Aerobic exercise as a treatment for vasomotor menopausal symptoms: randomised controlled trial protocol. Androgens and estrogens in relation to hot flushes during the menopausal transition. A Pilot Study of the Effects of Phytoestrogen Supplementation on Postmenopausal Endometrium Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study The effects of micronutrient supplementation on vasomotor symptoms in 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. Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment Efficacy of a Proprietary Trigonella foenum‐graecum L. De‐Husked Seed Extract in Reducing Menopausal Symptoms in Otherwise Healthy Women: A Double‐Blind, Randomized, Placebo‐Controlled Study The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women Isoflavone treatment for acute menopausal symptoms [The effects of phytoestrogen therapy on the endometrium in postmenopausal women]. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: Randomized, controlled, double-blind pilot study Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. A randomized, double-blind, placebo-controlled trial of Chinese herbal medicine granules for the treatment of menopausal symptoms by stages Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study Dietary soy supplementation and phytoestrogen levels. Effectiveness of a modified version of the applied relaxation technique in treatment of perimenopausal and postmenopausal symptoms A cognitive model of menopausal hot flushes and night sweats. Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms
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 In this paper , the association of hormones to vasomotor complaints during the menopausal transition is discussed . Fifty-seven regularly menstruating women without history of hormone replacement therapy ( HRT )  were selected for a longitudinal , prospect i ve study around the menopausal transition . The mean age at the start of the study was 51.3 ( + /-2.0 ) years . At intervals of 12 months all women went through a semi-structured interview and filled in question naires .  Venous blood sample s were collected every 12-month for analyses of estradiol ( E2 ) , testosterone , and rostendione , dehydroepi and rosterone-sulphate ( DHEA-S ) , follicle stimulating hormone ( FSH ) , thyrotropin ( TSH ) , and luteinizing hormone ( LH ) . Vasomotor complaints were tested using questions about hot flushes and bouts of sweating in terms of occurrence , frequency and degree of distress . Forty-six percent of the subjects reported hot flushes and bouts of sweating before menopause , increasing to 67 % during the first year after menopause and 49 % in the second year postmenopause . Low levels of estradiol and high levels of FSH were associated with vasomotor complaints before menopause . During menopause high levels of TSH were related to vasomotor complaints . The first year after menopause , women , who at this point achieved hot flushes , were characterised by high levels of E2 , but declining and low levels of FSH , but increasing . Postmenopausal , high levels of testosterone and DHEA-S seemed to protect against vasomotor symptoms . Our most important finding was , that among women who achieved hot flushes at the first assessment postmenopause , the high and rogen levels was a significant predictor of recovery from hot flushes at the last assessment , 1 year later Objective : This study was design ed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy , to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms , and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology . Methods : We performed a prospect i ve , double-blinded , r and omized , placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplemtation versus placebo in postmenopausal women . Baseline endometrial biopsies were performed and , if adequate , nonhyperplastic , noncancerous , and non-ovulatory , subjects were r and omly assigned to receive daily placebo or soy cereal supplementation for 6 months . Study subjects completed baseline and weekly dietary , symptom , and side effect logs . Repeat endometrial biopsies were obtained at 6 months . Results : Subjects were recruited from January 1998 through June 2000 . Twenty-seven subjects were r and omized , and 19 completed the study . One ( 3.7 % ) baseline endometrial sample was weakly proliferative . All other baseline and final biopsies were consistent with atrophic , inactive endometrium . The maximum risk of endometrial stimulation with phytoestrogens is 35 % . Hot flushes , night sweats , and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group . Insomnia was more common in the treated group . There were no other statistically significant differences in symptoms or side effects . Conclusion : Phytoestrogens did not cause stimulation of the endometrium . Insomnia was more frequent over the 6-month study in the soy group , whereas hot flushes , night sweats , and vaginal dryness improved from baseline in the placebo