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A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms Hormone therapy in menopausal women with cognitive complaints Women's willingness to accept perceived risks for vasomotor symptom relief. Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study. Short-term hormone therapy improves sCD40L and endothelial function in early menopausal women: potential role of estrogen receptor polymorphisms. 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Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. Managing menopause. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: a double-blind, randomised study. Hormonal and psychological treatment: therapeutic alternative for menopausal women? Continuous combined hormone replacement therapy compared with tibolone. A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule (和颜坤泰胶囊) and Hormone Therapy in Perimenopausal Women The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. 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Several formulations combining estrogens and progestins for hormone therapy ( HT ) have been approved worldwide for the treatment of menopausal symptoms , yet recent data indicate a decline in their use and an increase in compounded bioidentical HT . Up to now , no single product combining natural 17β-estradiol and progesterone has been approved by the US Food and Drug Administration ( FDA ) or the European Medicines Agency ( EMA ) . A phase 3 trial ( REPLENISH ) is underway to study a novel oral formulation of solubilized 17β-estradiol and natural progesterone combined in a single gelatin capsule ( TX-001HR ; TherapeuticsMD , Inc , Boca Raton , FL ) for treating vasomotor symptoms ( VMS ) in postmenopausal women . The REPLENISH trial evaluates the efficacy and safety of TX-001HR ( 4 doses ) versus placebo for the reduction of moderate to severe VMS frequency and severity at 4 and 12 weeks and evaluates the endometrial safety of the combinations at 1 year . TX-001HR contains hormones that are molecularly identical to endogenous estradiol and progesterone and is intended as an option for women who prefer bioidentical hormones ; further , it does not contain peanut oil , a common allergen . The constituents of TX-001HR , in a pharmacokinetic report , showed similar bioavailability and safety compared with reference estradiol tablets and micronized progesterone capsules administered together . Published data suggest a safer profile of estradiol and natural progesterone compared with HT containing conjugated equine estrogens and progestins . This report summarizes the methodology of the REPLENISH trial and review s the evidence suggesting clinical differences between HT containing progesterone or progestins , and estradiol or conjugated equine estrogens Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy ; however , clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking . The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor , mood , and other quality -of-life symptoms in post-menopausal women . This was a prospect i ve , observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1 , 2003 and October 1 , 2010 in a community pharmacy . Data collection included patient demographics , comorbidities , hormone regimens , and therapeutic outcomes . Patients rated their vasomotor , mood , and quality -of-life symptoms as absent , mild , moderate , or severe at baseline , at one to three months follow-up , and three to six months follow-up . Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables . Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test . A total of 200 patients met study criteria ; 160 received topical bioidentical hormone replacement therapy  , and 40 received sublingual bioidentical hormone replacement therapy . Most sublingually-treated patients ( 70 % ) received an estrogen combination and 100 % received progesterone . Nearly half ( 43 % ) of the topically treated patients received an estrogen combination ( 43 % ) and 99 % received progesterone . The percentage of sublingually treated patients reporting " moderate " or " severe " symptoms was significantly reduced at one to three months follow-up for the following target symptoms : hot flashes ( 31 % , P = 0.04 ) , night sweats ( 38 % , P < 0.01 ) , irritability ( 36 % , P = 0.01 ) , anxiety ( 42 % , P < 0.01 ) , emotional lability ( 38 % , P < 0.01 ) , sleep disturbances ( 35 % , P < 0.01 ) , memory loss ( 35 % , P = 0.04 ) , fatigue ( 33 % , P = 0.04 ) , and libido ( 26 % , P = 0.03 ) . Similar reductions were seen at three to six months follow-up compared to baseline . Patients who received topical therapy did not experience significant symptom reductions at one to three months follow-up ; however , significant symptom reduction was seen at three to six months for the following : emotional lability ( 31 % , P < 0.01 ) , irritability ( 29 % , P = 0.02 ) , and night sweats ( 20 % , P = 0.04 ) . Compounded sublingual bioidentical hormone replacement therapy is effective in reducing vasomotor , mood , and quality -of-life symptoms experienced in post-menopausal women .  Topical therapy does not appear to improve symptoms as extensively or rapidly as sublingual therapy OBJECTIVE The aim of this study was to assess pharmacists ' beliefs about bioidentical hormone therapy ( BHT ) and to identify factors influencing these beliefs . STUDY DESIGN This was a cross-sectional survey of pharmacists . An email invitation to participate in the online survey  was sent to a r and om sample of 2000 pharmacists in Alberta . The survey was accessible for a six-week period from May to July , 2011 . A 54-item question naire was used to capture knowledge and beliefs about , and confidence in BHT . Summary statistics and multivariate regression were used for analyses . RESULTS Overall , 401 pharmacists completed the survey ( response rate 20 % ) . Respondents were mainly female ( 64 % ) , above 30 years of age ( 81 % ) and in practice for more than 10 years ( 63 % ) . Only 35 % of respondents correctly classified BHT as including both compounding and commercial products . In regards to beliefs , 68 % of respondents agreed that BHT is as effective as non-bioidentical hormones for vasomotor symptoms , while 60 % agreed BHT had equal risk . Beliefs on estriol , progesterone , and saliva testing however , were more diverse with many " do not know " responses ( 40 % ) . In multivariate analysis , pharmacists who worked in pharmacies that compounded BHT were more likely to believe in BHT safety ( p<0.001 ) , and have greater confidence with BHT ( p<0.001 ) . CONCLUSIONS Results from this survey indicated that pharmacists had varying beliefs on BHT . In addition , beliefs on the safety of BHT were associated with pharmacists ' practice , specifically working in a pharmacy that compounds BHT . This study helps identify areas for targeted education Objective : To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system ( lipophilic emulsion-type base ) to relieve  climacteric symptoms . The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern . Design : An open , r and omized , comparative , between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments . Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months . Pharmacokinetic data following transdermal administration of 17β-estradiol ( 0.3 mg , daily ) and progesterone ( 100 mg , daily ) were calculated from saliva levels using high-performance liquid chromatography analysis . Results : Improvement in climacteric symptoms was reported in 93 % of women evaluated before and after 3 and 6 months of treatment . Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL , and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders , 88 % characterized symptom relief as complete . No adverse health-related events were attributed to the bioidentical hormone therapy . Time to maximum saliva concentrations ( Tmax ) , in all experimental cases , was observed after 6 hours . Baseline values were reached within 24 hours , indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period , ie , its daily biological rhythm . Conclusion : Percutaneous absorption of 17β-estradiol , as well as the absorption of progesterone , was associated with relief of climacteric symptoms . The cyclical transdermal delivery of combined bioidentical hormones may be advantageous because it mimics the secretory profiles of 17β-estradiol and progesterone in normally cyclic women over a 28-day period . Larger studies are needed to determine the long-term effects of our therapy Menopausal  Hormone Therapy ( MHT ) use in Australia fell by 55 % from 2001 to 2005 , following the release of large-scale findings on its risks and benefits . Comprehensive national data , including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey , when 11 % of women aged 45 + years were estimated to be current  MHT users . No national data are available on prevalence of use of “ bioidentical ” hormone therapy ( BHT ) . The objective of this study was to determine recent prevalence of MHT and BHT use . A cross-sectional , national , age-stratified , population survey was conducted in 2013 . Eligible women , aged 50–69 years , resident in Australia were r and omly sample d in 5-year age groups from the Medicare enrolment data base ( Australia ’s universal health scheme ) . The response rate was 22 % based on return of completed question naires , and analyses were restricted to 4,389 women within the specified age range . The estimated population -weighted prevalence of current use of MHT  was 13 % ( 95%CI 12–14 ) , which was broadly similar to the previously reported national figures in 2004–5 , suggesting that the use of MHT in Australia has largely stabilised over the past decade . A total of 39 % and 20 % of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT  , respectively , whereas 77 % of hysterectomised current-users used oestrogen-only MHT . Almost three-quarters of current-users [ population -weighted prevalence 9 % ( 95%CI 8–10 ) ] had used MHT for ≥5 years . In regard to BHT , estimated population -weighted prevalence of ever use was 6 % ( 95%CI 6–7 ) and 2 % ( 95%CI 2–3 ) for current use . The population -weighted prevalence of MHT and BHT combined , in current users in their fifties and sixties was 15 % ( 95%CI 14–16 ) . These data provide a recent national “ snapshot ” of Australian women ’s use of both conventional MHT and of BHT Background and Objective The highest level of scientific evidence available for each therapy for menopausal symptoms was sought , for example , systematic review s of r and omised controlled trials ( RCTs ) . Results There is reasonable evidence that some symptoms are modified by lifestyle , for example , cessation of smoking , exercise , reduction of alcohol , diet and alleviation of psychosocial stress . No complementary medicine , for example , phytoestrogens , black cohosh , herbal or homeopathic medicines or complementary therapies , for example , acupuncture , yoga , chiropractic manipulation , reflexology or magnetic devices have a greater effect than the usual placebo effect seen in quality blinded RCTs . Some have potential side-effects . So-called ' bioidentical hormones ' have no evidence -base and potential for harm . None of the above therapies have evidence of efficacy and long-term safety . Selective serotonin and noradrenaline re-uptake inhibitors ameliorate vasomotor symptoms and sometimes menopausal depression better than placebo . The most effective therapy for menopausal ( oestrogen ) deficiency symptoms is oestrogen which is the main component of hormone replacement therapies ( HRT ) . Compared with placebo HRT is highly effective in relieving hot flushes , night sweats , dry vagina and dyspareunia . It also improved joint pains , sexuality and sleeplessness and reduced subsequent fractures in RCTs . The increased risk of oral HRT for thromboembolism is small around menopause , for those without thrombotic risk factors , and is not elevated with non-oral routes . Cardiovascular disease may be reduced when HRT is initiated near menopause . Breast cancer risk increases after several years with the use of oral HRT containing progestogens at an annual rate of 8/10 000 ( < 0.1 % ) . No increase in breast cancer risk was seen with oestrogen-only HRT 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 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 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 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 Bioidentical compounded hormone therapy is popular among patients , but providers do not have pharmacokinetic information or dosing guidelines for these preparations . Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice . METHODS We conducted a r and omized , blinded , four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream ( Bi-est ( 80:20 ) ; 2.0 , 2.5 , or 3.0 mg)+compounded oral progesterone 100 mg , or to a conventional estradiol patch ( Vivelle-Dot ™ 0.05 mg)+Prometrium ™ 100 mg . Serum levels of estrone , estradiol , estriol , and progesterone were obtained at multiple time intervals during the first 24-h , and at steady-state . RESULTS Results were analyzable for 37/40 women .  Study medications were well tolerated . The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch . The difference was statistically significant for Bi-est 2.0 mg ( AUC-estradiol=181 vs. 956 ; p<0.001 ) and 2.5 mg ( AUC-estradiol=286 vs. 917 ; p<0.001 ) . Estriol levels remained low in all study arms . Serum progesterone levels were comparable in conventional vs. compounded groups . CONCLUSIONS This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the st and ard-dose estradiol patch . To find comparable doses , further studies are needed . This successfully conducted r and omized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial BACKGROUND Evidence suggests that a high proportion of perimenopausal and postmenopausal women experience vasomotor symptoms ( hot flushes/night sweats ) that can be severe and disruptive and which are the principal reason for seeking medical intervention . Hormone therapy ( HT ) is known to be an effective treatment for troublesome hot flushes/night sweats but research has raised questions about the safety of HT and there have been negative high profile media reports about its use . Consequently many women are seeking alternatives and exercise might be one such option but there is a lack of high quality evidence on its effectiveness . AIMS This RCT initially aims to investigate the feasibility/acceptability of two exercise interventions identified from our previous preference study in 165 women , and if found to be feasible/acceptable , continue to recruit sufficient women ( n=261 ) to examine the effect of these interventions on hot flushes/night sweats and other outcomes relevant to menopausal women . METHOD We aim to recruit inactive perimenopausal and menopausal symptomatic women not using HT and r and omise them to one of two exercise interventions or usual care for six months . RESULTS We will assess outcomes at baseline and 6 and 12 months from r and omisation . CONCLUSION We hope this RCT will contribute towards increasing the evidence regarding the question of whether exercise is an effective treatment for vasomotor symptoms in women not taking HT OBJECTIVE To investigate the recurrence and severity of climacteric symptoms after two methods of discontinuation of prolonged hormone therapy . DESIGN Postmenopausal women treated with hormone therapy for more than 3 years and opting to discontinue therapy were r and omly assigned to two treatment groups . Hormone therapy was discontinued either abruptly ( group 1 ) or gradually ( group 2 ) . Symptoms in both groups were monitored with the Greene climacteric scale at 1 , 3 , 6 , 9 , and 12 months . RESULTS Ninety-one women aged 48 to 73 years ( mean age 56.8 + /- 4.2 years ) participated in the study . The mean therapy duration was 8.8 + /- 3.8 years . No differences were noted between the two groups regarding age at menopause , body mass index , reasons to start therapy , hormone therapy duration , type of regimen , and reasons cited for hormone treatment discontinuation . After cessation of therapy , a similar percentage of patients in each group resumed hormone therapy . Climacteric syndromes , specifically vasomotor dysfunction , were more severe in group 1 than in group 2 during the first 3 months after hormone therapy withdrawal . However , by 6 months vasomotor symptoms were worse in group 2 . By 9 to 12 months , no difference was noted between groups . No differences were observed in the percentage of weight gain , vaginal bleeding , and atrophy after discontinuation of therapy by either method . CONCLUSIONS Our specific regimen of gradual discontinuation of hormone therapy merely postponed , and neither prevented nor minimized , the reappearance of vasomotor symptoms , mood deterioration , and sexual dysfunction , and the result ing discomfort Objective : The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy ( EPT ) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation . A secondary aim was to evaluate whether health-related quality of life ( HRQoL ) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT . Methods : Eighty-one postmenopausal women undergoing EPT because of hot flashes were r and omized to tapering down or abrupt discontinuation of EPT .  Vasomotor symptoms were recorded in self-registered diaries , and resumption of hormone therapy ( HT ) was asked for at every follow-up . The Psychological General Well-being Index was used to assess HRQoL. Results : Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up . About every other woman had resumed HT within 1 year . Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT . Conclusions : Women who initiate EPT  because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used , abrupt or taper down . Because , in addition to severity of flashes , decreased well-being was the main predictor of the risk to resume HT , it seems important to also discuss quality of life in parallel with efforts to discontinue HT Objective : To evaluate the effects of hormone therapy ( HT ) on cognition and subjective quality of life ( QoL ) in recently postmenopausal women with cognitive complaints . Methods : Cognitive Complaints in Early Menopause Trial ( COGENT ) was a r and omized , double-blind , placebo-controlled , multicenter , pilot study of 180 healthy postmenopausal women aged 45 to 55 years , r and omly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months . Outcome measures included memory , subjective cognition , QoL , sexuality , and sleep , which were assessed at baseline and month 4 . Results : The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women ’s Health Initiative . There were no differences between groups on any cognitive or QoL measures , except for an increase in sexual interest and thoughts with HT . Modest negative effects on short- and long-term verbal memory approached significance ( p < 0.10 ) . Women with baseline vasomotor symptoms ( VMS ) showed a decrease in VMS and an improvement in general QoL , but no cognitive benefit vs placebo . Conclusions : With the power to detect an effect size of ≥0.45 , this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women . GLOSSARY : BTA = Brief Test of Attention ; BVRT = Benton Visual Retention Test ; COGENT = Cognitive Complaints in Early Menopause Trial ; CRT = Educational Testing Service Card Rotation Test ; CVLT = California Verbal Learning ; FAS = Letter Fluency Test ; HERS = Heart and Estrogen/progestin Replacement Study ; HT = hormone therapy ; MFSQ = McCoy Female Sexuality Scale Question naire ; MFQ = The Memory Functioning Question naire ; PANAS = Positive and Negative Affect Scale ; PSQI = The Pittsburgh Sleep Quality Index ; QoL = subjective quality of life ; SWAN = Study of Women ’s Health Across the Nation ; UQoL = Utian Quality of Life ; VMS = vasomotor symptoms Test ; WHI = Women ’s Health Initiative ; WHISCA = WHI Study of Cognitive Aging ; WMS-R/DGT-F , MS-R/DGT-B = Digit Span Forward and Backward Subtests of the Wechsler Memory Scale – Revised BACKGROUND Evidence that long-term hormone therapy ( HT ) may increase the risk of serious adverse events led to a sharp reduction in all HT use , including short-term use for vasomotor symptom relief . We estimated women 's willingness to accept adverse event risks in exchange for vasomotor symptom relief when risks are communicated in absolute vs. relative terms . METHODS We developed a conjoint survey to elicit preferences across benefit and risk attributes of HT . The survey was administered via the Internet to 523 U.S. women aged 46 - 60 years . Participants evaluated pairs of hypothetical treatments and indicated preferences using a Likert-based scale . Risks were presented in absolute and relative terms . Satisfaction scores for HT risks and benefits were estimated using r and om-effects , ordered-probit regression . Maximum acceptable risk ( MAR ) was calculated as the increase in risk that reduces the satisfaction score for a given level of HT benefit to 0 . RESULTS For both risk versions , the least important attribute ( smallest difference in satisfaction scores ) was night sweat frequency ; heart attack risk was the most important ( largest difference in scores ) . Participants were more willing to accept risks in return for symptom relief when shown absolute vs. relative risks , although differences in MAR were statistically significant only for breast cancer risk . MARs for breast cancer and heart attack exceeded reported rates in most cases . CONCLUSIONS Many women may be willing to accept risks to control vasomotor symptoms . However , describing risks in different , but technically equivalent , ways affects women 's willingness to trade risks for benefits OBJECTIVE To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women . DESIGN In this double-blind , r and omized , placebo-controlled study , a total of 80 women ( mean age = 55.1 years ) , who reported 5 or more hot flush episodes per day , were r and omized to receive either 250 mg of st and ardized soy extract ( Glycine max AT ) a total of 100mg/day of isoflavone ( n = 40 ) or placebo ( n = 40 ) . Exclusion criteria included : contra-indication for hormone therapy ( HT ) , chronic gastrointestinal diseases , and users of HT within the preceding 6-months . For 10-months , climacteric symptoms were evaluated using a score card and the menopausal Kupperman index . Compliance and safety were also assessed . At baseline and the end of the study , lipid and hormonal profiles , as well as vaginal , mammographic and ultrasonographic parameters were measured . The t-test , Wilcoxon test and ANOVA were used in the statistical analysis . RESULTS At baseline , the mean number of hot flushes was 9.6 + /- 3.9 per day in the isoflavone group and 10.1+/-4.9 in the placebo group ( p>0.05 ) . After 10 months , there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo ( 3.1 + /- 2.3 and 5.9 + /- 4.3 , respectively ) ( p<0.001 ) . Kupperman index mean values showed a significant reduction in both groups . However , soy isoflavone was significantly superior to placebo , in reducing hot flush severity ( 69.9 % and 33.7 % , respectively ) ( p<0.001 ) . Endometrial thickness , mammography , vaginal cytology , lipids and hormonal profile did not change in both groups . No serious adverse event related to isoflavone treatment was reported . CONCLUSIONS The soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance , providing a safe and effective alternative therapeutic for postmenopausal women OBJECTIVE Hormone therapy ( HT ) has been suggested to improve vascular function and inflammation in menopausal women , although not consistently . We aim ed to investigate the effects of HT on endothelial function and inflammation , especially sCD40L , in early menopausal women , and the effect of common estrogen receptor ( ER ) polymorphisms on vascular responses to HT . STUDY DESIGN Eighty-four early menopausal women ( <3 years in menopause ) with menopausal complaints eligible for HT . Forty women received transdermal 17β-estradiol plus cyclical micronized progesterone for 3 months while 44 did not ( controls ) . MAIN OUTCOME MEASURES Brachial artery flow-mediated dilation ( FMD ) and vascular inflammation markers ( sICAM , sP-Selectin and sCD40L ) . Genetic polymorphisms of ERα ( PvuII 454 - 397T > C and XbaI 454 - 351A > G ) and ERβ ( AluI 1730A > G ) were also assessed . RESULTS The two groups did not differ at baseline . Following HT , vasomotor complaints ' severity , blood pressure , LDL , sCD40L , sICAM and sP-Selectin decreased and FMD increased compared to controls ( P<0.05 for all ) . ERβ AluI A allele presence was the most important independent predictor of  HT-induced increase in FMD while ERα XbaI A allele was the only independent predictor of decrease in sCD40L . CONCLUSIONS Short-term HT in early menopausal women improved endothelial function and inflammation . Specific ER polymorphisms that were found to be main determinants of HT-induced effects on endothelium could identify subgroups of women who may benefit the most from HT Context Caution about taking estrogen for treating  postmenopausal vasomotor symptoms has led to increasing substitution of herbal regimens despite few tests of their effectiveness . Contribution The authors r and omly assigned 351 perimenopausal or postmenopausal women to herbal treatments ( black cohosh , multibotanicals , or multibotanicals plus counseling about dietary soy ) , estrogen with or without progesterone , or placebo . At 3 , 6 , and 12 months , patients receiving the herbal interventions had the same change in vasomotor symptoms as those receiving placebo ( except for more severe symptoms at 12 months for patients taking multibotanicals plus dietary soy ) . Estrogen substantially decreased vasomotor symptoms . Caution s Most participants were white and were well-educated . Implication s Herbal regimens did not reduce postmenopausal vasomotor symptoms in this sample of women . The Editors Hormone therapy remains the recommended treatment for vasomotor symptoms , but trials have shown serious risks with even short-term use ( 1 , 2 ) . The use of herbs , particularly black cohosh , multibotanical supplements , and dietary soy for menopausal symptoms has grown dramatically ( 36 ) . Few of these approaches have been scientifically evaluated . Women and providers are seeking safe , effective alternatives to hormone therapy . We design ed the Herbal Alternatives for Menopause Trial ( HALT ) to provide rigorous evidence on the efficacy and short-term safety of commonly used naturopathic approaches for management of vasomotor symptoms . Methods Design Overview and Setting HALT was a 1-year double-blind , r and omized , controlled trial design ed to investigate the effects of 3 naturopathic approaches for  vasomotor symptom relief and hormone therapy compared with placebo . Study methods have been described elsewhere ( 7 ) . The Group Health Institutional Review Board approved this study , and a data and safety monitoring committee monitored it . The study was conducted at Group Health , an integrated health plan in Washington State . Participants Eligibility criteria were as follows : age 45 to 55 years ; late menopausal transition ( 1 skipped menses within the preceding 12 months ) or postmenopausal ( no bleeding within 12 months , or follicle-stimulating hormone level > 20 IU/mL if patient had undergone hysterectomy without bilateral oophorectomy ) ; and 2 or more vasomotor symptoms per day over 2 weeks ( 6 moderate to severe symptoms ) . Women in menopausal transition were included because many are highly symptomatic and trial data are lacking for this group . Exclusion criteria were the following : contraindications to hormone therapy ; use of hormone therapy or oral contraceptives within 3 months before the trial ; use of herbal medicines for menopausal symptoms within 1 month before the trial ; soy allergy ; bilateral oophorectomy ; history of breast cancer ; and nonadherence during the run-in period ( < 80 % of capsules taken ) . From May 2001 through August 2003 , women were recruited by using direct mail . Screening calls determined initial eligibility . Women attended an orientation visit at which eligibility was confirmed , physical measurements were collected , and placebo medication and question naires for the 2-week run-in period were provided . R and omization and Interventions Participants were r and omly assigned by using SAS software ( SAS Institute , Inc. , Cary , North Carolina ) , stratified by previous hormone therapy and hysterectomy ; block sizes within strata ranged from 5 to 25 . Treatment assignments were sent to the University of Washington Research Pharmacy , where medications were bottled and labeled with a sequential identification number without treatment group indication . At the r and omization visit , vasomotor symptom diaries and medication counts were examined to confirm eligibility and adherence . The study nurse determined the appropriate stratum , assigned the participant the next study number in that stratum without knowledge of group assignment , and distributed study medications . The publication of results from the Women 's Health Initiative ( WHI ) estrogenprogestin trial ( 2 ) raised new concerns about the safety of estrogen therapy . New study participants were given the choice of 5-arm ( including hormone therapy ) versus 4-arm ( no hormone therapy ) r and omization . Current participants gave consent again , incorporating risk estimates from the WHI , and were given the option of finding out whether they had been assigned to hormone therapy ; 16 were unblinded , 1 discontinued use of the study drug , and all remained enrolled . Following publication of the WHI Memory Study ( 8 , 9 ) , we informed participants of those findings and restricted r and omization to herbs and placebo . No further women were unblinded or discontinued use of the study drug . Naturopathic medicine provided the model for study interventions . The herbal products , doses , and soy diet were based on approaches used by naturopaths when the study was design ed ( 7 ) . The study groups were as follows : 1 ) black cohosh  ( Actaea racemosa or Cimicifuga racemosa , 160 mg daily ; 2.5 % triterpene glycosides ; 70 % ethanol extract ) ; 2 )  multibotanical ;  3 )  multibotanical plus soy diet counseling ; 4 ) conjugated equine estrogen , 0.625 mg daily , with ( for women with a uterus ) or without ( for women without a uterus ) medroxyprogesterone acetate , 2.5 mg ; and 5 ) placebo . The multibotanical delivered daily doses of the following : black cohosh , 200 mg ; alfalfa ( Medicago sativa ) , 400 mg ; boron , 4 mg ; chaste tree ( Vitex agnus-castus ) , 200 mg ; dong quai ( Angelica sinensis ) , 400 mg ; false unicorn ( Chamaelirium luteum ) , 200 mg ; licorice ( Glycyrrhiza glabra ) , 200 mg ; oats ( Avena sativa ) , 400 mg ; pomegranate ( Punica granatum ) , 400 mg ; Siberian ginseng ( Eleutherococcus senticosus , st and ardized constituents 0.8 % eleutherosides E and B ) , 400 mg . Black cohosh was provided by Pure World , Inc. , ( Hackensack , New Jersey ) . The multibotanical , ProGyne , was purchased from Progena Professional Formulations ( Albuquerque , New Mexico ) and encapsulated to study specifications . Both companies follow current good manufacturing practice s , and single batches were used . ConsumerLab.com ( White Plains , New York ) tested the products after the study commenced . Dong quai , false unicorn , and pomegranate were not detected , suggesting that they were of poor quality or did not contain the tested marker compounds . Other marker compounds were detected in the approximate doses as labeled ( 7 ) . The Appendix Table describes the herbal products in detail . Appendix Table . Consoli date d St and ards of Reporting Trials ( CONSORT ) Requirements for Controlled Trials of Herbal Interventions To facilitate blinding , medications and lactose placebo were encapsulated to provide 2 white and 2 blue capsules to each woman , and medication boxes were labeled with a unique identification number that did not indicate study group . The soy food intervention was modeled after a successful 5-a-day intervention ( 10 ) . We chose soy foods because of uncertainty about the efficacy of isoflavone supplements and because naturopaths commonly recommend whole soy foods . Participants received 5 telephone calls from a clinical dietitian and a 34-page booklet recommending 2 soy food servings per day ( 12 to 20 g of soy protein ) ( 7 ) . Other participants received 1 telephone call and a similar booklet reinforcing fruit and vegetable intake . Participants were instructed not to discuss dietitian calls with study nurses and were unaware that soy counseling was linked to the multibotanical . Outcomes and Measurements The primary outcomes were change from baseline ( measured over 2-week run-in period ) to 3 , 6 , and 12 months ( each measured for 4 weeks ) and change from baseline to the average for all follow-ups with regard to the mean frequency and intensity of vasomotor symptoms ( daytime hot flashes plus night sweats ) and the mean Wiklund Vasomotor Symptom Subscale score ( 11 , 12 ) . We also evaluated change from baseline to follow-up ( months 3 , 6 , and 12 and average change ) for daytime hot flash rate , night sweat rate , and the total Wiklund Menopause Symptom Scale score . Symptom diaries and global ratings of menopause symptoms are almost universally used in studies of vasomotor symptoms . Participants used a  vasomotor symptom diary  to record daytime hot flashes and night sweats , rating intensity as mild , moderate , or severe ( scale , 1 to 3 ) , as recommended by the U.S. Food and Drug Administration ( 13 ) . Women completed the Wiklund Menopause Symptom Scale , rating the severity of 13 menopausal symptoms ( sweats , hot flashes , sleep disturbance , fatigue , vaginal dryness , depression , headache , irritability , muscle/joint pain , breast tenderness , nervousness , palpitations , and dizziness/fainting on a scale of 0 ( none ) to 10 ( severe ) ( 11 ) . Soy food intake was monitored by using a self-reported , vali date d soy food question naire ( 14 ) . Follow-up Procedures Participants returned to the research clinic at 3 , 6 , and 12 months . Question naires were collected , and study medication was dispensed . Medication adherence counts were conducted by staff without participant contact and without knowledge of treatment assignment . Study nurses encouraged adherence and monitored adverse events during monthly telephone calls and at visits . Adverse events were identified through participants ' responses to the question , Have you had any medical problems or been hospitalized ? Responses were recorded and adverse events were followed until they were resolved . The study nurse determined intensity ( mild , moderate , or severe ) and whether the event was serious ( yes or no ) . Events were review ed by the study physician , who determined whether the event was study related , without knowledge of group assignment . Adverse events were coded by using the Coding Symbols for Thesaurus of Adverse Reaction Terms ( 15 ) . The Data and Safety Monitoring Committee review ed study progress and unblinded outcome and safety data 5 times . Statistical Analysis The study was powered to detect an effect of Objective : To determine the safety and efficacy of an oral soy isoflavone extract for relief of  menopausal hot flushes . Design : This was a double‐blind , r and omized , parallel group , outpatient , multicenter ( 15 sites ) study . A total of 177 postmenopausal women ( mean age = 55 years ) who were experiencing five or more hot flushes per day were r and omized to receive either soy isoflavone extract ( total of 50 mg genistin and daidzin per day ) or placebo . Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion . Body weight , symptoms , and safety were evaluated at all visits . Results : Relief of vasomotor symptoms was observed in both groups . Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group , whereas the placebo group experienced no relief for the first 4 weeks . Differences between evaluable subjects in both groups were statistically significant over 6 weeks ( p = 0.03 ) . Over 12 weeks , between‐group differences approached significance ( p = 0.08 ) . Endometrial thickness evaluated by ultrasound , lipoproteins , bone markers , sex hormone‐binding globulin and follicle‐stimulating hormone , and vaginal cytology did not change in either group . Conclusions : Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium . Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes . ( Menopause 2000;7:236‐242 . © 2000 , The North American Menopause Society . Objectives : To examine the association between hormone therapy ( HT ) and cognitive performance or dementia , focusing on the duration and type of treatment used , as well as the timing of initiation of HT in relation to the menopause . Methods : Women 65 years and older were recruited in France as part of the Three City Study . At baseline and 2- and 4-year follow-up , women were administered a short cognitive test battery and a clinical diagnosis of dementia was made . Detailed information was also gathered relating to current and past HT use . Analysis was adjusted for a number of sociodemographic , behavioral , physical , and mental health variables , as well as APOE ε4 . Results : Among 3,130 naturally postmenopausal women , current HT users performed significantly better than never users  on verbal fluency , working memory , and psychomotor speed . These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial . However , initiation of HT close to the menopause was not associated with better cognition . HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE ε4 . Conclusions : Current hormone therapy ( HT ) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used . We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life . Current HT may decrease the risk of dementia associated with the APOE ε4 allele PURPOSE Vasomotor symptoms are common adverse effects of antiestrogen hormone treatment in conventional breast cancer care . Hormone replacement therapy is contraindicated in patients with breast cancer .  Venlafaxine ( Effexor ) , the therapy of choice for these symptoms , has numerous adverse effects . Recent studies suggest acupuncture may be effective in reducing vasomotor symptoms in menopausal women . This r and omized controlled trial tested whether acupuncture reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine . PATIENTS AND METHODS Fifty patients were r and omly assigned to receive 12 weeks of acupuncture ( n = 25 ) or venlafaxine ( n = 25 ) treatment . Health outcomes were measured for up to 1 year post-treatment . RESULTS Both groups exhibited significant decreases in hot flashes , depressive symptoms , and other quality -of-life symptoms , including significant improvements in mental health from pre- to post-treatment . These changes were similar in both groups , indicating that acupuncture was as effective as venlafaxine . By 2 weeks post-treatment , the venlafaxine group experienced significant increases in hot flashes , whereas hot flashes in the acupuncture group remained at low levels . The venlafaxine group experienced 18 incidences of adverse effects ( eg , nausea , dry mouth , dizziness , anxiety ) , whereas the acupuncture group experienced no negative adverse effects . Acupuncture had the additional benefit of increased sex drive in some women , and most reported an improvement in their energy , clarity of thought , and sense of well-being . CONCLUSION Acupuncture appears to be equivalent to drug therapy in these patients . It is a safe , effective and durable treatment for vasomotor symptoms secondary to long-term antiestrogen hormone use in patients with breast cancer BACKGROUND To evaluate the differences between the immediate and tapered cessation protocol s of hormone therapy in terms of recurrence of menopausal symptoms . MATERIAL S AND METHODS In this prospect i ve , r and omized clinical study 70 consecutive patients in whom hormone therapy was no longer preferred were recruited from the menopause clinic of a university hospital and rank r and omized into two groups . In group 1 ( n=35 ) hormone therapy was immediately discontinued and in group 2 ( n=35 ) the medication was tapered . Every patient was question ed about vasomotor symptoms before the initiation of hormone therapy at the first visit , and then revisited at the end of 2 and 4 weeks . RESULTS We did not find any statistically significant difference between two protocol s in terms of symptom severity and frequency at the end of 2 and 4 weeks of discontinuation . Although statistically insignificant , the symptoms tended to recur in fewer patients and in a less severe form in both groups when compared with their pretreatment status . CONCLUSIONS Tapering or immediate discontinuing of hormone therapy did not affect the recurrence rate and severity of menopausal symptoms at the end of 4 weeks Background : Hormone therapy ( HT ) is the treatment of choice for the alleviation of menopausal symptoms ; concerns , however , about its concomitant long-term health risks have limited its use . DT56a is a unique enzymatic isolate of soybeans . The purpose of our study was to evaluate the efficacy and safety of DT56a , compared to HT , in symptomatic post-menopausal women . Subjects and methods : Eighty-nine post-menopausal women were studied prospect ively . Women with climacteric symptoms were r and omly assigned to receive eitherDT56a ( no.=27 ) or oral low dose continuous combined HT ( no.=26 ) . Symptomatic women not wishing to receive any treatment served as controls ( no.=36 ) . Menopausal symptoms as assessed through the Kupperman index , serum lipids and lipoproteins , calcium , as well as bone mineral density ( BMD ) , endometrial thickness , and mammography were assessed at baseline and at 12 months . Results : Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms ( mean difference in Kupperman score , DT56a group : −3.98 , HT group −5.601 , no treatment group + 1.76 , p-value < 0.001 ) . Lumbar spine BMD T-score was significantly lower in women receiving no treatment , as opposed to the two treatment arms which showed no significant change ( No treatment , baseline : −0.60 , final : −0.85 , p=0.001 ; HT , baseline : −84 , final −0.99 , p=0.79 ; DT56a , baseline −0.51 , final : −0.76 , p=0.75 ) . No differences in femoral bone density , ET or mammography classification were detected in any of the treatment arms . Likewise , serum lipids or lipoproteins did not differ between the three groups . Conclusions : DT56a decreased menopausal symptoms significantly and in the same degree as HT OBJECTIVE To investigate somatic symptom relief , gonadotropin secretion , and endogenous and rogen bioavailability ( protein-bound and free ) during 3 months of estrogen- and rogen therapy or matched estrogen-only replacement therapy . DESIGN Ninety-three naturally menopausal out patients with 6 or more months of amenorrhea , who were experiencing mild-to-moderate vasomotor symptoms , were r and omized to receive one of five treatments : oral esterified estrogens ( 0.625 mg or 1.25 mg ) , oral esterified estrogens combined with methyltestosterone ( 0.625 mg combined with 1.25 mg methyltestosterone or esterified estrogens 1.25 mg combined with 2.5 mg methyltestosterone ) , or placebo for 12 weeks . All treatments were preceded by a 4-week placebo lead-in period . RESULTS Patients receiving the lower dose of estrogen- and rogen therapy had fewer somatic menopausal symptoms than patients receiving the lower dose estrogen ( 0.625 mg ) , and they experienced somatic symptom relief similar to those patients receiving the higher dose of estrogen ( 1.25 mg ) . Significantly greater luteinizing hormone suppression ( p < or = 0.03 ) occurred in estrogen- and rogen groups compared to estrogen groups , suggesting that added and rogen might mediate a more pronounced negative feedback on the hypothalamic-pituitary axis . Sex hormone-binding globulin increased significantly in both estrogen-treated groups ( p < or = 0.01 ) , whereas decreases occurred in both estrogen- and rogen groups ( p < or = 0.006 ) . The higher dose estrogen-only preparation significantly reduced and rostenedione ( p < or = 0.01 ) and dehydroepi and rosterone sulfate ( p < or = 0.005 ) . CONCLUSION The extent of relief with lower dose estrogen- and rogen therapy was similar to higher dose estrogen-only treatment . The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen- and rogen therapy on luteinizing hormone secretion . The marked differences in circulating levels of sex hormone building globulin , which were increased by estrogen and decreased by estrogen- and rogen , and the result ing impact on bioavailable and rogens and estrogens could also explain the differential somatic relief with both treatments . Endogenous adrenal and rogens were lower in women treated with esterified estrogens 1.25 mg/day , suggesting that estrogen therapy can produce a significant hypo and rogenic state by inhibiting production or accelerating clearance of adrenal and rogens Objective To evaluate the effects of electro-acupuncture ( EA ) and hormone therapy ( HT ) on vasomotor symptoms in women with a history of breast cancer . Methods Forty-five women were r and omized to EA  ( n = 27 ) for 12 weeks or HT ( n = 18 ) for 24 months . The number of and distress caused by hot flushes were registered daily before , during and up to 24 months after start of treatment . Results In 19 women who completed 12 weeks of EA , the median number of hot flushes/24 h decreased from 9.6 ( interquartile range ( IQR ) 6.6–9.9 ) at baseline to 4.3 ( IQR 1.0–7.1 ) at 12 weeks of treatment ( p < 0.001 ) . At 12 months after start of treatment , 14 women with only the initial 12 weeks of EA had a median number of flushes/24 h of 4.9 ( IQR 1.8–7.3 ) , and at 24 months seven women with no other treatment than EA had 2.1 ( IQR 1.6–2.8 ) flushes/24 h. Another five women had a decreased number of flushes after having additional EA . The 18 women with HT had a baseline median number of flushes/24 h of 6.6 ( IQR 4.0–8.9 ) , and 0.0 ( IQR 0.0–1.6 ; p = 0.001 ) at 12 weeks . Conclusion Electro-acupuncture is a possible treatment of vasomotor symptoms for women with breast cancer and should be further studied for this group of women 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 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 OBJECTIVES A population -based study was used to describe healthcare seeking behavior for  menopausal  symptoms and treatment among women 40 - 65 years old in the United States . METHODS Participants were recruited into the Menopause Epidemiology Study from the KnowledgePanel(SM ) , which is selected by r and