status or opinions on aging . There was no difference in the frequency of free-time exercise , or overweight . Some of the indicators suggested less sexual inactivity , but the differences were small . Conclusion In a trial setting , postmenopausal hormone therapy did not influence work or social involvement or health behaviour . Trial registration IS RCT Introduction Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy ( HT ) . We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes . Methods Healthy , non-smoking freshly postmenopausal women ( n = 150 ) with no previous HT use were studied . Seventy-two women reported intolerable hot flushes ( ≥7 moderate/severe episodes/day ) and 78 women tolerable hot flushes ( ≤3 mild episodes/day ) . The participants were treated in r and omized order with either transdermal estradiol gel ( 1 mg ) , oral estradiol valerate ( 2 mg ) with or without medroxyprogesterone acetate ( 5 mg ) , or placebo for 6 months . Treatment-induced changes in lipids , lipoproteins , apolipoproteins , sex hormone binding globulin ( SHBG ) and high-sensitivity C-reactive protein were compared . The trial is registered in the US National Institutes of Health Clinical Research Registry ( no. NCT00668603 ) . Results Pretreatment hot flush status was not related to the responses of these markers to different forms of HT . However , when all active regimens were evaluated together as a post-hoc analysis , 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes . Furthermore , in women with intolerable hot flushes and with HT use , the increases in SHBG ( Spearman 's rho = − 0.570 , p < 0.001 ) were related to the reductions in hot flushes during the use of HT . Conclusions Hot flushes appear to be no significant determinant for the responses of vascular  markers to HT use Recent reports suggest that soy protein may reduce the risk of osteoporosis in peri- and postmenopausal women . The objective of this study was to examine whether soy supplementation exerts beneficial effects on serum and urinary biomarkers of bone metabolism in postmenopausal women , regardless of whether or not they are on hormone replacement therapy ( HRT ) . A total of 71 women were r and omly assigned to either soy protein ( SP ) or milk-based protein ( MBP ) , 40 g daily for 3 months , in a double-blind parallel design . Forty-two women completed the study ( 20 on SP and 22 on MBP ) . Overall , both protein supplements positively influenced serum IGF-I , known to correlate with bone formation . However , SP had a more pronounced effect on IGF-I than MBP . Urinary deoxypyridinoline ( Dpd ) excretion , a specific biomarker of bone resorption , was significantly reduced by SP , but not by MBP when all women were included . Furthermore , women on MBP experienced a 33 % increase in urinary calcium excretion , whereas SP did not have such an effect . To evaluate whether SP affects women differently on the basis of their HRT status , data from women on HRT ( n = 22 ) and those not on HRT ( n = 20 ) were analyzed separately . The sub analysis of the data indicated that SP had the greatest impact on serum IGF-I ( an increase of 97 % ) in the women not on HRT . The changes in urinary Dpd due to SP were only observed in women not on HRT , indicating that the overall decrease in Dpd occurred with SP in the absence of HRT . These results indicate that soy protein may positively influence bone and calcium homeostasis in postmenopausal women , particularly those not on HRT 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 , r and omized , controlled , clinical trial was conducted . A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were r and omized into one of three groups . In all groups , participants consumed a daily supplement containing 25 g of soy protein and were r and omly 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 Objective : The extent to which aromatization of testosterone ( T ) to estradiol is required for the observed effects of testosterone therapy on sexual function and well-being are not known . Therefore , the authors investigated the effects of aromatase enzyme inhibition on sexual function , well-being , and mood in estrogen- and T-replete postmenopausal women in a double-blind , r and omized , placebo-controlled study . Design : Postmenopausal women using transdermal estrogen therapy for at least 8 weeks and reporting low sexual satisfaction ( score < 42 for the Sabbatsberg Sexual Self-rating Scale [ SSS ] ) with a total T value of less than 1.2 nmol/L were treated with 400 μL of a 0.5 % T gel ( total dose 2 mg ) and were r and omly assigned to receive treatment with either 2.5 mg/day of letrozole or an identical placebo tablet . Women were assessed at baseline ( week −2 ) and at 0 , 4 , 8 , and 16 weeks . Sexual function was assessed with the SSS , well-being was assessed with the Psychological General Well-being Index , and mood was assessed with the Beck Depression Inventory at 0 and 16 weeks . Eighty-one women were screened , 76 were r and omly assigned to a treatment group , and 30 in each group completed the study . Because this was a mechanistic study , only the 60 women