group but not in the soy group Objective : Vasomotor symptoms (VMS)(hot flashes , night sweats ) are associated with natural or surgically or chemotherapy-induced menopause , the latter occurring frequently in women treated for breast cancer . To manage VMS , some women seek alternatives to menopausal hormone therapy , such as supplements or modified food choices . The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber , fat , and selected soy-containing foods , and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer , adjusting for covariates . Design : Using multivariate logistic regression , data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women 's Healthy Eating and Living r and omized , controlled trial of a high-vegetable , high-fiber , reduced-fat diet .  Results : Being peri- or postmenopausal , using tamoxifen , having low social support or depressive symptoms , and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment . Increased symptom severity after 12 months was significantly associated with higher body mass index , tamoxifen use , and smoking . Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake ; no decrease was observed in women who were peri- or postmenopausal , using tamoxifen , or had low fat intake or low social support . Conclusions High dietary fiber intakes , premenopausal , and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer ABSTRACT Objective Estrogen is the most effective treatment for vasomotor symptoms . Given its potential risks , herbal preparations and nutritional supplements have been developed as alternative remedies . The main aim of this double-blind , r and omized , placebo-controlled trial was to assess any impact of a nutritional supplement containing 12 vitamins and nine minerals on the frequency and severity of hot flushes in postmenopausal women over a 3-month period . Subjects and methods Ninety-one postmenopausal women were r and omized to either the placebo ( n = 45 ) or the treatment arm ( n = 46 ) . Seventy out of the 91 women completed the study ( 36 from the treatment group and 34 from the placebo group ) . At baseline and the 14-week post-intervention assessment s , study participants completed question naires on the frequency and severity of hot flushes and night sweats , the Profile of Mood State question naire , the World Health Organization Quality of Life Question naire , the National Adult Reading Test and the Rey Auditory-Verbal Learning Test . Between assessment s , the women also completed hot flush diaries . Results There was a significant decrease ( p < 0.01 ) in the number ( ±st and ard error of the mean ) of hot flushes experienced per week for treatment ( pre 31.3 ± 4.7 ; post 23.1 ± 4.8 ) and placebo groups ( pre 28.1 ± 4.7 ; post 17.3 ± 4.0 ) . A significant decrease ( p < 0.001 ) in the number of night sweats experienced per week was also observed in the treatment ( pre 6.1 ± 1.0 ; post 4.2 ± 0.7 ) and placebo groups ( pre 5.9 ± 0.7 ; post 3.7 ± 0.7 ) . Conclusions This study demonstrates a significant placebo effect on hot flushes and night sweats , as consistent with other studies . The micronutrient supplement containing 21 vitamins and minerals was not superior over placebo in effects on hot flushes and night sweat experiences 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 Objective We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich ( 80.4 mg/day ) and isoflavone-poor ( 4.4 mg/day ) soy protein isolate treatment in perimenopausal women . Design In this double-blind 24-week study , 69 women were r and omized to treatment : isoflavone-rich soy protein ( n = 24 ) , isoflavone-poor soy protein ( n = 24 ) , or whey protein control ( n = 21 ) . A Menopausal Index was used to assess change in hot flushes and night sweats , as well as other symptoms , at baseline , week 12 , and week 24 . Results Repeated measures analysis of variance indicated no treatment effect on change in hot flush ( p = 0.18 ) and night sweat ( p = 0.92 ) frequency , whereas there was a significant decline in hot flush ( p = 0.0003 ) and night sweat ( p = 0.0007 ) frequency with time in all treatment groups . & khgr;2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point , as well as no treatment effect on frequency or severity of other vasomotor symptoms . At the completion of the study , we found no treatment effect on retrospective perception of frequency , duration , or severity of hot flushes or night sweats . Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms , this indicated either a placebo effect or simply an improvement in symptoms during the study . Conclusion In this study , we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms & NA ; Trigonella foenum‐graecum seed extract has demonstrated hormone modulatory activity , providing biological plausibility for relieving menopausal symptoms . The study aim ed to assess efficacy of a st and ardized T. foenum‐graecum de‐husked seed extract in reducing menopausal symptoms in healthy aging women . The study was a double‐blind , r and omized , placebo‐controlled trial that recruited 115 women aged 40 to 65 years of which 59 were allocated to active ( n = 54 completed ) and 56 to  placebo  ( n = 50 completed ) . Active treatment was T. foenum‐graecum de‐husked seed extract , 600 mg per day for 12 weeks . Outcome measures included Menopause‐Specific Quality of Life ( MENQOL ) question naire , frequency of hot flushes and night sweats and serum estradiol levels . There was a significant reduction in menopausal symptoms in the active group compared with placebo as assessed by total MENQOL score ( p < 0.001 ) ; reflected by significant improvements in the vasomotor ( p < 0.001 ) , psychosocial ( p < 0.001 ) , physical ( p < 0.001 ) and sexual symptoms ( p < 0.001 ) domains . Vasomotor outcomes correlated with hot flushes , the active group reporting significantly less daytime hot flushes and night sweats at 12 weeks ( p < 0.001 ) . The average estradiol levels were similar in both the active group and placebo group after treatment . This study demonstrated that this proprietary T. foenum‐graecum de‐husked seed extract may reduce menopausal symptoms in healthy women Objective . To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women . Methods . One hundred and nine postmenopausal women aged 40 or more were assigned to r and omly receive either two daily capsules of the active compound ( 80 mg red clover isoflavones , Group A ) or placebo of equal appearance ( Group B ) for a 90-day period . After a washout period of 7 days , medication was crossed over and taken for 90 days more . Daily hot flush and night sweat frequency and overall menopausal symptom intensity ( Kupperman Index ) were measured at baseline , 90 , 97 and 187 days . Results . Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline . All indices significantly decreased after red clover phase in Group A , corresponding , respectively to a 73.5 % , 72.2 % and 75.4 % average decrement . These decrements were significantly higher than those observed for Group B after placebo phase ( 8.2 % , 0.9 % and 6.7 % respectively ) . In Group A , after washout and placebo phases all values significantly increased . In Group B , all indices remained similar after placebo and washout phases , however significantly dropping after red clover treatment . These values were also significantly lower than those observed in Group A after placebo phase . No side effects were encountered after treatment with the active compound or placebo . Conclusion . Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women Objective : The onset of climacteric symptoms ( hot flashes and night sweats ) is the primary reason for perimenopausal women to start hormone therapy . The association of a lower incidence of postmenopausal symptoms with high intake of soybeans in Asian women suggests that phytoestrogens are an alternative to estrogen therapy . The main effective compounds in soybean are isoflavones , which have a higher binding affinity to estrogen receptor & bgr ; than to estrogen receptor & agr;. The aim of present study was to evaluate the effects of isoflavone treatment in postmenopausal women . Design : This was a double-blind prospect i ve study . Sixty healthy postmenopausal women were r and omly assigned by computer into two groups to receive 60 mg isoflavones or placebo daily for 3 months . Before and after treatment , climacteric symptoms were recorded ; serum was collected to measure the levels of lipoprotein lipids , estradiol , and follicle-stimulating hormone ; and biopsy specimens from endometrium and breast were analyzed to investigate the expression level of steroid receptors and proliferation . Endometrial thickness was measured by ultrasound . Results : Fifty-one women finished the 12-week study . In women receiving 60 mg isoflavones daily , hot flashes and night sweats were reduced by 57 % and 43 % , respectively . The treatment did not change the levels of circulating estradiol or follicle-stimulating hormone . Immunohistochemical staining of endometrial and breast biopsy specimens revealed that isoflavones did not affect expression levels of steroid receptors ; estrogen receptors & agr ; , & bgr ; , and & bgr;cx ; progesterone receptors A and B ; or the proliferation marker Ki67 . No side effects on body weight or lipoprotein lipids were observed . Conclusions : This short-term prospect i ve study implies that isoflavones could be used to relieve acute menopausal symptoms AIM The purpose of the present study was to carry out a comparative histological analysis of the endometrium in postmenopausal women who made use of phytoestrogens in order to assess the efficacy and possible side effects of this therapy . METHODS This study was carried out by forming 2 groups in order to compare the results . One group was given a dietary supplement of phytoestrogens for 24 months , whereas the other was given a placebo for the same period of time . At the