om digit dialing and probability sampling from the US population . From this source , 6201 women 40 - 65 years old were contacted and 4402 women participated . From the 3135 peri- and postmenopausal women , detailed information was obtained on menopausal symptoms , healthcare seeking , medication usage , and symptom relief from the medication . RESULTS Many women ( 60 % ) reported seeking health care for their menopausal symptoms . More than half of these women sought health care in the past 12 months . Vasomotor symptoms were the most frequently reported menopause symptoms across all races/ethnicities , and the most common symptoms discussed with a health care professional . One-third of the women ( 34 % ) used only hormone therapies , 12 % used complementary and /or alternative medicines , and 16 % used both for treatment of menopausal symptoms . CONCLUSIONS This study has shown that a large number of women consult healthcare providers for menopausal symptoms , indicating these symptoms are bothersome . Yet , in the United States , there is considerable variation in the symptomatology , healthcare seeking , and use of therapies for menopausal symptoms across cultures . To alleviate these symptoms women have tried alternative treatments as well as hormone therapies , yet many women did not get complete relief of specific symptoms Deciding about hormone therapy ( HT ) use is particularly complex for women with mobility impairments . While HT controls menopausal symptoms , the potential increased risk of blood clots result ing from physical inactivity can contraindicate HT use . These women , therefore , may benefit from interventions to help them tailor st and ard information about HT . We r and omly assigned women to receive either a tailored decision support intervention or st and ard menopausal information . Both groups ( n = 176 ) significantly decreased their decisional conflict and uncertainty and increased knowledge after receiving the treatment material s. We interpret the findings in the context of limited medical information about HT for women with disabilities Objective This study aims to present methods and baseline data from the Early versus Late Intervention Trial with Estradiol ( ELITE ) , the only clinical trial design ed to specifically test the timing hypothesis of postmenopausal hormone therapy ( HT ) . The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time since menopause . Methods ELITE is a r and omized , double-blind , placebo-controlled trial with a 2 × 2 factorial design . Six hundred forty-three healthy postmenopausal women without cardiovascular disease were r and omized to oral estradiol or placebo for up to 6 to 7 years according to time since menopause ( < 6 or ≥10 y ) . Carotid artery intima-media thickness ( CIMT ) and cardiac computed tomography  were conducted to determine HT effects on sub clinical atherosclerosis across menopause strata . Results Participants in the early and late postmenopausal strata were well-separated by mean age ( 55.4 vs 65.4 y ) and median time since menopause ( 3.5 vs 14.3 y ) . Expected risk factors ( age , blood pressure , and body mass index ) were associated with CIMT at baseline in both strata . In the early postmenopausal group , but not in the late postmenopausal group , we observed significant associations between CIMT and factors that may play a role in the responsiveness of atherosclerosis progression according to timing of HT initiation . These include low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , sex hormone – binding globulin , and serum total estradiol . Conclusions The ELITE r and omized controlled trial is timely and unique . Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease OBJECTIVES Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life ( QOL ) . The aims of this study were to measure menopausal symptoms , mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators . METHODS A prospect i ve , r and omized , placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms , anxiety and depressive symptoms , and QOL in 152 postmenopausal women over a 12 month study period .  Menopausal symptoms were measured using a modified Kupperman 's scale . Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life question naire , respectively . RESULTS Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high . Over 12 months , after adjustment for differences in baseline scoring , there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group . There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo . CONCLUSIONS These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood . In addition , the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians . Therefore , when considering the reasons for prescribing hormone replacement therapy in this population , protection against osteoporosis will for most women be the prime consideration OBJECTIVE To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy ( HRT ) . METHODS This prospect i ve , double-blind and placebo-controlled study included 50 postmenopausal women r and omly divided into two groups : 25 women on soy germ isoflavones ( 60 mg per day , capsules ) and 25 women on placebo .  Inclusion criteria included : non-vegetarian , non-asian women whose last menstruation date d at least 12 months prior to the beginning of the study , with FSH > 40 mIU/ml , hot flushes and contraindication for HRT , not using tamoxifen or antibiotic and no disease of the gastrointestinal tract . For 6 months , the Kupperman menopausal index ( KMI ) , the vaginal cytological maturation value ( MV ) and both hormonal and lipid profiles were assessed . The t-test and analysis of variance ( ANOVA ) were employed to compare the two groups . RESULTS In both groups , a decreased KI rate was observed . However , isoflavone was significantly superior to placebo in reducing hot flushes ( 44 % versus 10 % , respectively ) ( P < 0.05 ) . After 6 months , the isoflavone group showed increased estradiol levels with unchanged FSH , LH , and vaginal cytology , and a reduction of 11.8 % in LDL and an increase of 27.3 % in HDL ( P < 0.05 ) . In the placebo group , just a reduction in MV was observed after 6 months ( P < 0.05 ) . CONCLUSIONS Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile , showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT BACKGROUND Hormone replacement therapy ( HT ) is known to increase the risk of breast cancer in healthy women , but its effect on breast cancer risk in breast cancer survivors is less clear . The r and omized HABITS study , which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer , was stopped early due to suspicions of an increased risk of new breast cancer events following HT . We present results after extended follow-up . METHODS HABITS was a r and omized , non-placebo-controlled noninferiority trial that aim ed to be at a power of 80 % to detect a 36 % increase in the hazard ratio ( HR ) for a new breast cancer event following HT . Cox models were used to estimate relative risks of a breast cancer event , the maximum likelihood method was used to calculate 95 % confidence intervals ( CIs ) , and chi(2 ) tests were used to assess statistical significance , with all P values based on two-sided tests . The absolute risk of a new breast cancer event was estimated with the cumulative incidence function . Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone . RESULTS Of the 447 women r and omly assigned , 442 could be followed for a median of 4 years . Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event ( HR = 2.4 , 95 % CI = 1.3 to 4.2 ) . Cumulative incidences at 5 years were 22.2 % in the HT arm and 8.0 % in the control arm . By the end of follow-up , six women in the HT arm had died of breast cancer and six were alive with distant metastases . In the control arm , five women had died of breast cancer and four had metastatic breast cancer ( P = .51 , log-rank test ) . CONCLUSION After extended follow-up , there was a clinical ly and statistically significant increased risk of a new breast cancer event in survivors who took HT 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 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 This study compared the effects of a continuous-combined regimen of low-dose hormone therapy ( LD-HT ) versus tibolone and supplemental calcium/vitamin D3 ( control ) on quality of life ( QoL ) in symptomatic postmenopausal women . DESIGN This study was a prospect i ve , r and omised , double-blind , comparative trial with a control group . SETTING The study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora , Brazil . POPULATION A total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited . These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy . INTERVENTIONS The patients were r and omised into three groups : ( 1 ) daily treatment with 2.5 mg tibolone ( n=64 ) , ( 2 ) 50 mg calcium carbonate+200 IU vitamin D3 ( Ca/Vit D3 , n=54 ) or ( 3 ) 1 mg oestradiol+0.5 mg norethindrone acetate ( E2/NETA , n=56 ) for 12 weeks . PRIMARY OUTCOME MEASURES The primary outcome was the evaluation of QoL using the Women 's Health Question naire ( WHQ ) in all subjects at baseline and after 4 , 8 and 12 weeks of treatment . RESULTS A total of 130 women in the following groups completed the study : tibolone ( n=42 ) , Ca/Vit D3 ( n=44 ) and E2/NETA ( n=44 ) . An improved QoL based on the WHQ was observed at T0 ( 80.12±14.04 , 77.73±15.3 , 77.45±15.4 ) and T12 ( 57.0±15.5 , 55.7±16.7 , 58.4±12.6 ) for the tibolone , E2+NETA and Ca/Vit D3 groups , respectively ( p values < 0.05 ) . The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms . The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups ( 4.2±26 , 5.6±2.8 , 5.4±2.8 , respectively , p values < 0.05 ) . LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms ( 3.2±1.5 , 4.0±1.8 , 4.3±2.0 , respectively , p values < 0.05 ) . Adverse effects were few and mild . CONCLUSIONS An improved QoL was observed in the three study groups . Tibolone primarily improved sexual function , and E2/NETA exhibited a superior response for vasomotor symptoms The purpose of this study was to determine whether psychological support associated with  hormone replacement therapy ( HRT )  was more beneficial than replacement therapy alone . Our findings showed that HRT alone was more effective against vasomotor symptoms than HRT with psychological treatment ( PT ) . While the combination of both treatment modalities ( HRT + PT ) was more effective against insomnia , nervousness , melancholy , fatigue , palpitations , and vertigo .  Hormonal treatment alone and HRT with psychological treatment had little effect against paresthesia or tingling . Neither HRT alone nor HRT with psychological treatment was effective against joint and muscle pain or headache OBJECTIVE To compare relief of vasomotor symptoms , changes in lipoproteins , and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy ( HRT ) of estradiol valerate and norethisterone or tibolone 2.5 mg/day . METHODS In a multicenter , r and omized , open-label study , 235 postmenopausal women received one of the above-mentioned treatments . Fasting lipoproteins were measured at baseline and at 3 , 6 , and 12 months . At each visit , participants completed Greene climacteric question naires and recorded any bleeding episodes . Data are presented as mean + /- st and ard deviation if normally distributed , median and interquartile range if non-normally distributed , or as frequency count . For menopausal symptoms and diary card data , the differences were tested by Wilcoxon rank-sum test . RESULTS One hundred sixteen women received continuous  combined HRT and 119 women received  tibolone ; 72 and 76 women , respectively , completed 12 months of therapy . Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol . Continuous combined HRT , but not tibolone , significantly reduced low-density lipoprotein levels . Both treatments reduced high-density lipoprotein levels , but the effect was more profound with tibolone . The initial bleeding score was higher for women taking continuous combined HRT ; however , by the end of the study , the percentages of amenorrheal women were comparable . Endometrial histology was similar for both treatments at the end of the study , although two cases of proliferative endometrium were found in the tibolone group . CONCLUSION Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile Objective To evaluate the efficacy and safety of Heyan Kuntai Capsule ( 和颜坤泰胶囊 , HYKT ) and hormone therapy ( HT ) on perimenopausal syndromes ( PMSs ) . Methods From 2005 to 2008 , 390 women with PMSs were recruited from 4 clinic centers . The inclusion criteria included ages 40 to 60 years , estradiol ( E2 ) below 30 ng/L , and follicle stimulating hormone ( FSH ) above 40 IU/L , etc . The patients were r and omly assigned to HYKT group or HT group by r and om number table method , administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months . During treatment , the patients were interviewed quarterly , Kupperman Menopausal Index ( KMI ) scores , hot flush scores , insomnia scores , Menopause-Specific Quality of Life ( MENQOL ) scores and adverse effects were used for evaluating drug efficacy and safety respectively . The last interview was made at the end of 12-month treatment Results After treatment , KMI scores of HYKT group and HT group were both significantly decreased compared with baseline ( P < 0.01 ) and there was no significant difference between groups ( P > 0.05 ) , except that KMI of HYKT group was higher after 3-month treatment ( P < 0.05 ) . After treatment , hot flush and insomnia scores were both improved significantly in two groups ( P < 0.01 ) ; and HT had a better performance than HYKT in improving hot flush ( P < 0.05 ) . MENQOL were significantly improved in both groups after treatment ( P < 0.01 ) ; but there was no significant difference between two groups ( P > 0.05 ) . The incidence of adverse event in the HYKT group was much lower than that in the HT group ( P < 0.01 ) . Conclusions HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions . Although HYKT exerted curative effects more slowly than hormone , it possessed better safety profile than hormone The postmenopausal hormone therapy ( PHT ) component of the Women ’s Health Initiative ( WHI ) is composed of two r and omized , placebo-controlled , double-blind trials in postmenopausal women aged 50 to 79 years at initial screening , testing the effects of estrogen alone ( E-alone ) and estrogen plus progestin ( E P ) on coronary heart disease ( CHD ) as the primary outcome , hip and other fractures and colorectal cancer as secondary outcomes , and pulmonary embolism , breast and endometrial cancers as potential risks . The design and rationale of the PHT trials , including general eligibility and exclusion criteria and considerations regarding sample size and statistical power , have been described previously ( 1 ) . Postmenopausal hormones have been initiated in menopausal women for the treatment of vasomotor symptoms , mood disturbances , vaginal dryness , and prevention of rapid bone loss for several decades . Despite a paucity of data on effects of initiating hormone use in older women , postmenopausal hormones have also been promoted for the prevention of CHD , osteoporotic fractures , and other diseases that occur years after menopause ( 2 ) . It is generally recommended ( 2 ) that women with a uterus be prescribed a combination of estrogen and progestin to prevent Objectives : Observational studies suggest reduced risk of Alzheimer disease ( AD ) in users of hormone therapy ( HT )  , but trials show higher risk . We examined whether the association of HT with AD varies with timing or type of HT use . Methods : Between 1995 and 2006 , the population -based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT .  During this interval , 176 women developed incident AD . Cox proportional hazard models evaluated the association of HT use with AD , overall and in relation to timing , duration of use , and type ( opposed vs unopposed ) of HT . Results : Women who used any type of HT within 5 years of menopause had 30 % less risk of AD ( 95 % confidence interval 0.49–0.99 ) , especially if use was for 10 or more years . By contrast , AD risk was not reduced among those who had initiated HT 5 or more years after menopause . Instead , rates were increased among those who began “ opposed ” estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline ( adjusted hazard ratio 1.93 ; 95 % confidence interval 0.94–3.96 ) . This last hazard ratio was similar to the ratio of 2.05 reported in r and omized trial participants assigned to opposed HT . Conclusions : Association of HT use and risk of AD may depend on timing of use . Although possibly beneficial if taken during a critical window near menopause , HT ( especially opposed compounds ) initiated in later life may be associated with increased risk . The relation of AD risk to timing and type of HT deserves further study OBJECTIVE Decision-making at menopause remains a challenge for women and their health care providers as the paradigm for hormone therapy continues to evolve . The role of decision-support for this process remains to be defined . METHODS A r and omized controlled trial of a computer-based hormone therapy ( HT ) decision-aid versus a control intervention consisting of a printed pamphlet among 177 post-menopausal women receiving care in a Veterans Affairs Medical Center . RESULTS Participants found the computer-based decision-aid  easy to use and retained risk information incorporated from emerging scientific data . There was no difference between groups with respect to the primary outcomes of knowledge , satisfaction with decision , decisional conflict or HT use . A trend was reported towards decreased decisional conflict in the evidence in decision-making ( p=0.07 ) and factors of uncertainty ( p=0.06 ) domains among the subset of participants who were on HT at baseline and used the computer-based decision-aid . CONCLUSION The computer-based decision-aid was able to effectively incorporate emerging scientific information but was no more effective than a printed pamphlet control with regard to improving decision-process outcomes . PRACTICE IMPLICATION S The incremental benefit of a complex versus simpler decision-aid for post-menopausal women remains to be established prior to widespread dissemination of interactive computer-based HT decision-aids OBJECTIVES To describe Australian-born women 's experience of symptoms during the natural menopause transition and the relative contribution of menopausal and health status , social factors and lifestyle behaviours . DESIGN A community based cross-sectional survey by telephone interview was carried out on a r and omly derived sample of Melbourne women . PARTICIPANTS The participants were 2000 Australian-born women , aged between 45 and 55 years . OUTCOME MEASURES A list of 22 symptoms was used . Explanatory variables were : sociodemographic variables ; menopausal and health status ; lifestyle behaviours ; attitudes to ageing and to menopause . RESULTS A 70 % response rate was achieved for eligible women who could be contacted during the study . Premenopausal women were the least symptomatic and perimenopausal women the most symptomatic . Factor analysis found seven common factors from the 22 symptoms studied . Menopausal status based on menstrual history was significantly related to two groups of symptoms : vasomotor symptoms , which increased through the menopausal transition ; and general somatic symptoms which were more frequent in the perimenopause . Analysis of variance of factor scores found fewer symptoms with increasing years of education , better self-rated health , the use of fewer non-prescription medications , the absence of chronic health conditions , a low level of interpersonal stress , the absence of premenstrual complaints , not currently smoking , exercise at least once a week , and positive attitudes to ageing and menopause . CONCLUSIONS Many factors unrelated to hormonal changes contributed to the symptoms . Longitudinal investigation is needed to determine the relative importance of hormonal , psychosocial and lifestyle variables in the aetiology of mid-life symptoms OBJECTIVES To compare the effects of daily ingestion of dietary soy supplementation , low-dose hormone therapy ( HT ) and placebo on psychological , somatic and urogenital symptoms in postmenopausal women . STUDY DESIGN A double-blind , r and omized , controlled trial . Sixty healthy , symptomatic , postmenopausal women of 40 - 60 years of age were allocated to use dietary soy supplementation ( containing 90 mg of isoflavone ) or HT ( 1 mg estradiol and 0.5 mg norethisterone acetate ) or placebo . MAIN OUTCOME MEASURES the Menopause Rating Scale ( MRS ) was used to assess menopausal symptoms at baseline and after 16 weeks of treatment . Intention-to-treat analyses were performed using the chi-square test , Fisher 's exact test , the Kruskal-Wallis non-parametric test and analysis of variance ( ANOVA ) . RESULTS No statistically significant differences were found between the groups with respect to baseline clinical and sociodemographic characteristics . The psychological , somatic and urogenital symptoms analyzed in the MRS improved during treatment in all the groups , except for urogenital symptoms in the placebo group in which no significant changes were detected . Comparison between groups revealed a statistically significant improvement in somatic symptoms ( hot flashes and muscle pain ) in the users of HT ( -45.6 % ) and dietary soy supplementation ( -49.8 % ) . Urogenital symptoms ( vaginal dryness ) improved significantly in HT users ( -38.6 % ) and in users of the dietary soy supplementation ( -31.2 % ) . There was no statistically significant difference between the groups with respect to overall MRS score or to scores obtained in the psychological symptoms subscale . CONCLUSION Dietary soy supplementation may constitute an effective alternative therapy for somatic and urogenital symptoms of the menopause AIMS The use of hormone therapy ( HT ) is a relevant and topical issue in the treatment of menopausal symptoms in women . Information regarding the effects of combination treatment with estrogen and progesterone as well as treatment timing on cognitive function is lacking and was evaluated in healthy pre- and postmenopausal women . METHODS Sixteen premenopausal ( 45 - 51 years ) and 16 postmenopausal ( 58 - 70 years ) women were r and omly assigned to receive either estrogen + progestin therapy ( HT ) or placebo ( PL ) for six months . The study was double-blind . Cognitive performance was measured at baseline and follow up with tests of verbal and visuomotor functions , verbal and visual memory , and attention . RESULTS In premenopausal women , cognitive attention , when compared to baseline , improved with HT but declined slightly with PL in the two-choice reaction time task ( P = 0.049 ) , while PL was associated with better performance in tests of shared attention ( P = 0.024 ) and auditory attention ( P < 0.05 ) . In postmenopausal women , HT was associated with improved performance in verbal episodic memory ( P = 0.024 ) and a minor decline in auditory attention ( P = 0.025 ) . CONCLUSIONS HT , with estradiol valerate and norethisterone , in healthy women showed only minor effects on attention around the menopausal transition and on memory in postmenopause Background The aim of the study was to determine the effect of postmenopausal hormone therapy on women 's symptom reporting and quality of life in a r and omized trial . Methods 1823 women participated in the Estonian Postmenopausal Hormone Therapy ( EPHT ) Trial between 1999 and 2004 . Women were r and omized to open-label continuous combined hormone therapy or no treatment , or to blind hormone therapy or placebo . The average follow-up period was 3.6 years . Prevalence of symptoms and quality of life according to EQ-5D were assessed by annually mailed question naires . Results In the hormone therapy arms , less women reported hot flushes ( OR 0.20 ; 95 % CI : 0.14–0.28 ) , sweating ( OR 0.56 ; 95 % CI : 0.44–0.72 ) , and sleeping problems ( OR 0.66 ; 95 % CI : 0.52–0.84 ) , but more women reported episodes of vaginal bleeding ( OR 19.65 ; 95 % CI : 12.15–31.79 ) . There was no difference between the trial arms in the prevalence of other symptoms over time . Quality of life did not depend on hormone therapy use . Conclusion Postmenopausal hormone therapy decreased vasomotor symptoms and sleeping problems , but increased episodes of vaginal bleeding , and had no effect on quality of life . Trial registration numberIS RCT Clinical trials indicate that hormone therapy ( HT ) does not decrease cardiovascular disease events or angiographic coronary disease progression . The effects of HT on SVG vessels are unknown . To determine whether postmenopausal hormone therapy started after coronary bypass surgery ( CABG ) decreases saphenous vein graft ( SVG ) disease , we conducted a multicenter r and omized placebo-controlled angiographic study of estradiol+/-medroxyprogesterone started within 6 months of CABG in 83 postmenopausal women .  