who completed the study per protocol were included in the final analysis . Results : Total T and calculated free T increased from baseline in both groups , with no difference between groups . At 16 weeks , estradiol , sex hormone-binding globulin , fasting lipids , lipoprotein(a ) , and C-reactive protein did not differ from baseline or between groups . Significant increases in total Sabbatsberg Sexual Self-rating Scale scores , total Psychological General Well-being Index scores , and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was seen for both treatment groups , with no effect of treatment allocation . No adverse treatment effects were reported . Conclusions : Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction , well-being , and mood . In this study , aromatase inhibition did not influence any of these outcomes . Short-term transdermal T therapy did not modify fasting lipids , lipoprotein(a ) , or C-reactive protein Objective : We examined whether circulating concentrations of sex hormones , including estradiol , testosterone , sex hormone – binding globulin ( SHBG ) , and dehydroepi and rosterone sulfate ( DHEAS ) , were associated with alcohol intake or mediated the alcohol – type 2 diabetes ( T2D ) association . Methods : Among women not using hormone replacement therapy and free of baseline cardiovascular disease , cancer , and diabetes in the Women 's Health Study , 359 incident cases of T2D and 359 matched controls were chosen during 10 years of follow-up . Results : Frequent alcohol intake ( ≥1 drink/day ) was positively and significantly associated with higher plasma estradiol concentrations in an age-adjusted model ( β = 0.14 , 95 % confidence interval [ CI ] , 0.03 , 0.26 ) , compared to rarely/never alcohol intake . After adjusting for additional known covariates , this alcohol – estradiol association remained significant ( β = 0.19 , 95 % CI , 0.07 , 0.30 ) . Testosterone ( β = 0.13 , 95 % CI , −0.05 , 0.31 ) , SHBG ( β = 0.07 , 95 % CI , −0.07 , 0.20 ) , and DHEAS ( β = 0.14 , 95 % CI , −0.04 , 0.31 ) showed positive associations without statistical significance . Estradiol alone or in combination with SHBG appeared to influence the observed protective association between frequent alcohol consumption and T2D risk , with a 12%–21 % reduction in odds ratio in the multivariate-adjusted models . Conclusions : Our cross-sectional analysis showed positive associations between alcohol intake and endogenous estradiol concentrations . Our prospect i ve data suggested that baseline concentrations of estradiol , with or without SHBG , might influence the alcohol – T2D association in postmenopausal women BACKGROUND Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial , but the presence of osteoporosis is regarded as an indication for parathyroidectomy . Hormone replacement therapy ( HRT ) is a possible alternative therapy in osteopenic postmenopausal women with the disorder , and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy . Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism . METHODS We report the results of the extension from 2 to 4 years of a r and omized , placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism . Of 23 postmenopausal women with primary hyperparathyroidism , 11 received active HRT with conjugated equine estrogen , 0.625 mg/d , and medroxyprogesterone acetate , 5 mg/d , and 12 received placebo .  Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects . None of the 23 patients withdrew during the extension period . RESULTS Changes in bone mineral density were more positive in those taking HRT than placebo , with the between-group differences at 4 years being 4.6 % in the total body , 7.5 % in the lumbar spine , 7.4 % in the femoral neck , 8.2 % in the femoral trochanter , 6.8 % in the legs , and 7.0 % in the forearm ( P<.01 ) . At skeletal sites composed predominantly of cortical bone , there was a progressive divergence of the 2 groups . Biochemical markers of bone turnover remained lower throughout the study in women taking HRT . When rates of bone loss were compared between the placebo group and healthy women of comparable age , bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism , but only in the total body and its legs subregion was this difference significant . CONCLUSIONS Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery .  Bone loss seems to be accelerated in untreated primary hyperparathyroidism BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy  are unknown . METHODS We conducted a double-blind , placebo-controlled , 52-week trial in which 814 women with hypoactive sexual desire disorder were r and omly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo .  Efficacy was measured to week 24 ; safety was evaluated over a period of 52 weeks , with a subgroup of participants followed for an additional year . The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes . RESULTS At 24 weeks , the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group ( an increase of 2.1 episodes vs. 0.7 , P<0.001 ) but not in the group receiving 150 microg per day ( 1.2 episodes , P=0.11 ) . As compared with placebo , both doses of testosterone were associated with significant increases in desire ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) and decreases in distress ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) . The rate of and rogenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group ( 30.0 % vs. 23.1 % ) . Breast cancer was diagnosed in four women who received testosterone ( as compared with none who received placebo ) ; one of the four received the diagnosis in the first 4 months of the study period , and one , in retrospect , had symptoms before undergoing r and omization . CONCLUSIONS In postmenopausal women not receiving estrogen therapy  , treatment with a patch delivering 300 microg of testosterone per day result ed in a modest but meaningful improvement in sexual function . The long-term effects of testosterone , including effects on the breast , remain uncertain . ( Clinical Trials.gov number , NCT00131495 . Objective : To evaluate vaginal , endometrial , and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy ( HT ) . Design : This was a 1-year , r and omized , double-blind , placebo-controlled trial of 351 women , ages 45 to 55 , with two or more vasomotor symptoms per day . Women were r and omly assigned to ( 1 ) black cohosh , ( 2 ) a multibotanical containing black cohosh , ( 3 ) the same multibotanical plus dietary soy counseling , ( 4 ) HT , or ( 5 ) placebo .  Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month . Data on vaginal cytology and dryness were collected ( at baseline and 3 and 12 mo ) . Daily menstrual diaries were maintained by 313 women with a uterus , and abnormal bleeding was evaluated . Serum estradiol , follicle-stimulating hormone , luteinizing hormone , and steroid hormone-binding globulin were assessed ( baseline and 12 mo ) among 133 postmenopausal women . Gynecologic outcomes of the five groups were compared . Results : The five groups did not vary in baseline vaginal cytology profiles , vaginal dryness , menstrual cyclicity , or hormone profiles . The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months ( P < 0.05 ) . Abnormal bleeding occurred in 53 of 313 ( 16.9 % ) women . There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups , whereas women in the HT group had a greater risk than those in the placebo group ( P < 0.001 ) . Among postmenopausal women , HT significantly decreased follicle-stimulating hormone and increased estradiol ; none of the herbal interventions showed significant effects on any outcomes at any time point . Conclusion : Black cohosh , used alone or as part of a multibotanical product with or without soy dietary changes , had no effects on vaginal epithelium , endometrium , or reproductive hormones OBJECTIVE To evaluate the effects of combination estrogen/ and rogen therapy on muscle mass , strength and endurance , serum hormone and lipid profiles , and quality of life measures in postmenopausal women . METHODS Prospect i ve , r and omized , placebo-controlled pilot study at a tertiary care medical center . Fifty postmenopausal women were r and omized to a 12-week course of ( 1 ) dehydroepi and rostenedione ( DHEA ) 50 mg daily , ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily , ( 3 ) DHEA 50 mg+CEE 0.625 mg daily , or ( 4 ) placebo . Main outcome measures of lower extremity muscle ( calf ) mass , functional muscle parameters , serum hormone and lipid levels , and quality of life ( QOL ) were obtained at baseline and after treatment . Statistical analysis compared percent change from baseline values and treatment differences among outcomes . RESULTS Significant increases in mean DHEA , DHEA sulfate ( DHEA-S ) , testosterone , and and rostenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo . Compared with no hormone therapy , none of the supplemental hormone groups caused significant changes in muscle mass , muscle strength , muscle endurance , feelings of well-being , sleep , or sexual function . CONCLUSIONS And rogen replacement therapy , with DHEA , to menopausal women increases serum and rogen levels without any appreciable effect on muscle cross-sectional area , muscle strength , muscle function , or improvement in health-related QOL
The pooled estimate from the studies suggested that the addition of testosterone to HT regimens improved sexual function scores for postmenopausal women .
A significant adverse effect was a decrease in high-density lipoprotein ( HDL ) cholesterol levels .
However , there is evidence that adding testosterone to HT has a beneficial effect on sexual function in postmenopausal women .
There was a reduction in HDL cholesterol associated with the addition of testosterone to the HT regimens .
It is , therefore , difficult to estimate the effect of testosterone on sexual function in association with any individual hormone treatment regimen
BACKGROUND : The value of adding testosterone to hormone therapy ( HT ) for the management of peri- and postmenopausal women is controversial and has not been systematic ally review ed .
OBJECTIVES : To determine the benefits and risks of testosterone therapy for peri- and postmenopausal women taking hormone therapy .