beginning of this study endometrial bioptical sample s were taken from those patients who had been previously selected at our University Centre . This study was started only with those postmenopausal patients whose bioptical sample was histologically suitable , and it was neither hyperplastic , nor cancerous and nor secretive . During these 24 months there have been frequent contacts aim ed at verifying the st and ard therapeutic behaviour , symptoms and appearance of side effects . At the end of the study new and final bioptical sample s of endometrium were taken from both groups . RESULTS One-hundred and forty-one patients completed the study . Five patients ( 3.4 % ) who were su bmi tted to phytoestrogens therapy showed a weak proliferative endometrium bioptical sample . All the other biopsies at the beginning and at the end of the study showed an atrophic and inactive sample . Hot flushes , night sweats , vaginal dryness and dyspareunia improved at the end of the study for the group treated with phytoestrogens as compared to the one treated with a placebo . Although there have not been very significant differences ias to symptoms and side effects , it was noted that insomnia was the most common symptom in the group treated with non-hormonal therapy based on phytoestrogens . CONCLUSIONS Phytoestrogens did not cause any sensitive and worrisome stimulation of the endometrial mucosa . Insomnia was more frequent in the group treated pharmacologically in the 24 months of the study , whereas hot flushes , night sweats , vaginal dryness and dyspareunia persisted or increased as compared to the beginning of the study in the group treated with a placebo , but this did not occur for the group treated with phytoestrogens Objective : To evaluate in a 12-month , prospect i ve , r and omized , double-blind , placebo-controlled study whether pure administration of the phytoestrogen genistein ( 54 mg/d ) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium . Design : A total of 389 participants met the main study criteria and were r and omly assigned to receive the phytoestrogen genistein ( n = 198 ) or placebo ( n = 191 ) . About 40 % of participants in both groups did not suffer from hot flushes , and the evaluation was performed in a subgroup of 247 participants ( genistein , n = 125 ; placebo , n = 122 ) . Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy . Endometrial thickness was evaluated by ultrasonography . The maturation value was also used to determine hormonal action on the vaginal cells . Results : There were no significant differences in age , time since menopause , body mass index , and vasomotor symptoms between groups at baseline ( 4.4 ± 0.33 hot flushes per day in the genistein group and 4.2 ± 0.35 hot flushes per day in the control group ) . The effect was already evident in the first month and reached its peak after 12 months of genistein therapy ( −56.4 % reduction in the mean number of hot flushes ) . Furthermore , there was a significant difference between the two groups at each evaluation time ( 1 , 3 , 6 , and 12 months ) . No significant difference was found in mean endometrial thickness and maturation value score between the two groups , either at baseline or after 12 months . Conclusions : The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium Objective . To determine the efficacy and safety of the herbal formula Phyto-Female Complex ( SupHerb , Netanya , Israel ; ingredients : st and ardized extracts of black cohosh , dong quai , milk thistle , red clover , American ginseng , chaste-tree berry ) for the relief of menopausal symptoms . Methods . A r and omized , double-blind , placebo-controlled trial in 50 healthy pre and postmenopausal women , aged 44–65 years , to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months . A structured question naire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period , followed by biochemical tests , breast check , and transvaginal ultrasonography . Results . The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group . The effect of treatment improvements in menopausal symptoms increased over time ; by 3 months there was a 73 % decrease in hot flushes and a 69 % reduction of night sweats , accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality . Hot flushes ceased completely in 47 % of women in the study group compared with only 19 % in the placebo group . There were no changes in findings on vaginal ultrasonography or levels of relevant hormones ( estradiol , follicle-stimulating hormone ) , liver enzymes or thyroid-stimulating hormone in either group . Conclusion . Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women , at least for 3 months ' use OBJECTIVE To evaluate the preliminary efficacy and safety of Pueraria mirifica ( Kwao Keur Kao ) , phytoestrogen , for the alleviation of climacteric symptoms . MATERIAL AND METHOD Perimenopausal women attending with climacteric symptoms , such as hot flushes and night sweats , were invited to join the present study , conducted at the Menopausal Clinic , Hat Yai Regional Hospital . The patients were voluntarily enrolled and r and omly received the raw material of Pueraria mirifica , oral 50 and 100 mg capsule , once daily for six months , as an open-label study . RESULTS Of the 10 enrolled patients , 8 cases were completely evaluated . The modified Greene climacteric scale ( MGCS ) was satisfactorily decreased in both groups . The average scale declined from 44.1 at baseline , to be 26 , 17 , and 11.1 at 1- , 3- , and 6- month follow-up respectively . No other laboratory abnormalities , except one case had transiently increased the creatinine level , and one case of increased blood urea nitrogen . The mean serum estradiol was slightly increased , while the mean serum follicle-stimulating hormone ( FSH ) and luteinizing hormone ( LH ) were nearly stable . CONCLUSION Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal . women , but the data is insufficient to draw definite conclusions regarding the estrogenic effect PURPOSE Vasomotor symptoms , such as hot flashes and night sweats , in breast cancer survivors are often worsened by chemotherapy and tamoxifen , and /or the discontinuation of hormone replacement therapy at diagnosis . This study evaluated the acceptability and effectiveness of a soy beverage containing phytoestrogens as a treatment for hot flashes in postmenopausal women with breast cancer . METHODS A r and omized , placebo-controlled , double-blind clinical trial was conducted in postmenopausal women with moderate hot flashes who were previously treated for early-stage breast cancer . Women were stratified for tamoxifen use and r and omized to a soy beverage ( n = 59 ) containing 90 mg of isoflavones or to a placebo rice beverage ( n = 64 ) . Women recorded the number and severity of hot flashes daily with a daily menopause diary for 4 weeks at baseline and for 12 weeks while consuming 500 mL of a soy or placebo beverage . RESULTS There were no significant differences between the soy and placebo groups in the number of hot flashes or hot flash scores . However , presumably because of a strong placebo effect , both groups had significant reductions in hot flashes . Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy . The mean serum genistein concentration at 6 weeks was significantly higher in women who consumed soy ( 0.61 + /- 0.43 micromol/L ) compared with placebo ( 0.43 + /- 0.37 micromol/L ) ( P = .02 ) . Overall acceptability and compliance were high and similar in both groups . CONCLUSION The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo . Future research into other compounds is recommended to identify safe and effective therapies for hot flashes in breast cancer survivors Objective : The study aims to evaluate the effectiveness and safety of Chinese herbal medicine granules Danzhi Qing’e formula ( DZQE ) , Erzhi formula ( EZ ) , and their combination ( Combined formula ) in the treatment of menopausal symptoms at different stages of menopause . Methods : Women between the ages of 40 to 60 years , who met menopausal symptoms diagnostic criteria and experienced hot flushes at least 14 times/week in the last 4 weeks , were recruited to participate in a stratified r and omized , double-blind , placebo-controlled  clinical trial ( n = 389 ) . They received a treatment period of 8 weeks and were followed up for 4 weeks . Participants were categorized into two subgroups : 197 in the perimenopausal subgroup ( menstrual disorder to 1 y after amenorrhea ) and 192 in the early postmenopausal subgroup ( 1 - 5 y after amenorrhea ) . Participants were r and omly assigned to placebo or one of the three herbal formula treatments . The primary outcome instrument was the Menopause-Specific Quality of Life ( MENQOL ) question naire . Results : When analyzing the two subgroups together , DZQE markedly decreased the MENQOL total score at the end of 12th week with statistical significance ( P = 0.02 ) and improved vasomotor symptoms after 8 weeks treatment and 4 weeks follow-up ( P < 0.05 ) . What is more , the combined formula also greatly improved the participants ’ vasomotor symptoms compared with placebo after the 4 weeks follow-up . No statistically meaningful difference was observed in any other outcomes among the groups . The results of subgroup analysis showed that DZQE and Combined formula were more effective than placebo in improving MENQOL total score for perimenopausal women at the end of week 12 . For typical menopausal symptoms such as hot flushes and night sweats , DZQE displayed more favorable effects on early postmenopausal participants . Compared to placebo , the DZQE both showed statistically significant differences after 8 weeks treatment and 4 weeks follow-up . Although at the end of 12th week , DZQE also had better effects than placebo in the perimenopausal subgroup on vasomotor symptoms . Participants in the EZ group did not show a significant difference of any domains in MENQOL compared with participants in the placebo group . Conclusions : The DZQE formula improves the quality of life for menopausal women , especially for those with vasomotor symptoms during the whole menopausal period . The DZQE and EZ combination formula is effective only on perimenopausal symptoms OBJECTIVE To evaluate the efficacy comparison of Pueraria mirifica ( PM ) , name in Thai is Kwao Kruea Khao , against conjugated equine estrogen ( CEE ) with/without medroxyprogesterone acetate ( MPA ) in the treatment of perimenopuasal women with climacteric symptoms . MATERIAL AND METHOD Perimenopausal women attending the Menopausal clinic of Hat Yai Regional Hospital were voluntarily recruited . The vasomotor symptoms such as hot flushes and night sweats , as well as other unpleasant symptoms , urogenital and psychological symptoms , were also assessed . Patients were voluntarily enrolled and r and omly received daily 50 mg raw material of PM , Group A , or daily 0.625 mg of conjugated equine estrogen ( CEE ) with/without 2.5 mg of medroxyprogesterone acetate ( MPA ) , Group B , depend on non-hysterectomized/hysterectomized condition . RESULTS Seventy-one patients were enrolled . Eleven of those were excluded for failing to complete the initial work-up and follow-up . Sixty cases were evaluated , 30 cases in Group A and 30 cases in Group B. After medication , the mean of modified Greene climacteric scale ( MGCS ) in Group A/Group B had decreased from 29.0/32.26 to 17.86/18.1 , 12.56/9.57 and 9.9/8.16 at 1- , 3- , and 6- month respectively . The clinical satisfaction using MGCS was not statistically significant between PM ( Group A ) and CEE with/without MPA ( Group B ) in the alleviation of climacteric symptoms ( p-value > 0.05 ) . There were no statistically significant changes of three serum markers : estradiol , follicle-stimulating hormone ( FSH ) , and luteinizing hormone ( LH ) between both groups . CONCLUSION PM , containing phytoestrogens , has estrogenic effect as similar as CEE , and can alleviate the climacteric symptoms in perimenopausal women . PM demonstrates great promise in the treatment of climacteric symptoms . However , optimal doses should be clinical ly assessed to meet appropriate individual responses Objective To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of  vasomotor symptoms ( hot flashes and night sweats ) in peri- and postmenopausal women . Design A double-masked , r and omized , controlled , clinical trial was conducted . A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were r and omized into one of three groups . In all groups , participants consumed a daily supplement containing 25 g of soy protein and were r and omly assigned to one of three groups : ( a ) isoflavone extracted soy protein ( control ) , ( b ) soy protein with a medium dose of isoflavones ( 42 mg/day ) , or ( c ) soy protein with a higher dose of isoflavones ( 58 mg/day ) . The primary outcome measure in this trial was change in reported vasomotor symptoms . Results A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups . No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone , middle isoflavone , or control groups . The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy . Conclusions These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women OBJECTIVE To investigate the relationship between levels of  phytoestrogens  in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen . METHODS Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked , parallel , placebo-controlled trial . The effect of soy supplementation on menopausal symptoms in this study population was reported previously . RESULTS Serum levels of genistin , daidzin , and equol were significantly higher in women after soy diet supplementation ( + 756 % , + 593 % , + 1008 % , and 57 % respectively ) . The concentration of enterolactone in the soy group was increased by 57 % compared with baseline , but the difference with placebo was not statistically significant . The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes . Vaginal maturation indices did not change in the soy group . CONCLUSION Phytoestrogen levels increased in women who consumed soy supplement , but that does not fully explain climacteric symptom reduction . It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes Background Awareness of the risks associated with hormone therapy for menopausal symptoms has sparked a global decline in this treatment . Alternative treatments to relieve menopausal symptoms are therefore required . The applied relaxation ( AR ) technique has proven to be successful for symptom amelioration , but requires participation in 12 weekly classes . The purpose of this study was to determine the effectiveness of a modified relaxation version ( MR ) of AR for treatment of hot flashes , night sweats , and sleep disturbances . Methods We conducted a12-week , r and omized , parallel , open-label , controlled trial in perimenopausal and postmenopausal women visiting the menopausal clinic . Participants were r and omly assigned to an MR or AR group . The MR group ( n=36 ) received a single session of ( MR ) training and the AR group ( n=35 ) received conventional 12-week training . Participants were instructed to practice the techniques daily at home for 12 weeks . The main outcome was the measure on the severity scale and frequency of hot flashes , night sweats , and sleep disturbances . Results All participants completed the study .  