17β-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study. Beliefs about bioidentical hormone therapy: a cross-sectional survey of pharmacists. Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study Evidence-based review of therapies at the menopause. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial Reproductive hormone exposure timing and ischemic heart disease: Complicated answers to a simple question. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial. Aerobic exercise as a treatment for vasomotor menopausal symptoms: randomised controlled trial protocol. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. 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. Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo Vasomotor Symptom Relief by Soy Isoflavone Extract Tablets in Postmenopausal Women: A Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Study Characteristics of hormone therapy, cognitive function, and dementia Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial. How best is to discontinue postmenopausal hormone therapy: immediate or tapered?
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
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 .