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. 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. Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo Evidence-based review of therapies at the menopause. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women. 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 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 Women's willingness to accept perceived risks for vasomotor symptom relief. [Clinical effects of hormone replacement therapy with estradiol valerate and cyproterone acetate in perimenopausal women]. Hormone therapy in menopausal women with cognitive complaints Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Hormonal and psychological treatment: therapeutic alternative for menopausal women? Efficacy and tolerability of continuous combined hormone replacement therapy in early postmenopausal women 17β-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review.
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 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 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 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 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 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 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 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 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 BACKGROUND In perimenopause many women complain of psychogenic and organic disorders often connected with initial and increasing levels of hypoestrogenism . In this study we evaluated the effects of hormone replacement therapy ( HRT ) in symptomatic women in perimenopause . METHODS We enrolled 100 healthy and symptomatic women who were r and omly distributed to two groups for a 12-month study . Group A : 50 patients received HRT with estradiol valerate and cyproterone acetate ( Pausene(R ) ) ; Group B : 50 patients were used as a control group ( treated with Cacit Vitamin D30(R ) ) . A number of clinical and instrumental tests were performed at 0 , 6 and 12 months to evaluate any changes in vasomotor and urogenital symptoms , bone and serum homeostasis and possible sexual disorders . The statistical analysis was performed using the c2 test . RESULTS The group of women receiving HRT showed a significant reduction in vasomotor clinical symptoms ( p<0.001 ) and sexual disorders ( p<0.002 ) ; this was not reflected in the control group where libido decreased steadily with apparent slight improvements only at the end of the study . The urogenital disorders disappeared almost completely in Group A , whereas they diminished in Group B. HRT patients also showed a slight increase ( p<0.001 ) in the initial value of BMD ( bone mineral density ) , a reduction in the marker for bone turnover and an improved lipid profile ( p<0.05 ) . These changes were unfortunately not noted in Group B. CONCLUSIONS On the basis of these results we conclude that HRT appeared to have a beneficial effect on perimenopausal clinical symptoms over the 12-month period , leading to marked improvements in the psychophysical wellbeing of symptomatic women in perimenopause 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 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 ) In a double-blind , placebo-controlled study , 109 patients suffering from local and vasomotor postmenopausal complaints were r and omly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol ( E3 ) or a placebo . The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially , followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period . The effectiveness of the therapy was assessed on the basis of question naires ( Kupperman index for vasomotor complaints and an original urogenital index for local complaints ) and gynaecological examinations which included assessment s of vaginal cytology , vaginal pH and Döderlein bacilli . To rule out induced endometrial proliferation , endometrial biopsies were performed in 50 women before and after the study . The vaginal depot ( E3 ) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints , including hot flushes . Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation . Taking into account the minimal rate of adverse effects , the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints 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 . 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 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
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 .