Total severity scores in both groups decreased after 12 weeks , but there was no difference between the groups ( P=0.93 ) . The severity score for hot flashes in the MR group decreased more than in the AR group ( P=0.02 ) . The severity scores for night sweats and sleep disturbances decreased in both groups . The frequency of hot flashes , night sweats , and sleep disturbances were also decreased in both groups . Conclusion A shorter , modified version of the AR was equally effective or slightly better than the conventional AR for the relief of hot flashes , night sweats , and sleep disturbances in perimenopausal and postmenopausal women . Recommendations for future research include confirmatory studies and trials with larger sample Hot flushes and night sweats ( HF/NS ) are commonly experienced by mid-aged women during the menopause transition . They affect approximately 70 % of women but are regarded as problematic for 15 - 20 % largely due to physical discomfort , distress , social embarrassment , and sleep disturbance . There is a need for effective and acceptable nonmedical treatments for menopausal symptoms due to the declining use of hormone therapy ( HT ) following publication of the Women 's Health Initiative and other prospect i ve studies which associated HT use with increased risk of stroke and breast cancer . HF/NS are an example of a physiological process embedded within , and moderated by , psychological processes , as evidence d by discrepancies between subjective experiences and physiologically measured symptoms . We describe a cognitive model of menopausal hot flushes that can explain symptom perception , cognitive appraisal , and behavioral reactions to symptoms . Theoretically , the model draws on symptom perception theory , self-regulation theory , and cognitive behavioral theories . The model can be used to identify the variables to target in psychological interventions for HF/NS and to aid underst and ing of possible mediating factors . As part of Phase II intervention development , we describe a cognitive behavioral treatment which links the bio-psycho-social processes specified in the model to components of the intervention Objective : To compare a novel vaginal ring releasing estradiol acetate ( Menoring ® ; Galen Holdings ) with oral estradiol for relief of moderate to severe vasomotor symptoms in healthy postmenopausal women . Design : This was a prospect i ve , double-blind , multicenter , r and omized , parallel-group study . Method : Women ( n = 159 ) aged < 65 years experiencing ≥ 20 hot flushes/night sweats per week received either a vaginal ring releasing estradiol acetate at a rate equivalent to 50 μg/day estradiol plus placebo tablets or oral estradiol 1 mg/day plus a placebo vaginal ring for 24 weeks . For patients with inadequate control of symptoms , the dosage was doubled at 12 weeks . A 24-week , open-label extension of the vaginal ring treatment followed double-blind treatment . Results : The frequency of hot flushes/night sweats was significantly reduced ( p < 0.001 ) in both groups at 12 and 24 weeks from baseline , by 84 % and 94 % for the vaginal ring group and by 73 % and 83 % for the oral group , respectively . The mean intensity of urogenital symptoms decreased from screening to the end of treatment in both groups . The incidence of adverse events was similar for both groups . No clinical ly relevant local effects of the vaginal ring were observed . Conclusions : The vaginal ring relieved both systemic and urogenital symptoms and was well tolerated and accepted . Overall , the efficacy , safety and acceptability of the vaginal ring were comparable with those of oral estradiol therapy
Four trials that were not combined in meta-analyses suggested that extracts with high ( > 30 mg/d ) levels of genistein consistently reduced the frequency of hot flushes .
BACKGROUND Vasomotor symptoms , such as hot flushes and night sweats , are very common during the menopausal transition .
Hormone therapy has traditionally been used as a highly effective treatment , but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments .
Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens-plant-derived chemicals that have estrogenic action .
OBJECTIVES To assess the efficacy , safety and acceptability of food products , extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment , placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms ( such as hot flushes and night sweats ) in perimenopausal and postmenopausal women .