Angiographic and intravascular ultrasound ( IVUS ) assessment at 6 and 42 months was planned to assess SVG disease progression . The study was stopped early following publication of the Women 's Health Initiative Estrogen/Progestin study . Eighty-three subjects underwent a 6-month angiogram with 63 undergoing IVUS . Forty-five subjects completed the 42-month  angiogram  ( 20 underwent 42-month IVUS ) . In analysis of paired 6- and 42-month angiogram and IVUS studies , HT slowed angiographic progression of SVG disease assessed by mean percent stenosis ( p<0.001 ) , minimal lumen diameter ( p=0.029 ) , and total plaque volume ( p=0.006 ) . In contrast , HT accelerated disease progression in non-bypassed native coronary arteries ( minimum lumen diameter , p=0.01 ) . SVG disease and closure occurred in 38 % subjects within 1-year post-CABG . The groups had similar frequency of cardiovascular events expect for angioplasty that occurred in eight HT compared to one placebo subject ( p<0.05 ) . In HT subjects angioplasty was indicated for native coronary arterial stenoses while in the placebo subject angioplasty was indicated for SVG stenosis . This study suggests that hormone treatment may slow SVG disease progression while accelerating atherosclerosis in non-bypassed native coronary arteries BACKGROUND Menopausal symptoms can affect women 's health and wellbeing . It is important to develop interventions to alleviate symptoms , especially given recent evidence result ing in many women no longer choosing to take hormone replacement therapy . Exercise may prove useful in alleviating symptoms , although evidence on its effectiveness has been conflicting . AIM To examine the association between exercise participation , body mass index ( BMI ) , and health-related quality of life in women of menopausal-age . DESIGN OF STUDY Survey of women of menopausal age . SETTING West Midl and s , Engl and . METHOD Women aged 46 - 55 years ( n = 2399 ) registered with six general practice s in the West Midl and s were sent a question naire containing items relating to demographics , lifestyle factors , weight , height , exercise participation , menopausal bleeding patterns , and health-related quality of life ( including vasomotor symptoms ) . RESULTS One thous and two hundred and six ( 50.3 % ) women replied . Women who were regularly active reported better health-related quality of life scores than women who were not regularly active ( P<0.01 for all significant subscales ) . No difference in vasomotor symptoms was recorded for exercise status . Women who were obese reported significantly higher vasomotor symptom scores than women of normal weight ( P<0.01 ) . Women who were obese reported significantly higher somatic symptoms ( P<0.001 ) and attractiveness concern scores ( P<0.001 ) than women of normal weight or those who were overweight . CONCLUSION The data suggest a positive association between somatic and psychological dimensions of health-related quality of life and participation in regular exercise .  Women with BMI scores in the normal range reported lower vasomotor symptom scores and better health-related quality of life scores than heavier women . Further evidence from high- quality r and omised controlled trials is required to assess whether exercise interventions are effective for management of menopausal symptoms Objective . Continuous combined hormone replacement therapy ( ccHRT ) based on estradiol valerate ( E2V ) and medroxyprogesterone acetate ( MPA ) is effective for relief of menopausal symptoms three years or more after the menopause . This study was undertaken to examine the efficacy and tolerability of ccHRT in early postmenopausal women ( last menstrual period 1.3 years before study entry ) . Study design . This was a 52-week , r and omized , double-blind , multinational study of ccHRT comprising three different dose combinations of E2V/MPA in 459 early postmenopausal non-hysterectomized women experiencing 30 or more moderate to severe hot flushes a week and /or vasomotor symptoms requiring treatment . Main outcomes measures . The primary endpoint was change in frequency and severity of moderate to severe hot flushes at 12 weeks . Secondary outcome measures included number of bleeding days and evaluation of tolerability . Results . The frequency of hot flushes was reduced by ≥70 % after one month ( P<0.001 for all doses at week 2 onwards ) , with little evidence of statistically different dose effects . Severity of flushing was also attenuated by  ccHRT . Mean number of bleeding days fell to < 1 per 28-day cycle at 52 weeks . Rates of amenorrhoea approached 80–90 % at the end of the study , but were significantly lower at several time points with the highest-dose regimen ( 2 mg E2V + 5 mg MPA ) than with the lower-dose options ( 1 mg E2V + 2.5 mg MPA and 1 mg E2V + 5 mg MPA ; P<0.05 ) . Adverse events declined in frequency over time with all regimens but throughout the study were more numerous with the highest-dose regimen than with lower doses ( P= 0.0002 ) . Conclusions . Continuous combined HRT was effective for the relief of climacteric symptoms in early postmenopausal women and was well tolerated Abstract Objectives : This study assessed the effects of oral porcine placental extract ( PPE ) on the  mild menopausal symptoms of climacteric women . Methods : In this 12-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study , 50 climacteric Japanese women were r and omized 1 : 1 to oral PPE ( 300 mg/day ) or placebo .  Menopausal symptoms were evaluated by using the Simplified Menopausal Index ( SMI ) , as were serum estradiol ( E2 ) and follicle stimulating hormone ( FSH ) levels . Blood biochemical and cellular and urinary tests were done to evaluate safety aspects of repeated oral administration of PPE . Results : The total SMI score of the PPE group was significantly more improved after 12 weeks than that of the placebo group ( p = 0.031 ) . This score and three subscores ( vasomotor , psychological , and somatic symptoms ) were significantly improved at 8 and /or 12 weeks compared with the initial values in the PPE group ( p < 0.05 ) . E2 and FSH levels were not improved in either group . No adverse events were observed . Conclusions : Oral PPE at 300 mg/day improved the mild menopausal symptoms of climacteric women . Since oral PPE did not improve serum E2 and FSH levels , PPE is thought not to ameliorate hormonal balance itself but to improve subjective feelings of climacteric women One hundred and ten ( 110 ) healthy early post-menopausal women with mild subjective vasomotor symptoms ( mean Kupperman index score 11 ) participated in a long-term , double-blind , placebo-controlled therapeutic trial . The effects of 2 hormone regimens were evaluated . Group I received percutaneous oestrogen therapy for 2 yr , opposed by oral micronized progesterone ( 200 mg ) during the second year , while Group II received oral 17 beta-oestradiol valerate together with cyproterone acetate ( CPA ) . The serum oestrogen concentrations differed markedly in the 2 treatment groups . In Group I the serum/oestrone/oestradiol ratio was 1 ( comparable to the pre-menopausal value ) , but in group II the ratio was greater than 5 . Despite the difference in the serum oestradiol and oestrone concentrations , the mean symptom scores were rapidly and similarly reduced in both treatment groups ( P less than 0.001 ) . They remained low throughout the study and were not significantly different from pre-menopausal values Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) .  Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p < 0.0001 ) . Conclusions . Adding methyl-testosterone to hormone therapy  improves quality of life and sexuality in post-menopausal women with sexual dysfunction Estrogen-only  menopausal hormone therapy ( HT ) increases the risk of endometrial cancer , but less is known about the association with other types of HT . Using Cox proportional hazards regression , the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospect i ve Investigation into Cancer and Nutrition between 1992 and 2000 . After a mean follow-up period of 9 years , 601 incident cases of endometrial cancer were identified . In comparison with never users of  HT  , risk of endometrial cancer was increased among current users of estrogen-only HT ( hazard ratio ( HR ) = 2.52 , 95 % confidence interval ( CI ) : 1.77 , 3.57 ) , tibolone ( HR = 2.96 , 95 % CI : 1.67 , 5.26 ) , and , to a lesser extent , estrogen-plus-progestin HT ( HR = 1.41 , 95 % CI : 1.08 , 1.83 ) , although risks differed according to regimen and type of progestin constituent . The association of HT use with risk was stronger among women who were older , leaner , or had ever smoked cigarettes . The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk . The increased risk associated with tibolone use requires further investigation OBJECTIVE : To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone ( 10 % ) combined with estriol ( 0.1 % ) + estradiol ( 0.25 % ) for relieving postmenopausal symptoms . METHODS : A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern . Confocal Raman spectroscopy of hormones in skin layers was performed . Clinical parameters , serum concentrations of estradiol and follicle-stimulating hormone , blood pressure , BI-RADS classification from bilateral mammography , and symptomatic relief were compared between baseline and 60 months post-treatment . Clinical trials.gov : NCT02033512 . RESULTS : An improvement in climacteric symptoms was reported in 92.5 % of women evaluated before and after 60 months of treatment . The serum concentrations of estradiol and follicle-stimulating hormone changed significantly ( p<0.05 ) after treatment ; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women . No adverse health-related events were attributed to this hormone replacement therapy protocol . CONCLUSION : The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause . This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women Objective : To examine whether the effect of postmenopausal hormone therapy ( HT ) on brain volumes in women aged 65–79 years differs depending on type 2 diabetes status during postintervention follow-up of a r and omized controlled clinical trial . Methods : The Women 's Health Initiative r and omized clinical trials assigned women to HT ( 0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate ) or placebo for an average of 5.6 years . A total of 1,402 trial participants underwent brain MRI  2.4 years after the trials ; these were repeated in 699 women 4.7 years later . General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes . Results : Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of −18.6 mL ( 95 % confidence interval [ CI ] −29.6 , −7.6 ) . For women without diabetes , this mean decrement was −0.4 ( 95 % CI −3.8 , 3.0 ) ( interaction p = 0.002 ) . This interaction was evident for total gray matter ( p < 0.001 ) and hippocampal ( p = 0.006 ) volumes . It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications . Conclusions : For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes , prescription of postmenopausal HT is associated with lower gray matter ( total and hippocampal ) volumes . Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women Introduction Since hormone replacement therapy given for long periods is now recognised to produce serious side effects , patients with troublesome vasomotor symptoms  are increasingly using non-hormonal treatment including acupuncture . Several r and omised controlled trials have shown that acupuncture reduces menopausal symptoms in patients experiencing the normal climacteric . It may have this effect by raising serotonin levels which alter the temperature set point in the hypothalamus . Vasomotor symptoms can be extreme in breast cancer patients and patients with prostate cancer who are undergoing anticancer therapy . The safety of some herbal medicines and phytoestrogens has been question ed , as they could potentially interfere adversely with the bioavailability of tumouricidal drugs . A previous study reports short term benefit from acupuncture , and the aim of this report is to describe our approach to long term treatment . Acupuncture Approach After piloting several approaches , six weekly treatments were given initially at LI4 , TE5 , LR3 and SP6 and two upper sternal points , but avoiding any limb with existing lymphoedema or prone to developing it . If there were no contraindications , patients were given clear instructions on how to perform self acupuncture using either semi-permanent needles or conventional needling at SP6 , weekly for up to six years , for long term maintenance . Audit Methods and Results A retrospective audit of electronic records was carried out by a doctor not involved in treatment . A total of 194 patients were treated , predominantly with breast and prostate cancer . One hundred and eighty two patients were female . The number of pre-treatment hot flushes per day was estimated by the patient : in the 159 cases providing adequate records , the mean was 16 flushes per day . Following treatment , 114 ( 79 % ) gained a 50 % or greater reduction in hot flushes and 30 ( 21 % ) a less than 50 % reduction . Treatment was ab and oned in those who responded poorly or not at all . The duration of treatment varied from one month to over six years with a mean duration of nine months . Seventeen patients ( 9 % ) experienced minor side effects over the six year period , mostly minor rashes ; one patient described leg swelling but this was likely to be due to a concurrent fracture . Conclusion Acupuncture including self acupuncture is associated with long term relief of vasomotor symptoms in cancer patients . Treatment is safe and costs appear to be low . An algorithm is presented to guide clinical use . We recommend the use of self acupuncture with needles at SP6 in preference to semi-permanent needles in the first instance , but poor responders use indwelling studs if they fail to respond adequately to self acupuncture with regular needles . Point location may be of less importance than the overall ‘ dose ’ , and an appropriate minimum dose may be required to initiate the effect Background Natural estrogen decline leads to vasomotor symptoms ( VMS ) . Hormone therapy alleviates symptoms but increases cancer risk . Effective treatments against VMS with minimal cancer risks are needed . We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS , assessed for the first time by 24hour ambulatory skin conductance ( SC ) Methods and results We conducted a parallel , double blind , r and omised control trial of 62 peri-menopausal women aged 40–65 , reporting ≥ 5 hot flushes/day and follicle stimulating hormone ≥35 IU/L. Participants received either twice daily treatment with bioavailable RC extract ( RCE ) , providing 34 mg/d isoflavones and probiotics , or masked placebo formulation for 12 weeks . The primary outcome was change in daily hot flush frequency ( HFF ) from baseline to 12 weeks using 24hr SC . Secondary outcomes were change in SC determined hot flush intensity ( HFI ) , self-reported HFF ( rHFF ) and hot flush severity ( rHFS ) , blood pressure and plasma lipids . A significant decrease in 24hr HFF ( P < 0.01 ) and HFI ( P<0.05 ) was found when comparing change from baseline to 12 months of the RCE ( -4.3 HF/24hr , CI -6.8 to -2.3 ; -12956 μS s-1 , CI -20175 to -5737 ) with placebo ( 0.79 HF/24hr , CI -1.56 to 3.15 ; 515 μS s-1 , CI -5465 to 6496 ) . rHFF was also significantly reduced ( P < 0.05)in the RCE ( -2.97 HFs/d , CI -4.77 to -1.17 ) group compared to placebo ( 0.036 HFs/d , CI -2.42 to 2.49 ) . Other parameters were non-significant . RCE was well tolerated . Conclusion Results suggest that moderate doses of RCE were more effective and superior to placebo in reducing physiological and self-reported VMS . Findings support that objective physiological symptom assessment methods should be used together with self-report measures in future studies on menopausal VMS . Trial registration Clinical Trials.gov Objective This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation , Dang Gui Buxue Tang ( DBT ) , with short-term menopausal symptoms and quality of life in local postmenopausal women . Methods A r and omized , double-blind , multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats . The participants were r and omized to receive DBT preparations at 1.5 , 3.0 , or 6.0 g/day for 12 weeks . The primary outcomes were vasomotor symptoms , Greene Climacteric Scale ( GCS ) score , and Menopause-Specific Quality of Life ( MENQOL ) score . Secondary outcomes included serum hormones and lipids . Results There were between-group differences in psychological/psychosocial ( P = 0.015 , GCS ; P = 0.013 , MENQOL ) and somatic/physical ( P = 0.019 , GCS ; P = 0.037 , MENQOL ) domains , and improvement was significantly greatest ( P < 0.05 ) in the 6.0 g/day dose group . The frequency and severity of hot flashes and night sweats were significantly reduced in the 3.0 g/day ( 14.5%-21.2 % , P < 0.05 , hot flashes ; 28.6%-39.6 % , P < 0.05 , night sweats ) and 6.0 g/day ( 34.9%-37.4.0 % , P < 0.01 , hot flashes ; 10.1%-12.8 % , P < 0.01 , night sweats ) dose groups . The female hormones follicle-stimulating hormone , luteinizing hormone , and 17&bgr;-estradiol , as well as the lipids total cholesterol , triglycerides , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol , were not significantly different within groups and between groups . Conclusions DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline . The treatment was well tolerated , with no serious adverse events noted during the 12-week intervention period . The changes do not affect hormones and lipid profiles Purpose To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms . Methodology A r and omized , single blind , four arm , parallel assignment study was conducted in VMMC and SJH , New Delhi , India . 200 Indian menopausal women were recruited and assigned into four treatment groups viz . , estradiol valerate ( E2V ) , conjugated equine estrogen ( CEE ) , isoflavones and Placebo group . The statistical significance of categorical variables was determined by Chi-square , Fisher ’s exact test . In case of quantitative variable parametric test Student ’s t test was used . In case of quantitative variables where data are not normally distributed , Kruskal – wallis test and Wilcoxon Mann – Whitney test were used . Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups . Results Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes . 91.9 % decrease was observed in mean hot flash score in the E2V group after 24 weeks of treatment , 89.2 % in the CEE group , 60.42 % decrease in the isoflavones group . While placebo led to 47.9 % decrease in mean hot flash score . After 24 weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group . No serious side effect was reported in any of the groups . Conclusion Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24 weeks . However , it seems more reasonable to replenish with less costly and bio-identical hormone , i.e. micronized estradiol valerate which is equally effective . Trial registryThe trial was registered under Clinical trial registry of India prospect ively ( number : CTRI/2012/04/002566 ) Background . The unexpected results of the Women 's Health Initiative study have decreased the use of conventional hormone therapy ( HT ) , changing physicians ' and patients ' attitudes towards HT and increasing their interest in alternative options . Objective . The present study aim ed to evaluate the effect of isoflavones contained in red clover extracts ( Trifolium pratense ) on menopausal symptoms , lipids and vaginal cytology in menopausal women . Methods . Sixty postmenopausal women aged > 40 years , non-users of HT , with Kupperman index score ⩾15 , were double-blindly r and omized to receive either a commercially available red clover isoflavone supplement ( 80 mg/day ) or placebo for 90 days . Subsequently , after a 7-day washout period , subjects switched to receive the opposite treatment for a further 90 days . Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline , 90 and 180 days . Results . Fifty-three women ( 88.3 % ) completed the trial . Mean age was 51.3 ± 3.5 years , 69.7 % of the women were aged 50 years or more . There was no significant effect on body mass index , weight or blood pressure after either treatment phase . Baseline Kupperman index score decreased significantly after each treatment phase , with the decrease more pronounced after the isoflavone phase ( baseline : 27.2 ± 7.7 ; after isoflavone : 5.9 ± 3.9 ; after placebo : 20.9 ± 5.3 , p < 0.05 ) . Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic , cornification and basal cell maturation indices . Mean total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels also decreased ; however , only the latter was significantly lower compared with placebo . Conclusions . Compared with placebo , red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels
Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects .
There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes .
There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects .
No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack , stroke and breast cancer .
BACKGROUND Various hormone therapies ( HT ) are available to treat  menopausal vasomotor symptoms .
Bioidentical hormones are chemically identical to those produced by the human body , and several types are well-tested and available on prescription .
Many women have opted for bioidentical hormone therapy ( BHT ) on the assumption that it is safer than other forms of HT .
We evaluated the evidence .
OBJECTIVES To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms .