title: Effects of dietary phytoestrogens in postmenopausal women. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. 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. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. Vasomotor Symptom Relief by Soy Isoflavone Extract Tablets in Postmenopausal Women: A Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Study The effects of red clover on quality of life in post-menopausal women The Effect of Dietary Soy Supplementation on Hot Flushes Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study Comparison of Pueraria mirifica 25 and 50 mg for menopausal symptoms 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. Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165] Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. [Efficacy of standardized isoflavones extract (Soyfem) (52-104 mg/24h) in moderate and medium-severe climacteric syndrome]. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. [Possibilities for an individualized approach to the treatment of climacteric symptoms with phytoestrogens]. Effects of standardized phytoestrogen on Taiwanese menopausal women. Dietary soy supplementation and phytoestrogen levels. Vasomotor symptoms among Japanese-American and European-American women living in Hilo, Hawaii Changes in the Use of Postmenopausal Hormone Therapy after the Publication of Clinical Trial Results Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: A randomised, double-blind, placebo-controlled trial Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms. Effects of genistein on the endometrium: ultrasonographic evaluation The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study Soy germ isoflavones improve menopausal symptoms but have no effect on blood lipids in early postmenopausal Chinese women: a randomized placebo-controlled trial Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Effect of pure genistein on bone markers and hot flushes Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study. Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. The effect of a soy-rich diet on urogenital atrophy: a randomized, cross-over trial. Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial New equol supplement for relieving menopausal symptoms: Randomized, placebo-controlled trial of Japanese women Benefits of Soy Isoflavone Therapeutic Regimen on Menopausal Symptoms Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial A natural S-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo-controlled study Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause Design and baseline characteristics of a trial on health effects of soy protein with isoflavones in postmenopausal women. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause women. Postmenopausal Hormone Therapy Increases Risk for Venous Thromboembolic Disease: The Heart and Estrogen/progestin Replacement Study Isoflavone treatment for acute menopausal symptoms Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement. Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7 The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: A randomized, double-blind, placebo-controlled study The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women Exposure of infants to phyto-oestrogens from soy-based infant formula Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. 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 Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: Randomized, controlled, double-blind pilot study Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: A double-blind, randomized, placebo-controlled trial A double-blind randomized study on the effects of red clover isoflavones on the endometrium Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women. The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebo-controlled study. The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study Multiplicity in randomised trials II: subgroup and interim analyses Impact of the women's health initiative trial results on hormone replacement therapy. Comparison of 70 mg and 35 mg isoflavone soya supplement for menopause symptoms. Effect of soy isoflavone supplementation on menopausal quality of life Raloxifene, soy phytoestrogens and endothelial function in postmenopausal women The clinical use of a preparation based on phyto-oestrogens in the treatment of menopausal disorders. Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women Oestrogenic effects of plant foods in postmenopausal women. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial Changes in symptoms, lipid and hormone levels after the administration of a cream with phytoestrogens in the Climacteric--preliminary report. Value of ovarian stromal blood flow velocity measurement after pituitary suppression in the prediction of ovarian responsiveness and outcome of in vitro fertilization treatment. The effect of dietary soy supplementation compared to estrogen and placebo on menopausal symptoms: a randomized controlled trial. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Long-term endometrial and breast safety of a specific, standardized soy extract Modest hormonal effects of soy isoflavones in postmenopausal women. [The effects of phytoestrogen therapy on the endometrium in postmenopausal women]. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. Clinical Effects of a Standardized Soy Extract in Postmenopausal Women: A Pilot Study Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment The effect of Promensil, an isoflavone extract, on menopausal symptoms. Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of vasomotor symptoms in perimenopausal women: Phase II Study. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women A Pilot Study of the Effects of Phytoestrogen Supplementation on Postmenopausal Endometrium Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts. Effects of soy isoflavones on menopausal neurovegetative symptoms. Equol improves menopausal symptoms in Japanese women. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms.
abstract: The aim of this study was to test the hypothesis that increased dietary intake of phytoestrogens reduces the health impact of the menopause .  To test this hypothesis , a double-blind , r and omized , entry-exit , cross-over study was conducted to assess the effects of three dietary manipulations -- soy and linseed diets ( high in phytoestrogens ) and a wheat diet ( low in phytoestrogens ) .  Postmenopausal women were recruited and r and omly assigned to one of the three dietary regimens . Urinary phytoestrogen concentrations , hot flush rate , vaginal smears , bone mineral density and bone mineral content were assessed for two 12-week periods . Comparative analysis showed no significant differences , but , when analyzed separately , groups consuming high phytoestrogen diets had between 10 and 30 times higher urinary excretion of phytoestrogens compared to those consuming the low phytoestrogen diet ( p < 0.01 ) . Study participants consuming soy , linseed and wheat diets had a 22 % ( not significant , n.s . ) , 41 % ( p < 0.009 ) and 51 % ( p < 0.001 ) reduction in hot flush rate ; a 103 % ( p < 0.04 ) , 5.5 % ( n.s . ) and 11 % ( n.s . ) increase in vaginal cytology maturation index ; and a 5.2 % ( p < 0.04 ) , 5.2 % ( n.s . ) and 3.8 % ( n.s . ) increase in bone mineral content , respectively . No changes were detected in bone mineral density . The differential effects of high phytoestrogen dietary manipulations on outcomes may represent tissue-specific responses to isoflavones and lignans contained in soy and linseed , respectively . Whilst health outcome measures were not significantly different between groups , the data obtained from separate analysis suggest that phytoestrogens in soy and linseed may be of use in ameliorating some of the symptoms of menopause . Furthermore , the significant decrease in hot flush rate in the wheat group can not be attributable to phytoestrogens measured in this study . Due to subject variability , larger studies are still needed to evaluate population benefit BACKGROUND Concerns regarding the risk of estrogen replacement have result ed in a significant increase in the use of soy products by menopausal women who , despite the lack of evidence of the efficacy of such products , seek alternatives to menopausal hormone therapy . Our goal was to determine the efficacy of soy isoflavone tablets in preventing bone loss and menopausal symptoms . METHODS The study design was a single-center , r and omized , placebo-controlled , double-blind clinical trial conducted from July 1 , 2004 , through March 31 , 2009 . Women aged 45 to 60 years within 5 years of menopause and with a bone mineral density T score of -2.0 or higher in the lumbar spine or total hip were r and omly assigned , in equal proportions , to receive daily soy isoflavone tablets , 200 mg , or placebo . The primary outcome was changes in bone mineral density in the lumbar spine , total hip , and femoral neck at the 2-year follow-up . Secondary outcomes included changes in menopausal symptoms , vaginal cytologic characteristics , N -telopeptide of type I bone collagen , lipids , and thyroid function . RESULTS After 2 years , no significant differences were found between the participants receiving soy tablets ( n = 122 ) and those receiving placebo ( n = 126 ) regarding changes in bone mineral density in the spine ( -2.0 % and -2.3 % , respectively ) , the total hip ( -1.2 % and -1.4 % , respectively ) , or the femoral neck ( -2.2 % and -2.1 % , respectively ) . A significantly larger proportion of participants in the soy group experienced hot flashes and constipation compared with the control group . No significant differences were found between groups in other outcomes . CONCLUSIONS In this population , the daily administration of tablets containing 200 mg of soy isoflavones for 2 years did not prevent bone loss or menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00076050 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 CONTEXT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a r and omized trial setting . OBJECTIVE To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 16 608 postmenopausal women , who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 ( average follow-up , 5.6 years ) . INTERVENTION One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURE Incident invasive cancer of the ovary and endometrium . RESULTS In 5.6 years of follow-up , there were 32 cases of invasive ovarian cancer , 58 cases of endometrial cancer , 1 case of nonendometrial uterine cancer , 13 cases of cervical cancer , and 7 cases of other gynecologic cancers . The hazard ratio ( HR ) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 ( 95 % confidence interval [ CI ] , 0.77 - 3.24 ) . The HR for endometrial cancer was 0.81 ( 95 % CI , 0.48 - 1.36 ) . No appreciable differences were found in the distributions of tumor histology , stage , or grade for either cancer site . The incidence of other gynecologic cancers was low and did not differ by r and omization assignment . More women taking estrogen plus progestin required endometrial biopsies ( 33 % vs 6 % ; P<.001 ) . CONCLUSIONS This r and omized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo . The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen . These data provide additional support for caution in the use of continuous combined hormones Objective : To determine the safety and efficacy of an oral soy isoflavone extract for relief of  menopausal hot flushes . Design : This was a double‐blind , r and omized , parallel group , outpatient , multicenter ( 15 sites ) study . A total of 177 postmenopausal women ( mean age = 55 years ) who were experiencing five or more hot flushes per day were r and omized to receive either soy isoflavone extract ( total of 50 mg genistin and daidzin per day ) or placebo . Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion . Body weight , symptoms , and safety were evaluated at all visits . Results : Relief of vasomotor symptoms was observed in both groups . Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group , whereas the placebo group experienced no relief for the first 4 weeks . Differences between evaluable subjects in both groups were statistically significant over 6 weeks ( p = 0.03 ) . Over 12 weeks , between‐group differences approached significance ( p = 0.08 ) . Endometrial thickness evaluated by ultrasound , lipoproteins , bone markers , sex hormone‐binding globulin and follicle‐stimulating hormone , and vaginal cytology did not change in either group . Conclusions : Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium . Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes . ( Menopause 2000;7:236‐242 . © 2000 , The North American Menopause Society . Background : Due to symptoms and its complications , menopause influences the mental , psychological and physical health , social performance and familial relationships . Because of the undesirable side effects of hormone replacement therapy , tendency and desire toward alternative treatments in relieving menopausal symptoms have increased . Among the alternative therapies are herbs and among those , herbs with phytoestrogens are more preferable . Red clover is a rich source of phytoestrogens . The present study investigated the effect of red clover on quality of life in post-menopausal women . Material s and Methods : In a r and omized , triple-blind , placebo-controlled clinical trial , 72 menopausal women who at least obtained 15 scores in Kupperman Menopausal Index , after two weeks of monitoring , were r and omly allocated to receive either placebo or 45 mg of red clover isoflavones for eight weeks . Before the treatment and at the end of the study , menopause-specific quality of life question naire ( MENQOL ) was completed in the two groups . Findings : A total of 55 women completed the study , 28 subjects in red clover and 27 in placebo group . Mean score of total quality of life ( p < 0.001 in both groups ) , mean score of quality of life in vasomotor domain ( p < 0.001 in both groups ) , psycho-social domain ( p < 0.001 in red clover and p = 0.02 in placebo group ) and physical domain ( p < 0.001 red clover and p = 0.01 placebo group ) significantly reduced compared to the baseline values . However , the differences between two groups were significant neither for total quality of life nor for its domains . Red clover had no side effects and all the subjects in the red clover group were satisfied with the prescribed administration Conclusions : In the present study , the effect of red clover supplementation on menopausal women 's quality of life showed no difference with the placebo . Further clinical trials are recommended Objective To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in post-menopausal women . Methods We carried out a double-blind , parallel , multi-center , r and omized  placebo-controlled trial of 104 post-menopausal women . Fifty-one patients ( age range 48–61 years ) took 60 g of isolated soy protein daily and 53 patients ( age range 45–62 years ) took 60 g of placebo ( casein ) daily . The study lasted 12 weeks . Using analysis of covariance , we analyzed changes from baseline in mean number of moderate to severe hot flushes ( including night sweats ) during treatment . Results Soy was significantly superior to placebo ( P < .01 in reducing the mean number of hot flushes per 24 hours after 4 , 8 , and 12 weeks of treatment . In particular , women taking soy had a 26 % reduction in the mean number of hot flushes by week 3 and a 33 % reduction by week 4 ( P < .001 by the Wilcoxon exact test ) . By the end of the 12th week , patients taking soy had a 45 % reduction in their daily hot flushes versus a 30 % reduction obtained with the placebo ( P < .01 ) . The overall rates of adverse effects were similar for soy and casein-placebo .  Twenty-five patients dropped out of the study : 11 in the soy group and 14 in the  placebo group . Gastrointestinal side effects were the most common cause of premature withdrawal from the study ( seven patients in each group ) . Conclusion Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women 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 Purpose To compare Pueraria mirifica 25 and 50 mg dosages to relieve menopausal symptoms . Methods A double-blind study was conducted on 52 hysterectomized women with menopausal symptoms who had an indication for hormone therapy . The women were r and omly allocated into two groups receiving either Pueraria mirifica 25 mg tablet ( Arm A ; n = 26 ) or Pueraria mirifica 50 mg ( Arm B ; n = 26 ) for 6 months . Menopausal symptoms , physical examination findings , and laboratory data were recorded at baseline . Symptoms were reevaluated at 3 and 6 months , while physical and laboratory examinations were evaluated at 1 month and at the end of treatment . A modified Green climacteric scale was used to evaluate menopausal symptoms ; a score of ≥15 indicated estrogen deficiency . Results All women completed the study . Mean baseline climacteric scores of women who received 25 and 50 mg were : 24.19 ± 9.11 versus 23.19 ± 7.89 , respectively ( p = 0.674 ) . After 3 and 6 months of treatment , scores were 17.92 ± 10.40 versus 15.35 ± 8.44 ( p = 0.332 ) and 14.08 ± 10.30 versus 12.46 ± 6.38 ( p = 0.500 ) , respectively . No significant side effects were observed with Pueraria mirifica 25 or 50 mg . Conclusions Both dosages of Pueraria mirifica were similarly effective and safe in the treatment of menopausal symptoms 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 Introduction Isoflavones are hypothesized to protect against breast cancer , but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue . Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density . Effects on oestradiol , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed . Methods A total of 205 women ( age range 49–65 years ) with Wolfe P2 or DY mammographic breast patterns were r and omly assigned to receive either a red clover-derived isoflavone tablet ( 26 mg biochanin A , 16 mg formononetin , 1 mg genistein and 0.5 mg daidzein ) or placebo .  Change in mammographic breast density , serum oestradiol , FSH , LH , menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed . Results A total of 177 women completed the trial . Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant . There was a significant interaction between treatment group and oestrogen receptor ( ESR1 ) PvuII polymorphism for the change in estimated percentage breast density ( mean ± st and ard deviation ) : TT isoflavone 1.4 ± 12.3 % and TT placebo -9.6 ± 14.2 % ; CT isoflavone -5.2 ± 12.0 % and CT placebo -2.8 ± 10.3 % ; and CC isoflavone -3.4 ± 9.7 % and CC placebo -1.1 ± 9.5 % . There were no statistically significant treatment effects on oestradiol , FSH , or LH ( assessed only in postmenopausal women ) , or on lymphocyte tyrosine kinase activity . Baseline levels of menopausal symptoms were low , and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms . Conclusion In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density , the isoflavone supplement did not increase mammographic breast density in this population of women . Furthermore , there were no effects on oestradiol , gonadotrophins , lymphocyte tyrosine kinase activity , or menopausal symptoms BACKGROUND Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects . Despite numerous clinical trials of short-term isoflavone supplementation , there is a paucity of data regarding longer-term outcomes and safety . OBJECTIVE Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health . DESIGN A multicenter , r and omized , double-blind , placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women . At baseline and after 1 and 2 y , clinical blood chemistry values were measured and a well-woman examination was conducted , which included a mammogram and a Papanicolaou test . A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids . RESULTS The baseline characteristics of the groups were similar . After 2 y of daily isoflavone exposure , all clinical chemistry values remained within the normal range . The only variable that changed significantly was blood urea nitrogen , which increased significantly after 2 y ( P = 0.048 ) but not after 1 y ( P = 0.343 ) in the supplementation groups . Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations . No significant differences in endometrial thickness or fibroids were observed between the groups . Two serious adverse events were detected ( one case of breast cancer and one case of estrogen receptor-negative endometrial cancer ) , which was less than the expected population rate for these cancers . CONCLUSION Daily supplementation for 2 y with 80 - 120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women . This trial was registered at clinical trials.gov as NCT00665860 Plants contain compounds with oestrogen -- like action called phytoestrogens . Soy contains daidzin , a potent phytoestrogen , and wheat flour contains less potent enterolactones . We aim ed to show in 58 postmenopausal women ( age 54 , range 30 - 70 years ) with at least 14 hot flushes per week , that their daily diet supplemented with soy flour ( n = 28 ) could reduce flushes compared with wheat flour ( n = 30 ) over 12 weeks when r and omised and double blind . Hot flushes significantly decreased in the soy and wheat flour groups ( 40 % and 25 % reduction , respectively < 0.001 for both ) with a significant rapid response in the soy flour group in 6 weeks ( P < 0.001 ) that continued . Menopausal symptom score decreased significantly in both groups ( P < 0.05 ) . Urinary daidzein excretion confirmed compliance . Vaginal cell maturation , plasma lipids and urinary calcium remained unchanged . Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group INTRODUCTION In recent years , considerable attention has been paid to isoflavones and their proprieties to alleviate the climacteric symptoms . The goal of this study was to evaluate the efficacy of st and ardized isoflavones extract ( Soyfem ) in moderate and medium-severe  climacteric syndrome .  MATERIAL AND METHODS 555 postmenopausal women were recruited for the study . Out of this group , 169 women completed the study ( 12-month observation period ) . The patients were classified according to the intensity of climacteric symptoms ( < or = 34 points in Kupperman index ) . 1 or 2 tablets of Soyfem were administered twice a day . RESULTS A regular decrease of Kupperman index value and improvement of life quality were observed in the group of 169 postmenopausal women . We have noted a decrease in the intensity and number of hot flushes , diaphoresis ( p < 0.05 ) , diminished sleep disturbances ( p < 0.05 ) , decreased headache , dizziness , and arthrosis pain . The diminished intensity of tiredness , palpitation and breathlessness have been also observed ( p < 0.05 ) . 80 % of all investigated women noted the regression of paresthesis , 20 % indicated the decreased number of paresthesis ( p < 0.05 ) . Influence of Soyfem on the variability and moderation of depressive mood ( p < 0.05 ) have been also positive evaluated by patients . CONCLUSIONS Administration of Soyfem in the dosage 52 to 104 mg/24 hours ( 2 times daily 1 or 2 tablets ) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index . Administration of Soyfem is connected with a good compliance and correlated with well-being in the investigated women allowing a long-term administration OBJECTIVE To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol , a daidzein metabolite . METHOD A r and omized , double-blind , placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women . After taking take 135 mg of isoflavones daily for 1 week , the women in the study group were assigned to the equol-producing ( EP ) or the non-EP group according to the presence or absence of equol in their urine . Menopausal symptoms were evaluated using a modified Kupperman Index . RESULT Compared with the placebo group , the scores for hot flashes and excessive sweating were significantly reduced after 3 months , and the scores for weakness , palpitations , limb paresthesia , and total symptoms after 6 months , in the EP group only . CONCLUSIONS Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol UNLABELLED In climacteric women with contraindications and fear or lack of compliance for taking hormonal replacement therapy  as well as in those cases where risks exceed benefits , the use of phytoestrogens is appropriate having in mind their especially good effect on neurovegetative symptoms . AIM The present r and omized prospect i ve study is aim ed at estimating the possibility for ameliorating climacteric symptoms with  Melbrosia  and at assessment of its effect on different symptoms in order to individualize the therapeutical approach . PATIENTS AND METHODS Two groups of women with climacteric complaints were followed-up -- control group ( n = 32 ) and  treatment group ( n = 34 ) . Climateric symptoms were assessed in the beginning and at the end of the study using Kupperman menopausal index . The levels of FSH , LH , oestradiol as well as some parameters of lipid metabolism were determined . RESULTS A significant decrease of Kupperman index was observed in Melbrosia treatment group in contrast to the control group . No significant changes in gonadotropins , oestradiol and lipid parameters were found in both groups . CONCLUSION The preparation Melbrosia , consisting of phytoestrogens and amino acids exerts a good therapeutic effect on climacteric symptoms mainly on the nervousness , anxiety , irritability , headache , and hot flashes OBJECTIVE To investigate the effects of st and ardized soy extract on climacteric symptoms , lipid profiles , bone markers , and serum isoflavone concentration in healthy Taiwanese postmenopausal women . MATERIAL S AND METHODS A multicenter , open-labeled , r and omized , prospect i ve , comparative study design was used . A total of 130 out patients who had undergone natural menopause were r and omly administered either 70 mg or 35 mg soy extract daily for 24 weeks . RESULTS The evidence suggests that the soy extract treatment that was administered to both groups for 1 month could help reduce climacteric scores ( reductions of 19.66 % [ p<0.01 ] and 18.85 % [ p<0.01 ] in the 35 mg and 70 mg groups compared with baseline , respectively ) , and the efficacy was more potent after 6 months of treatment . Soy isoflavone significantly reduced the total cholesterol ( reductions of 4.50 % [ p<0.01 ] and 3.06 % [ p<0.05 ] in the 35 mg and 70 mg groups , respectively ) and low density lipoprotein cholesterol levels ( reductions of 4.67 % [ p<0.05 ] and 5.09 % [ p<0.05 ] in the 35 mg and 70 mg groups , respectively ) in patients with total cholesterol > 200 mg/dL after 6 months of treatment . In patients with high bone turnover ( urinary deoxypyridinoline/creatinine > 7.4 nM/mM ) , soy extract treatment reduced the deoxypyridinoline/creatinine level by 10.53 % ( p<0.05 ) and 11.58 % ( p<0.05 ) in the 35 mg and 70 mg groups , respectively . Serum levels of isoflavone increased in both groups after 6 months of treatment . CONCLUSION Soy extract is highly efficacious at relieving menopausal symptoms and demonstrates a positive effect on the cardiovascular system and skeleton 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 Objective : The Hilo Women 's Health Survey  was design ed and administered to gather baseline data on women 's health in Hilo , HI . This r and omized , cross-sectional study allowed for a focus on ethnic differences in symptom reporting . The results presented here focus on hot flash and night sweat experience among Japanese-American and European-American women . Design : Survey packets were mailed to street addresses associated with parcel numbers pulled r and omly from Hilo tax maps . Of the 6,401 survey packets delivered to households , 1,824 question naires were completed and returned . The results reported here are based on 869 women aged 40 to 60 , of whom 249 described themselves to be 100 % Japanese and 203 described themselves to be 100 % European-American . Logistic regression analyses were used to examine whether the relationship between ethnicity and vasomotor symptoms persisted after controlling for other variables . Results : European-American participants were more likely to have ever experienced a hot flash as compared with Japanese-American participants ( 72 % vs 53 % , P < 0.01 ) . During the 2 weeks before the survey , European-American participants were more likely to have experienced hot flashes ( P < 0.05 ) and night sweats ( P < 0.01 ) . In logistic regression analyses , after controlling for age , body mass index , menopause status , level of education , financial comfort , smoking habits , alcohol intake , exercise , use of hormone therapy , and soy intake , European-American women were still significantly more likely to have experienced hot flashes ( odds ratio = 1.858 ) and night sweats ( odds ratio = 2.672 ) . Conclusions : The results , based on self-reporting of menopausal symptoms , indicate that Japanese-American women report fewer hot flashes and night sweats than European-American women . Japanese-American women reported a higher intake of soy , but soy intake was not associated with fewer vasomotor symptoms Context Since 1998 , 2 large trials have drastically changed the evidence for the preventive health benefits of postmenopausal hormone replacement therapy .  However , changes in practice often lag behind changes in evidence . Contribution Among mammography recipients in San Francisco , California , the use of  hormone replacement therapy decreased 1 % per quarter after publication of the Heart and Estrogen/progestin Replacement Study and 18 % per quarter after publication of results from the Women 's Health Initiative ( WHI ) . Reduction in use was unrelated to a woman 's age , hysterectomy status , or race or ethnicity . Implication s The WHI result ed in more dramatic changes in practice than are often associated with changes in evidence . The vigorous media coverage of the WHI may have contributed to rapid changes in practice . The Editors In 1995 , approximately 38 % of postmenopausal women in the United States were taking hormone therapy  ( 1 ) . At that time , several observational studies had suggested that hormone therapy offered women some protection against coronary heart disease and osteoporosis ( 2 - 5 ) . A decision analysis published in 1997 concluded that the benefits of hormone therapy outweighed its risks for nearly all women ( 6 ) . More recently , the results from 2 large r and omized clinical trials , the Heart and Estrogen/progestin Replacement Study ( HERS ) ( 7 ) and the Women 's Health Initiative ( WHI ) , have been published ( 8) . These clinical trials demonstrated that the risks associated with hormone therapy outweigh the benefits for women taking continuous estrogen and progestin regimens . As a result of these trial results , the U.S. Food and Drug Administration required new warning labels for all estrogen products ( 9 ) , and the U.S. Preventive Services Task Force revised its assessment of hormone therapy to recommend against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women ( 10 ) . It is important to underst and whether this new scientific evidence is changing the use of hormone therapy . Of note , the results of the WHI were widely disseminated . Despite this publicity , differential access to new information , varied interpretations of study findings , and individual perceptions of menopausal symptoms and hormone side effects may have result ed in different patterns of use . An underst and ing of how use is changing over time provides important information about the dissemination of clinical trial results to women . We design ed our analysis to examine whether the use of hormone therapy  has changed among postmenopausal women as a result of the publication of the results from HERS and the WHI . We were also interested in examining whether patterns of use differ by patient characteristics . Because HERS examined the outcomes of older women , we hypothesized that there would be earlier and more substantial declines in hormone therapy use among this group . We also expected that there would be variation in use by race or ethnicity because white women may have better access to new information ( 11 ) . Finally , because the WHI study results were specific to women taking continuous estrogen plus progestin , we hypothesized that hormone use would be more stable among women who had had hysterectomies because such women typically take only estrogen and may believe that the findings do not apply to them . Methods Sample The San Francisco Mammography Registry is a population -based registry of women undergoing mammography in San Francisco , California . It is 1 of 7 registries participating in the National Cancer Institute Breast Cancer Surveillance Consortium ( 12 ) . This registry began to prospect ively collect patient data and mammography results in 1995 and currently captures about 90 % of mammography examinations performed in San Francisco . Data from 11 mammography facilities are included in this analysis . Women were eligible for this analysis if they were between the ages of 50 to 74 years , were postmenopausal , did not report a personal history of breast cancer , and underwent screening or diagnostic mammography between January 1997 and 19 May 2003 . Women 55 years of age and older were assumed to be menopausal . Women 50 to 54 years of age were considered to be menopausal if both ovaries had been removed or if they reported that their periods had stopped permanently . For women who had mammography more than once in any calendar year , we included only the first instance of mammography in that year to prevent overrepresentation of women undergoing an evaluation of an abnormal mammogram because this experience may influence use of hormone therapy . Our final sample included 15 1862 mammograms received by 71 219 women . Data At the facilities that participate in the San Francisco Mammography Registry , each woman completes a brief , scannable question naire at the time of mammography . This question naire collects information about current use of hormone therapy  and several personal characteristics , including race or ethnicity ( categorized as white , African American , Latina , Chinese , Filipina , other Asian , other ) , family history of breast cancer ( including mother , sisters , and daughters ) , history of childbirth , whether the woman had undergone a hysterectomy , menopausal status , history of breast biopsy ( including fine-needle aspiration , core biopsy , and surgical biopsy ) . Information about age at the time of mammography , date of mammography , and ZIP code of residence is reported by the facility . Data from the year 2000 U.S. Census was used to assign median income for each woman 's ZIP code of residence as a proxy for socioeconomic status . Variables Our outcome variable for this analysis was the current use of hormone therapy . Date of mammography  was represented as a linear term . Binary variables were created for the publication date s of HERS ( before 19 August 1998 vs. that date or later ) and the publication of the principal findings from the WHI ( before 17 July 2002 vs. that date or later ) . Other independent variables examined were age at the time of mammography  , race or ethnicity , median income of the ZIP code of residence , history of childbirth , family history of breast cancer , history of breast biopsy , and previous hysterectomy . Statistical Analysis Because some of the women in this sample had more than 1 mammogram represented in this data set , which spanned a 7-year period , we conducted a repeated- measures logistic regression to adjust the variance estimates for clustering of hormone therapy use over time for individual women and for the clustering of women within mammography facilities ( 13 ) . Generalized estimating equations were implemented by using the SUDAAN statistical package , version 8.0.0 ( Research Triangle Institute , Research Triangle Park , North Carolina ) assuming an exchangeable correlation matrix . These models included a linear term indicating quarter from January 1997 to the first quarter of 2003 to control for temporal trends ( the last quarter included mammograms through 19 May 2003 ) , the variables specified above to indicate the date s of publication of HERS and the WHI , and an interaction term between each of these publication indicators and the time ( in quarters ) following each of these publications to measure changes in use after the publication of these clinical trials . These models also controlled for the individual characteristics described earlier ( that is , age , race or ethnicity , history of childbirth , family history of breast cancer , history of breast biopsy , previous hysterectomy , median income for the ZIP code of residence ) . To specifically test our hypotheses about differential changes in the use of hormone therapy  for subgroups of women on the basis of age , hysterectomy status , and race or ethnicity , we examined interaction terms to test for effect modification . For the main effects , a P value less than 0.05 was considered statistically significant , and for the interaction terms , a P value less than 0.01 was considered to be statistically significant . The likelihood ratio test compared the null model with the fitted model . Role of the Funding Source This work was supported by a National Cancer Institutefunded Breast Cancer Surveillance Consortium agreement . The funding source did not participate in the design , conduct , or reporting of this analysis or in the decision to su bmi t the manuscript for publication . Results The Table shows the characteristics of the sample for each of the study years . Over the time period of the study , the median age decreased from 61 years to 59 years . The racial and ethnic composition of the sample also changed somewhat across the study years . Fewer women undergoing mammography  in 2003 reported a history of childbirth ( 71.7 % vs. 75.2 % ) or hysterectomy than did women undergoing mammography in 1997 . Conversely , more women reported a family history of breast cancer ( 17.1 % vs. 11.8 % ) or a personal history of a previous breast biopsy or aspiration . The average number of mammograms obtained for each woman in our sample across the 7-year study period was 2.1 ( range , 1 to 7 ) . Table . Description of the Sample ( 151 862 Mammograms ) The Figure shows the unadjusted rates of current hormone therapy use by month for all of the women in the sample . Among menopausal women who had received mammography , we estimated that the average proportion reporting the current use of hormone therapy  was 41 % in 1997 . In 1997 , hormone use was highest among white women ( 52.6 % ) and lowest among African-American women ( 34.1 % ) , Latina women ( 33.9 % ) , Chinese women ( 32.2 % ) , and Filipina women ( 29.6 % ) . In 1997 , hormone use was higher among younger women than older women ( 48.7 % vs. 28.7 % ; P < 0.001 ) and among women who had had a hysterectomy compared with women who had not had a hysterectomy ( 60.0 % vs. 36.4 % ; P < 0.001 ) . Figure . Rates of hormone therapy use among postmenopausal women , 1997 to 2003 HERS WHI The adjusted multivariate model estimates that before the publication of HERS , the use of hormone Background and objectives : The potential of soy isoflavones to interfere with thyroid function has been reported . However , there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women . The present study aim ed to evaluate the effect of isoflavones on thyroid function and autoimmunity , menopausal symptoms , serum follicle stimulating hormone ( FSH ) and estradiol levels in oophorectomised women . Methods : A r and omized , double blind , placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones ( 75 mg/day for 12 wk ) on serum thyroid profile ( free T3 , free T4 , TSH , TBG and anti-TPO antibody titres ) assessed at baseline , 6 and 12 wk after r and omization . Assessment was also done for menopause symptom score ( MSS ) three weekly , and FSH and estradiol levels at baseline and at study completion . Results : There was a significant alteration in free T 3 levels in the group receiving isoflavones ( 4.05 ± 0.36 , 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline , 6 and 12 wk , respectively ; P=0.02 ) . However , the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups . MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones ( 12.47 ± 8.15 , 9.35 ± 5.23 and 9 ± 5.14 at baseline , 9 and 12 wk respectively ; P=0.004 ) with significant improvement in urogenital symptoms  compared to placebo . Isoflavones did not significantly affect other parameters during study period . There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups . Interpretation and conclusions : Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinical ly unimportant 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 AIM The aim of the present study was to assess the efficacy and safety of a st and ardized compound based on an extract of soy phytoestrogens , with high doses of isoflavones in the management of  menopausal hot flushes . METHODS A total of 180 women aged 40 - 65 years with a minimum of five moderate-to-severe hot flushes in the last 7 days at baseline and absence of menstruation for at least 6 months participated in a 12-week prospect i ve , r and omized , double-blind , placebo-controlled multicenter trial . After a 2-week run-in period , women received one tablet a day of 80 mg isoflavones ( corresponding to 60 mg of genistein ) or a matching placebo . RESULTS The mean daily number of moderate-to-severe hot flushes decreased in both study groups , but the reduction was greater in the isoflavones arm at 6 ( 36.2 % ) and 12 weeks ( 41.2 % ) than in the placebo arm ( 24.0 % at 6 weeks , 29.3 % at 12 weeks ) , with a difference of 1.1 ( 95 % CI [ -2.0 to -0.06 ] ) ( P = 0.038 ) at 6 weeks and 1.1 ( 95 % CI [ -2.05 to -0.15 ] ) ( P = 0.023 ) at 12 weeks . Similar findings were obtained for hot flushes of any intensity . The Kupperman index decreased in both study groups . Relief of hot flushes was greater when time to menopause was > or=12 months and in cases of BMI > or=27 kg/m(2 ) . CONCLUSION In daily practice conditions , high doses of isoflavones , particularly genistein , can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile The aim of our study was to evaluate the effects of isoflavones on climacteric-related symptoms and on the endometrium in postmenopausal women , in a prospect i ve , open , r and omized , clinical trial performed at the Menopause Clinic of our Department . Seventy postmenopausal women were r and omly assigned to two treatment groups receiving 12 cycles of treatment with genistein ( group A ) or calcium ( group B ) . In all patients ultrasonographic endometrial thickness and Kupperman Index ( KI ) were evaluated at baseline and after 6 and 12 cycles of treatment . At baseline no significant difference was detected in endometrial thickness and in KI between groups A and B. After 6 and 12 cycles of treatment , no significant difference was observed in endometrial thickness between or within groups . Endometrial thickness was lower than 5 mm in all cases before and during treatment except in two cases in group B and in one case in group A after 12 months . At 6 and 12 months , the KI was significantly ( p < 0.05 ) lower in group A in comparison with baseline values and group B. We conclude that genistein administration reduces climacteric symptoms in postmenopausal women and does not increase endometrial thickness Phytoestrogens are increasingly incorporated into the diet of menopausal women . However , there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women . The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women . One hundred and ninety-nine menopausal women were r and omly assigned to consume 40 g flaxseed/d ( n = 101 ) or wheat germ placebo ( n = 98 ) for 12 months . At baseline and at month 12 , serum levels of lipids , bone mineral density ( BMD ) , and menopausal symptoms were evaluated . Statistical analysis was performed under the intention to treat principle . Flaxseed reduced serum total ( -0.20 + /- 0.51 mmol/liter ; P = 0.012 ) and high-density lipoprotein ( -0.08 + /- 0.24 mmol/liter ; P = 0.031 ) cholesterol concentrations compared with wheat germ placebo .  BMD did not differ significantly between the two arms . Both flaxseed and wheat germ reduced ( P < 0.0001 ) the severity scores of menopausal symptoms , but no statistical difference was found between the two arms . Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable , but not clinical ly significant , effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women Objective : We evaluated and compared the effects of the phytoestrogen genistein , estrogen-progestogen therapy ( EPT ) , and placebo on hot flushes and endometrial thickness in postmenopausal women . Design : Ninety healthy , postmenopausal women , 47 to 57 years of age , were r and omly assigned to receive for 1 year continuous EPT ( n = 30 ; 1 mg 17β-estradiol combined with 0.5 mg norethisterone acetate ) , the phytoestrogen genistein ( n = 30 ; 54 mg/day ) , or placebo ( n = 30 ) . Endometrial safety was evaluated by intravaginal ultrasounds at baseline , 6 and 12 months . Results : By comparison with placebo  , daily flushes reduced significantly by a mean of 22 % ( 95 % CI : −38 to −6.2 ; P < 0.01 ) after 3 months , by a mean of 29 % ( 95 % CI : −45 to −13 ; P < 0.001 ) after 6 months , and by a mean of 24 % ( 95 % CI : −43 to −5 ; P < 0.01 ) after 12 months of genistein treatment . Flush score decreased by a mean of 53 % ( 95 % CI : −79 to −26 ; P < 0.001 ) after 3 months , by a mean of 56 % ( 95 % CI : −83 to −28 ; P < 0.001 ) after 6 months , and by a mean of 54 % ( 95 % CI : −74 to −33 ; P < 0.001 ) after 12 months of EPT , as compared with placebo . No side effect was observed on the uterus of the participants . Conclusions : The present study confirms that genistein might have positive effects on hot flushes without a negative impact on endometrial thickness and suggests a future role of this phytoestrogen as a strategically therapeutic alternative in the management of postmenopausal symptoms OBJECTIVES To examine the efficacy of a hop extract enriched in 8-prenylnaringenin ( 8-PN , the phytoestrogen in hops , Humulus lupulus L. ) on relief of  menopausal discomforts .  METHODS A prospect i ve , r and omized , double-blind , placebo-controlled study over 12 weeks with 67 menopausal women , who were administered a hop extract st and ardized on 8-PN ( 100 or 250 microg ) . The responses were determined by means of a modified Kupperman index ( KI ) and a patients ' question naire . RESULTS All groups , including placebo , showed a significant reduction of the KI both after 6 weeks and after 12 weeks . The hop extract at 100 microg 8-PN was significantly superior to placebo after 6 weeks ( P=0.023 ) but not after 12 weeks ( P=0.086 ) . No dose-response relationship could be established , as the higher dose ( 250 microg ) was less active than the lower dose both after 6 weeks and after 12 weeks . Still , a trend for a more rapid decrease of KI was noticed for both active groups as compared to placebo . In particular , the decrease in hot flush score ( isolated from the KI ) was found significant for both treatment groups after 6 weeks ( P<0.01 ) with respect to placebo . Results of the patients ' question naire were consistent with those of the KI , with the most pronounced effects being observed for the 100-microg treatment . CONCLUSIONS Daily intake of a hop extract , st and ardized on 8-PN as a potent phytoestrogen , exerted favorable effects on vasomotor symptoms and other menopausal discomforts . Hop-derived prenylated flavonoids may provide an attractive addition to the alternative treatments available for relief of hot flushes and other menopausal discomforts Objective : Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women , including decreases in perceived quality of life ( QoL ) . A number of trials with hormone therapy showed beneficial effects of the intervention on parameters of quality of life . However , because of known or suspected serious side-effects of conventional hormone therapy there is a need for alternatives . Design : We conducted a double-blind r and omized placebo-controlled trial with soy protein , containing 52 mg genistein , 41 mg daidzein , and 6 mg glycitein ( aglycone weights ) , or milk protein ( placebo ) daily for 1 year . For this trial , we recruited 202 postmenopausal women aged 60 to 75 years . Results : At baseline and at final visit , participants filled in the Short Form of 36 questions ( SF-36 ) , the Question naire on Life Satisfaction Modules ( QLSM ) , and the Geriatric Depression Scale ( GDS ) . For the placebo group scores on all dimensions of the SF-36 and the QLSM decreased during the intervention year , except for the dimension " role limitations caused by physical problems . " The soy group showed increases on two dimensions of the SF-36 ( " social functioning " and " role limitations caused by physical problems " ) and on one dimension of the QLSM . There were however no statistically significant differences in changes of scores between the two intervention groups . For the GDS similarly , no significant differences were found between the groups . Conclusions : In conclusion , the findings in this r and omized trial do not support the presence of a marked effect of soy protein substitution on quality of life ( health status , life satisfaction , and depression ) in elderly postmenopausal women Objective To investigate the effect of an oral soy isoflavone extract ( Phytosoya ) on hot flushes in menopausal women . Design The study was conducted on out patients according to a multicenter , r and omized , double-blind , placebo-controlled  , parallel-group design . A total of 75 patients in natural or surgical menopause suffering from at least seven hot flushes per day were r and omized to receive during 4 months either soy isoflavone extract ( total of 70 mg genistin and daidzin per day ) or placebo . Results There is evidence to suggest that 16 weeks of treatment with soy extract can help reduce the mean number of hot flushes per 24 hours in menopausal women . Withdrawals during this trial made it difficult to obtain an unbiased estimate of the true treatment effect , but numerous sensitivity analyses lend support to the suggestion that taking soy extract can be beneficial in the treatment of hot flushes . In particular , women taking soy extract had a 38 % reduction in the mean number of hot flushes by week 4 and a 51 % reduction by week 8 . By the end of week 16 , patients taking soy extract had a 61 % reduction in their daily hot flushes versus a 21 % reduction obtained with the placebo . “ Responders ” ( defined as patients whose hot flushes were reduced by at least 50 % at the end of treatment period ) were 65.8 % in the soy extract group and 34.2 % in the placebo group ( p < 0.005 ) . ConclusionS oy isoflavone extract may help to reduce the frequency of hot flushes in climacteric women and provides an attractive addition to the choices available for relief of hot flushes Objective Estrogen therapy is , to date , the most effective treatment of menopausal syndrome and also has a favorable effect on lipid profiles . Because of its potential adverse effects , however , a more acceptable alternative therapy needs to be identified . This study examines the effect of soy germ isoflavones on menopausal symptoms and serum lipids . Methods Ninety early postmenopausal Chinese women , aged 45 to 60 years , were r and omly assigned to three treatment groups ( 30 each ) receiving daily doses of 0 ( placebo ) , 84 , and 126 mg of soy germ isoflavones .  Hot flush frequency , Kupperman scores , serum 17&bgr;-estradiol , follicle-stimulating hormone , luteinizing hormone , and serum lipids , including triglyceride , total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , apolipoprotein A-I , and apolipoprotein B100 , were assessed at baseline and at 12 and 24 weeks after treatment . Results Both the frequency of hot flushes and the Kupperman index score decreased in all three treatment groups during the intervention period , but the percentage decreases in both were significantly greater in the two isoflavone groups ( 44.3 ± 19.1 and 57.8 ± 37.4 [ 84 mg isoflavones ] ; 48.5 ± 27.2 and 56.7 ± 26.7 [ 126 mg isoflavones ] ) than in the placebo group ( 27.8 ± 15.5 and 34.6 ± 46.2 ; p < 0.01 ) . There was no significant difference in the changes in estradiol , follicle-stimulating hormone , and luteinizing hormone among the three treatment groups during the study , and no significant differences were observed in the lipid components . Conclusions A daily supplement of 84 or 126 mg soy germ isoflavones may improve menopausal symptoms , although neither dose was found to affect lipid profiles in early postmenopausal Chinese women after 24 weeks of treatment . The favorable effects are unlikely to be associated with female hormones OBJECTIVE To determine the effect of soy-derived isoflavones on hot flushes , endometrial thickness , and the vascular reactivity of uterine and cerebral arteries . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Healthy volunteers in an academic research environment . PATIENT(S ) Sixty-two postmenopausal women aged 45 - 60 years attending the Outpatient Menopause Clinic of our gynecological departments . INTERVENTION(S ) The patients were administered 72 mg of soy-derived isoflavones or placebo under double-blind conditions . The daily number of hot flushes was recorded in a diary . Endometrial thickness was measured by means of transvaginal ultrasound ; the uterine , internal carotid , and middle cerebral arteries were evaluated using Doppler ultrasound . MAIN OUTCOME MEASURE(S ) The daily number of hot flushes , endometrial thickness , and arterial pulsatility index ( PI ) . RESULT ( S ) Both treatments led to a 40 % reduction in the number of hot flushes . Soy-derived isoflavones had no effect on endometrial thickness or the PI of the uterine and cerebral arteries . CONCLUSION ( S ) The daily administration of 72 mg of soy-derived isoflavones is no more effective than placebo in reducing hot flushes in postmenopausal women . It also has no effect on endometrial thickness or the PI of the uterine and cerebral arteries Objective To evaluate the effect of 90 mg of daily genistein on markers of bone turnover and menopausal symptoms .  Design This was a cross-over , placebo-controlled study involving 100 postmenopausal women . Subjects were r and omly assigned to daily genistein or placebo for 6 weeks and crossed over to the alternative preparation for the following 6 weeks . Pure genistein was processed and encapsulated in accordance with British Pharmacopoeia st and ards . Each capsule contained 90 mg of pure genistein while the placebo contained just the eccipients . Results In women with significant hot flushes ( score ( intensity × number ) ≥ 9 ) , genistein reduced symptoms by 30 % compared to baseline and the difference compared to placebo was statistically significant . No effect was observed on biochemical markers of bone turnover , possibly due to the short duration of each arm of the study . Genistein reduced osteocalcin , a marker of bone formation , by 3.6 % compared to baseline and 0.31 % compared to placebo ( p = 0.81 and 0.40 , respectively ) . Genistein increased cross-link telopeptide , a marker of bone resorption , by 1.8 % compared to baseline and 0.29 % compared to placebo ; both differences were not statistically significant ( p = 0.078 and 0.88 , respectively ) . Conclusion Pure genistein at a dose of 90 mg per day appears to reduce the number of hot flushes  in postmenopausal women but the effect is mild CONTEXT The timing of initiation of hormone therapy may influence its effect on  cardiovascular disease .  OBJECTIVE To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began . DESIGN , SETTING , AND PARTICIPANTS Secondary analysis of the Women 's Health Initiative ( WHI ) r and omized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were r and omized to conjugated equine estrogens ( CEE ) or placebo and  16,608 postmenopausal women who had not had a hysterectomy  were r and omized to CEE plus medroxyprogesterone acetate ( CEE + MPA ) or placebo .  Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998 . MAIN OUTCOME MEASURES Statistical test for trend of the effect of hormone therapy on coronary heart disease ( CHD ) and stroke across categories of age and years since menopause in the combined trials . RESULTS In the combined trials , there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [ corrected ] cases of CHD and 239 cases of stroke in the placebo group . For women with less than 10 years since menopause began , the hazard ratio ( HR ) for CHD was 0.76 ( 95 % confidence interval [ CI ] , 0.50 - 1.16 ) ; 10 to 19 years , 1.10 ( 95 % CI , 0.84 - 1.45 ) ; and 20 or more years , 1.28 ( 95 % CI , 1.03 - 1.58 ) ( P for trend = .02 ) . The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years ; for women 10 to 19 years since menopause began , 4 per 10,000 person-years ; and for women 20 or more years from menopause onset , 17 per 10,000 person-years . For the age group of 50 to 59 years , the HR for CHD was 0.93 ( 95 % CI , 0.65 - 1.33 ) and the absolute excess risk was -2 per 10,000 person-years ; 60 to 69 years , 0.98 ( 95 % CI , 0.79 - 1.21 ) and -1 per 10,000 person-years ; and 70 to 79 years , 1.26 ( 95 % CI , 1.00 - 1.59 ) and 19 per 10,000 person-years ( P for trend = .16 ) . Hormone therapy increased the risk of stroke ( HR , 1.32 ; 95 % CI , 1.12 - 1.56 ) . Risk did not vary significantly by age or time since menopause . There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50 - 59 years ; 1.05 for 60 - 69 years , and 1.14 for 70 - 79 years ; P for trend = .06 ) . CONCLUSIONS Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause , but this trend test did not meet our criterion for statistical significance . A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause . These data should be considered in regard to the short-term treatment of menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 Objective Pueraria lobata ( PL ) is used as a traditional Chinese herbal remedy for menopausal symptoms , as well as an ingredient in preparations for conditions affecting menopausal women , such as osteoporosis , coronary heart disease , and some hormone-dependent cancers . The scientific basis for its action may be its action as a phytoestrogen . Design To examine the effects of PL in comparison with hormone replacement therapy ( HRT ) on lipid profile , sex hormone levels , bone turnover markers , and indices of cognitive function . For the study , 127 community-living , postmenopausal women aged 50 to 65 years were r and omized to receive HRT ( n = 43 ) , PL ( equivalent to 100 mg isoflavone ; n = 45 ) , or no treatment ( n = 39 ) for 3 months . The following measurements were carried out at baseline and after 3 months for all participants : menopausal symptoms question naire ; neuropsychological tests covering memory , attention , motor speed , and word-finding ability ; quality of life ( SF36 ) ; lipid profile ; urinary deoxypyridinoline ; dietary phytoestrogen intake and urinary phytoestrogen ; estradiol ; follicle-stimulating hormone ; and luteinizing hormone . Results Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group . No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls . However , both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment . HRT and PL had different effects on cognitive function ;  HRT improved delayed recall , whereas flexible thinking seemed improved in the PL group . Conclusions This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general . However , the effect of PL on cognitive function deserves further study OBJECTIVE To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women . DESIGN In this double-blind , r and omized , placebo-controlled study , a total of 80 women ( mean age = 55.1 years ) , who reported 5 or more hot flush episodes per day , were r and omized to receive either 250 mg of st and ardized soy extract ( Glycine max AT ) a total of 100mg/day of isoflavone ( n = 40 ) or placebo ( n = 40 ) . Exclusion criteria included : contra-indication for hormone therapy ( HT ) , chronic gastrointestinal diseases , and users of HT within the preceding 6-months . For 10-months , climacteric symptoms were evaluated using a score card and the menopausal Kupperman index . Compliance and safety were also assessed . At baseline and the end of the study , lipid and hormonal profiles , as well as vaginal , mammographic and ultrasonographic parameters were measured . The t-test , Wilcoxon test and ANOVA were used in the statistical analysis . RESULTS At baseline , the mean number of hot flushes was 9.6 + /- 3.9 per day in the isoflavone group and 10.1+/-4.9 in the placebo group ( p>0.05 ) . After 10 months , there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo ( 3.1 + /- 2.3 and 5.9 + /- 4.3 , respectively ) ( p<0.001 ) . Kupperman index mean values showed a significant reduction in both groups . However , soy isoflavone was significantly superior to placebo , in reducing hot flush severity ( 69.9 % and 33.7 % , respectively ) ( p<0.001 ) . Endometrial thickness , mammography , vaginal cytology , lipids and hormonal profile did not change in both groups . No serious adverse event related to isoflavone treatment was reported . CONCLUSIONS The soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance , providing a safe and effective alternative therapeutic for postmenopausal women We tested the hypothesis that postmenopausal women on a soy-supplemented diet  show estrogenic responses . Ninety-seven postmenopausal women were r and omized to either a group that was provided with soy foods for 4 weeks or a control group that was instructed to eat as usual . Changes in urinary isoflavone concentrations served as a measure of compliance and phytoestrogen dose . Changes in serum FSH , LH , sex hormone binding globulin , and vaginal cytology were measured to assess estrogenic response . The percentage of vaginal superficial cells ( indicative of estrogenicity ) increased for 19 % of those eating the diet compared with 8 % of controls ( P = 0.06 when tested by ordinal logistic regression ) . FSH and LH did not decrease significantly with dietary supplementation as hypothesized , nor did sex hormone binding globulin increase . Little change occurred in endogenous estradiol concentration or body weight during the diet . Women with large increases in urinary isoflavone concentrations were not more likely to show estrogenic responses than were women with more modest increases . On the basis of published estimates of phytoestrogen potency , a 4-week , soy-supplemented diet was expected to have estrogenic effects on the liver and pituitary in postmenopausal women , but estrogenic effects were not seen . At most , there was a small estrogenic effect on vaginal cytology 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 To evaluate the effects of a non-prescription red clover extract ( MF11 RCE , Melbrosin International , Vienna , Austria ) on selected sex hormones and endometrium in postmenopausal women . PATIENTS AND METHODS One-hundred and nine postmenopausal women with an age > or = 40 years were r and omly assigned to one of two groups either two capsules of MF11RCE ( 80 mg isoflavone ) per day for a 90 day period , or placebo of equal design . After a 7 day washout period , medication was crossed-over for another 90 days . RESULTS Combined evaluation demonstrated that supplementation with MF11RCE ( verum ) , in contrast to placebo , significantly increased plasma testosterone levels and decreased endometrial thickness . CONCLUSION MF11RCE exerts a moderate effect on testosterone levels in postmenopausal women , while estradiol levels remained unchanged . The observed reduction of endometrial thickness provides further support for a safe role for isoflavones in terms of endometrial hyperplasia OBJECTIVE To evaluate the effect of a soy-rich diet on urogenital symptoms , vaginal health index , and vaginal cytology in perimenopausal and postmenopausal women . MATERIAL S AND METHODS Thirty-six perimenopausal and postmenopausal women ( mean age 52.5+/-5.1 years ) participated in a r and omized , cross-over trial with two 12-week diet periods and two 4-week washout periods before and between treatments . The study diet consisted of a control diet ( soy-free diet ) and an isocaloric soy-rich diet ( 25 g soy protein in various forms of soy food containing more than 50 mg/day of isoflavones substituted for an equivalent amount of animal protein ) . Subjects were assessed for urogenital symptoms , vaginal health index , vaginal pH and vaginal cytology . The single physician and the single cytopathologist were blinded with regard to onset , period and r and omization number . Statistical analyses were performed using paired t-test or Wilcoxon Signed Ranks Test , significance was set as P<0.05 . RESULTS Good compliance to the diet was shown by the significant elevation of serum levels of daidzein and genistein during the soy-rich diet period . The symptoms of urge incontinence and vaginal dryness had significantly increased after 12-week of soy-free diet . All other urogenital symptoms did not change in both periods . The vaginal health index , the vaginal pH , the karyopyknotic index , and the maturation value were not significantly changed in both periods . CONCLUSION A soy-rich diet did not relieve the urogenital symptoms or restore the vaginal epithelium or improve the vaginal health in perimenopausal and postmenopausal Thai women Objective : A phase I double-blind clinical trial was conducted to evaluate the effects of a high oral dose of soy isoflavones administered daily for 84 days to healthy postmenopausal women . Principal outcome measures included DNA damage , apoptosis , and changes indicative of estrogenic stimulation . Design : After eligibility and equol-producer status were determined , stratified r and omization was used to assign women to the isoflavone ( active ) or placebo group . Of the 30 women who completed the study , 18 were in the active group . DNA damage was assessed via COMET and apurinic/apyrimidinic site assays in lymphocytes . Apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and activated caspase-3 assays in lymphocytes . Estrogenic/antiestrogenic effects were assessed using a self-report question naire and by assaying for estrogen , follicle-stimulating hormone , luteinizing hormone , and sex hormone-binding globulin in blood . Results : In treated postmenopausal women , there was no indication that high doses of soy isoflavones caused DNA str and breakage , increased apurinic/apyrimidinic sites , or increased apoptosis in peripheral lymphocytes . There were no significant changes in mean values for estrogenic effects or other laboratory measurements . Very few adverse events occurred , and the only drug-related adverse events were mild or grade 1 in severity . Conclusions : Unconjugated soy isoflavones appear to be safe and well tolerated in healthy postmenopausal women at doses of 900 mg/day Objectives : Equol , a metabolite of the isoflavone daidzein , is hypothesized to play a major role in the health benefits of soy . We examined the effect of a new S-equol supplement on  menopausal symptoms and mood states . Design : We conducted a r and omized , double-blind , placebo-controlled trial with our new equol supplement for 12 weeks with 134 Japanese women ( aged 40 - 59 years ) . They were r and omly assigned to three groups : placebo ( n = 44 ) , 10 mg of equol per day ( EQ-1 ; n = 44 ) , and 10 mg of equol three times per day ( EQ-3 ; n = 46 ) . Habitual isoflavone intake was limited to 20 mg/d . Participants completed menopausal symptom and Profile of Mood States question naires at baseline and postintervention . Physical examination and blood and 24-hour urine collection were performed at baseline and postintervention . Results : At baseline , total menopausal symptom score varied by menopausal and equol producer status ( 34.3 % producers ) . A total of 127 participants ( 94.8 % ) completed the trial . No adverse effects were reported , except for a systemic rash in one EQ-3 woman . The anxiety scores of equol producers were lower than those of nonproducers ( P < 0.05 ) . Significant differences between premenopausal and perimenopausal/postmenopausal symptom scores were observed for anxiety , somatic , and total scores . After the EQ-3 intervention , perimenopausal/postmenopausal equol nonproducers showed significant decreases from baseline in all menopausal symptom scores except depression ( P < 0.01 ) . Compared with placebo , the EQ-3 group showed significant decreases in depression scores ( P < 0.05 ) , as well as significant decreases in Tension-Anxiety ( P < 0.05 ) , Depression-Dejection ( P < 0.05 ) and Fatigue ( P < 0.01 ) and increases in Vigor ( P < 0.05 ) of the Profile of Mood States . Conclusion : S-equol supplement improved mood-related symptoms in perimenopausal/postmenopausal equol nonproducers OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women . METHODS In this double‐blind , placebo‐controlled study , 80 women were r and omly assigned to isoflavone ( n = 40 ) and placebo ( n = 40 ) treatment . The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment . Cardiovascular risk factors were assessed by evaluating plasma lipid levels , body mass index , blood pressure , and glucose levels in the participants . To examine the effects of this regime on endogenous hormone levels , follicle‐stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , and 17β‐estradiol  were measured . Transvaginal sonography was performed to quantify endometrial thickness . RESULTS The data showed a decrease in menopausal symptoms ( P < .01 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . Total cholesterol and low‐density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group ( P < .001 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . The isoflavone treatment appeared to have no effect on blood pressure , plasma glucose , and high‐density lipoprotein and triglyceride levels . CONCLUSION This study suggests that isoflavone 100‐mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD OBJECTIVE The objective of this clinical trial was to examine the efficacy of a supplement containing natural S-(-)equol , a daidzein metabolite , in reducing  menopausal symptoms . METHODS In this multicenter , double-blind placebo-controlled trial , 160 equol nonproducing , postmenopausal Japanese women who experienced at least 1 hot flush/day were r and omly assigned to consume 10 mg/day S-(-)equol ( n=77 women )  or placebo ( n=83 women ) for 12 weeks . Participants completed a st and ardized menopausal symptom checklist and rated five common menopause symptoms by a visual analog scale at baseline , week 12 , and week 18 ( 6-week postintervention ) . Physical , blood , and urine examinations were conducted . One hundred twenty-six women completed the study . RESULTS At baseline , daily hot flush frequency was 2.9±2.1 for the S-(-)equol group and 3.2±2.4 for the placebo group . After the 12-week intervention , the S-(-)equol group had a greater decrease from baseline in hot flush frequency compared with the placebo group ( -1.9±1.8/day , -58.7 % , vs. -1.0±2.0/day , -34.5 % , p=0.009 ) . The severity of hot flushes and neck or shoulder muscle stiffness significantly decreased in the S-(-)equol group compared with the placebo group . No changes in clinical parameters or serious adverse effects were reported . CONCLUSIONS This is the first trial to show beneficial effects of a 10-mg natural S-(-)equol supplement consumed daily for 12 weeks on major menopausal symptoms , specifically , hot flushes and neck or shoulder muscle stiffness , in postmenopausal Japanese women . This supplement offers a promising alternative for management of menopausal symptoms Objective : To evaluate in a 24-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 and vagina . Methods : A total of 389 participants met the parent 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 experience hot flushes , and the evaluation was performed in a subgroup of 236 participants ( genistein , n = 119 ; placebo , n = 117 ) . Reductions from the 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 vasomotor symptoms between groups at the 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 ) . After 12 months of genistein therapy , there was a significant reduction ( −56.4 % ) in the mean number of hot flushes , with a significant difference compared with the control group . After 24 months , there was no further decrease in the number of hot flushes in both groups . No significant difference was found in mean endometrial thickness and the maturation value score between the two groups , either at the baseline or after 24 months . Conclusions : The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on the endometrium and vagina , but after the first year , there was no further improvement in the decrease in hot flushes OBJECTIVE To investigate the efficacy-safety balance of the isopropanolic extract of Actaea ( = Cimicifuga ) racemosa ( iCR , Remifemin ) in comparison with tibolone in Chinese women with climacteric complaints . METHOD The r and omized , double-blind , controlled 3-month study in 5 centers of 3 cities in China enrolled 244 menopausal patients aged 40 - 60 years and with a Kupperman Menopause Index (KMI)>or=15 . The participants were assigned to either iCR corresponding to 40 mg crude drug/day ( N=122 ) or tibolone 2.5mg/day ( N=122 ) orally . The primary endpoint was the combination of the Mann-Whitney values ( MWV ) of the KMI and the frequency of adverse events ( benefit-risk balance ) at end of treatment ( MWV>0.5 shows superiority ; MWV>0.36 shows non-inferiority ) . RESULTS KMI decreased from 24.7+/-6.1 to 11.2+/-6.2 and 7.7+/-5.8 ( iCR ) and to 11.2+/-7.2 and 7.5+/-6.8 ( tibolone ) at 4 and 12 weeks . This remarkable and clinical ly relevant improvement was similar in both treatment groups ( MWV=0.47 ; 95 % CI=0.39 - 0.54 ; p(non-inferiority)=0.002 ) showing statistical significant non-inferiority of iCR to tibolone . The KMI-responder rate was similar in both groups ( 84 % and 85 % ) . The safety evaluation showed for both groups a good safety and tolerability profile , however , there is a significant lower incidence of adverse events ( p<0.0001 ) in favor of the herbal treatment . None of the postmenopausal iCR patients experienced vaginal bleeding in contrast to tibolone ( 17 cases ) . Breast and abdominal pain as well as leukorrhea was mostly observed in the tibolone group ( p=0.015 , p=0.008 , p=0.002 ) . No serious adverse event was observed in the iCR-group , however , two occurred in the tibolone-group . The benefit-risk balance for iCR was significantly ( p=0.01 ) superior to tibolone ( MWV=0.56 ; 95 % confidence interval [ 0.51 - 0.62 ] ) . CONCLUSION The efficacy of iCR ( medicinal product Remifemin ) is as good as tibolone for the treatment of climacteric complaints , even for moderate to severe symptoms , whereby iCR is clearly superior regarding the safety profile . This iCR containing medicinal product is an excellent option for treatment of climacteric complaints which has now for the first time been verified in Asian women Objective : To compare the effects of daily ingestion of soy flour ( S ) , ground flaxseed ( F ) , or wheat flour ( W ) muffins , on quality of life and hot flash frequency and severity in postmenopausal women . Design : This was a double-blind , r and omized , controlled , intention-to-treat trial . Ninety-nine women , 1 to 8 years after menopause , ingested muffins with 25 g of flaxseed ( 50 mg of lignans ) , 25 g of soy ( 42 mg of isoflavones ) , or wheat ( control ) daily for 16 weeks . Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries . Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly . Results : Eighty-seven women ( 28 , ground flaxseed muffins ; 31 , soy flour muffins ; and 28 , wheat flour muffins ) completed the trial . Multivariate analysis of variance of all quality -of-life domains yielded an insignificant treatment × time interaction ( F46,122 = 0.92 , P = 0.62 ) but a significant time main effect ( P < .0001 ) . Repeated- measures analyses of covariance controlling for body mass index showed no significant group × time interaction nor time nor group differences on all quality -of-life domains and hot flash measures except severity . Hot flashes were less severe with flaxseed ( P = 0.001 ) compared to placebo ; however , the group × by time interaction was not significant . Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination . Conclusion : Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study This study is a double-blind , r and omized , placebo-controlled trial to assess the effects of high amounts of phytoestrogens on bone mineral density , cardiovascular diseases , cognitive function , performance in activities of daily life and well being .  Participants were healthy postmenopausal women , aged 60 - 75 years . Between March and September 2000 , 202 women were recruited , and , after completion of the baseline measurements , r and omized to either soy protein , containing 99 mg naturally occurring isoflavones or placebo ( milk protein ) daily for 1 year . Analysis of the endpoints will be based on the difference between baseline measurements and measurements at the end of the intervention period with group allocation as independent variable OBJECTIVE To investigate the effect of soy protein supplementation with known levels of phytoestrogens on cardiovascular disease risk factors and menopausal symptoms in perimenopausal women . METHODS A r and omized , double-blind crossover trial was conducted in 51 women consuming isocaloric supplements containing 20 g of complex carbohydrates ( comparison diet ) , 20 g of soy protein containing 34 mg of phytoestrogens given in a single dose , and 20 g of soy protein containing 34 mg of phytoestrogens split into two doses .  Women were r and omly assigned to one of the three diets for 6-week periods and subsequently were r and omized to the remaining two interventions to determine whether differences existed between the treatment diets for cardiovascular disease risk factors , menopausal symptoms , adherence , and potential adverse effects . RESULTS Significant declines in total cholesterol ( 6 % lower ) and low density lipoprotein cholesterol ( 7 % lower ) were observed in both soy diets compared with the carbohydrate placebo diet . A significant decline in diastolic blood pressure ( 5 mm Hg lower ) was noted in the twice-daily soy diet , compared with the placebo diet . Although nonsignificant effects were noted for a number of measures of quality of life , a significant improvement was observed for the severity of vasomotor symptoms and for hypoestrogenic symptoms in the twice-daily group compared with the placebo group . No significant effects were noted for triglycerides , high density lipoprotein cholesterol or frequency of menopausal symptoms . Adherence was excellent in all groups . CONCLUSIONS Soy supplementation in the diet of nonhypercholesterolemic , nonhypertensive , perimenopausal women result ed in significant improvements in lipid and lipoprotein levels , blood pressure , and perceived severity of vasomotor symptoms . These data corroborate the potential importance of soy supplementation in reducing chronic disease risk in Western population OBJECTIVE To evaluate the effects of treatment with Trifolium pratense on climacteric symptoms and sexual satisfaction in postmenopausal women . METHODS This is a prospect i ve , r and omized , double-blind , placebo-controlled study . Initially , 120 women aged 45 - 65 years with menopausal symptoms , more than 12-month amenorrhea and no treatment in the past six months were selected . The participants were then divided into two groups : TG – receiving 40 mg Trifolium pratense , 1 capsule/day ; PG – receiving placebo capsules containing lactose ( control ) , 1 capsule/day . The duration of treatment was 12 months . The patients underwent clinical and laboratory evaluation before treatment and at four , eight and 12 months of treatment . The Kupperman Menopausal Index and the Golombok Rust Inventory of Sexual Satisfaction ( GRISS ) were used . At the end of the study , each group comprised 50 patients . RESULTS According to the Kupperman Menopausal Index , there was significant improvement in menopausal symptoms after four months of treatment , especially in relation to hot flashes , when compared to baseline data in both groups . However , no significant differences were observed between groups . There was no improvement in sexual satisfaction after treatment . CONCLUSION A 12-month treatment with a daily dose of 40 mg Trifolium pratense did not yield a significant improvement in menopausal symptoms and sexual satisfaction Venous thromboembolism , including thrombosis of the deep veins of the legs and embolism to the pulmonary arteries , is a serious and potentially fatal event . Venous thromboembolism is uncommon in the general population , occurring in about 1 to 4 per 1000 adults annually ( 1 , 2 ) . However , the risk is increased in persons with previous venous thromboembolism ( 3 ) , recent surgical procedures ( 4 , 5 ) , immobilization , fracture of a lower extremity ( 4 , 6 , 7 ) , cancer ( 4 , 6 , 7 ) , and inherited coagulation disorders ( 8 , 9 ) . Use of oral contraceptive pills increases risk for venous thromboembolism ( 1 , 2 ) . This increased risk is thought to be due to estrogen and to be dose related ( 3 , 4 ) . The biological potency of the estrogens generally used in postmenopausal hormone therapy is about one-fourth to one-fifth that of the estrogens in modern oral contraceptives . Until recently , there has been little evidence that low-dose estrogen therapy is associated with increased risk for venous thromboembolism ( 5 - 8 ) . Recent observational studies have suggested that postmenopausal hormone therapy causes a twofold to fourfold increase in risk for idiopathic deep venous thrombosis and pulmonary embolism ( 9 - 13 ) . However , these findings may be biased if women taking estrogen are more likely to be evaluated for nonspecific symptoms suggestive of venous thromboembolism . The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized , blinded , placebo-controlled trial of the effect of daily conjugated equine estrogen , 0.625 mg , plus medroxyprogesterone acetate , 2.5 mg , on the rate of new coronary events in 2763 postmenopausal women with established coronary heart disease ( 14 ) . One of the specified secondary outcomes of this trial was venous thromboembolism . An increased risk for venous thromboembolism among women assigned to hormone therapy was noted by the HERS Data and Safety Monitoring Board . The Board instructed the HERS investigators to inform participants and the scientific community of this risk and to institute measures to reduce risk . At a mean follow-up of 3.3 years , the HERS investigators notified participants to discontinue study medication in situations associated with increased risk for venous thromboembolism , such as surgery , hospitalization , fracture , and cancer , and published a letter noting the increased risk ( 15 ) . This report presents the full analysis of the findings . Methods Participants in HERS were postmenopausal women younger than 80 years of age who had coronary disease ( myocardial infa rct ion , coronary artery bypass surgery , percutaneous coronary revascularization , or angiographic evidence of at least 50 % narrowing of one or more major coronary arteries ) and had not had a hysterectomy . Women were excluded if their coronary event occurred within 6 months of r and omization ; they had used hormone therapy within 3 months of r and omization ; they had a history or baseline findings suggestive of venous thromboembolism , breast cancer , or endometrial cancer ; or they had uncontrolled hypertension , diabetes , or other life-threatening diseases ( 16 ) . The protocol was approved by the institutional review board at each of the 20 HERS clinical centers , and all participants provided written informed consent . Participants were r and omly assigned to take one tablet daily of conjugated equine estrogen , 0.625 mg , plus medroxyprogesterone acetate , 2.5 mg , or placebo that was identical in appearance . R and omization was stratified by clinical center and performed in blocks of 4 . To prevent unblinding of clinical center staff , HERS participants reported breast discomfort and vaginal bleeding directly to gynecology staff , who were located separately from the clinical center staff , did not communicate with clinical center personnel about breast or gynecologic problems , and did not participate in ascertainment of outcomes . Follow-up visits to the clinical centers occurred at 4-month intervals . Coronary events ( nonfatal myocardial infa rct ion and coronary death ) were the primary outcome of the trial ( 14 ) . At each visit , clinic staff asked participants if they had been told by a physician that they had a blood clot in the legs or lungs . Women were also asked whether they had been hospitalized , and records were review ed to determine whether venous thromboembolism had occurred . Women were not routinely asked about symptoms of venous thrombosis , such as lower-extremity edema . Diagnosis of deep venous thrombosis required documentation of thrombosis of the popliteal or more proximal veins of the legs by venography , impedance plethysmography , or sonography . Pulmonary embolism required documentation by a nuclear lung scan that suggested a high probability of pulmonary embolism ( segmental or larger perfusion defect with ventilation mismatch ) or by pulmonary angiography that revealed a constant intraluminal filling defect on multiple films . Suspected venous thromboembolism was adjudicated independently and without knowledge of treatment assignment by two physicians at the HERS Coordinating Center , located at the University of California , San Francisco ; disagreements were resolved by consensus . Persons who analyzed data were also blinded to participants ' treatment status . Data were collected on events that occurred during the trial that might be predictors of venous thromboembolism , including fractures , nonfatal myocardial infa rct ion , congestive heart failure , stroke , and transient ischemic attack ( 16 ) . Venous thromboembolism was classified as idiopathic in women who did not have concomitant cancer , nonfatal myocardial infa rct ion , congestive heart failure , or stroke and did not have a fracture , inpatient surgery , or hospitalization in the 3 months before the venous thromboembolic event . In the primary analysis , an unadjusted Cox proportional-hazards model for time to first event was used to compare the rate of venous thromboembolism among women assigned to  hormone therapy with the rate among women assigned to placebo . The primary analysis was intention-to-treat ; participants were categorized according to treatment assignment regardless of compliance . Participants who were lost to follow-up ( 33 women in the hormone therapy group and 36 in the placebo group ) were censored at the last date at which they were known to be alive without venous thromboembolism ; vital status was known for all women at the end of the trial . We also performed an as-treated analysis , in which inclusion in the risk sets was limited to women in both treatment groups whose average compliance with therapy during the trial ( measured by pill count ) was at least 80 % . Relative hazards were also estimated by year since r and omization ( women with events in earlier years were censored ) , and continuous trend in the log relative hazard was examined in a companion model . We repeated the main analyses separately for idiopathic and nonidiopathic venous thromboembolism . Potential risk factors for venous thromboembolism were first examined by using univariate proportional hazards models adjusted for treatment assignment . In these models , postr and omization events and medication use were represented by time-dependent indicators , which reverted to zero 90 days after fracture , surgery , or hospitalization or when therapy was discontinued . Variables associated with venous thromboembolism for which the associated P value was less than 0.2 in univariate analyses were considered for inclusion in multivariate models and retained in the model if the P value remained less than 0.2 . Statistical analyses were performed by using SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Results The 20 HERS centers enrolled 2763 women between February 1993 and September 1994 ; of these , 1380 were assigned to the hormone therapy group and 1383 to the placebo group . Participants ranged in age from 44 to 79 years ( mean age [ SD ] , 67 7 years ) . At baseline , the treatment groups did not differ significantly ( Table 1 ) . Table 1 . Baseline Characteristics of HERS Participants At the end of the first year , 82 % of women in the hormone therapy group and 91 % in the placebo group reported taking study medication ; by the end of the third year , these proportions had decreased to 75 % and 81 % , respectively . Cumulative incidence curves for all venous thromboembolic events ( deep venous thrombosis and pulmonary embolism ) are shown in the Figure . During 10 985 woman-years of follow-up , 47 women experienced a  venous thromboembolic event : 34 in the hormone-treated group ( 6.2 per 1000 woman-years ) and 13 in the placebo group ( 2.3 per 1000 woman-years ) ( relative hazard , 2.7 [ 95 % CI , 1.4 to 5.0 ] [ P = 0.003 ] ; excess risk , 3.9 per 1000 woman-years [ CI , 1.4 to 6.4 per 1000 woman-years ] ; number needed to treat for harm , 256 [ CI , 157 to 692 ] ) . The relative hazard of venous thromboembolism did not differ significantly among the 20 clinical centers . Figure . Kaplan-Meier estimates of the cumulative incidence of venous thromboembolic events ( top ) , deep venous thrombosis ( middle ) , and pulmonary embolism ( bottom ) . More women in the hormone therapy group than in the placebo group experienced deep venous thrombosis ( 25 compared with 9 ; relative hazard , 2.8 [ CI , 1.3 to 6.0 ] ; P = 0.008 ) and pulmonary embolism ( 11 compared with 4 ; relative hazard , 2.8 [ CI , 0.9 to 8.7 ] ; P = 0.08 ) ( Table 2 ) . Two women , both in the hormone therapy group , died of pulmonary embolism . The relative hazard was increased for idiopathic ( relative hazard , 3.1 [ CI , 0.8 to 11.3 ] ) and nonidiopathic venous thromboembolic events ( relative hazard , 2.5 [ CI , 1.2 to 5.3 ] ) . The overall results were unchanged in an as-treated analysis that was limited to women who reported taking more than 80 % of their assigned study medication ( relative hazard , 3.2 [ CI , 1.5 to 6.9 ] ; P = 0.003 ) . Table 2 . Venous Thrombolic Events by Treatment Group and Year of R and omization Table 2 shows relative hazards for venous thromboembolism by year since r and omization . The number of episodes of pulmonary 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 OBJECTIVES To investigate the effect on hot flushes of a soy isoflavone extract alone ( Study A ) and with the addition of a supplement of polyunsaturated fatty acids , PUFAs ( Study B ) . METHODS Subjects were postmenopausal women ( 29 in Study A , 28 in Study B ) with more than five troublesome hot flushes per day . Both studies were double-blind r and omized placebo-controlled trials with cross-over design , of 24-week duration . After a 2-week observation period , they were r and omized to receive two capsules per day providing 60 mg of isoflavones or placebo for 12 weeks ; thereafter , women who had taken isoflavones were given placebo for a second 12-week period , and vice-versa . Women in the Study B were given also two capsules per day containing a PUFA supplement for the entire 24-week test period . RESULTS Both studies showed the isoflavone extract to have no greater efficacy on hot flushes than the placebo . During the 24 weeks of the Study B there was a progressive and highly significant reduction in the number of hot flushes , independent of whether the women had begun with isoflavones or with placebo . CONCLUSION In these two trials the isoflavone extract did not show greater efficacy on the hot flushes than the placebo . The reduction of hot flushes observed in the Study B might be due to the PUFA supplement . PUFAs , particularly Omega ( Omega ) 3-fatty acids , could reduce hot flushes through their influence on neuronal membranes and /or the modulation of the neurotransmitter function and the serotoninergic system . Studies specifically design ed to document the action of PUFAs on hot flushes would be welcome We previously reported that a high soya diet improved memory and frontal lobe function in young volunteers , and since soya isoflavones are agonists at oestrogen receptors , they may improve these functions in postmenopausal women . Thirty-three postmenopausal women ( 50 - 65 years ) not receiving conventional hormone replacement therapy ( HRT ) were r and omly allocated in a double-blind parallel study to receive a soya supplement ( 60 mg total isoflavone equivalents/day ) or placebo for 12 weeks . They received a battery of cognitive tests and completed analogue rating scales of mood and sleepiness , and a menopausal symptoms question naire before the start of treatment and then after 12 weeks of treatment . Those receiving the isoflavone supplement showed significantly greater improvements in recall of pictures and in a sustained attention task . The groups did not differ in their ability to learn rules , but the isoflavone supplement group showed significantly greater improvements in learning rule reversals . They also showed significantly greater improvement in a planning task . There was no effect of treatment on menopausal symptoms , self-ratings of mood , bodily symptoms or sleepiness . Thus , significant cognitive improvements in postmenopausal women can be gained from 12 weeks of consumption of a supplement containing soya isoflavones that are independent of any changes in menopausal symptoms , mood or sleepiness Objective Preliminary data suggest that flaxseed , a rich source of dietary lignans , may be a potentially effective treatment of hot flashes . A phase III , r and omized , placebo , controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes . Methods Postmenopausal women with or without breast cancer were r and omly assigned to a flaxseed bar ( providing 410 mg of lignans ) for 6 weeks versus a placebo bar . Participants completed daily , prospect i ve , hot flash diaries during the baseline week , and then ate one study bar per day for 6 weeks while recording their daily hot flashes . The intraparticipant difference in hot flash activity between baseline and the last treatment week was the primary endpoint . Adverse effects were evaluated through a self-report and the Common Terminology Criteria assessment . Results A total of 188 women were enrolled in this trial . The mean hot flash score was reduced 4.9 in the flaxseed group and 3.5 in the placebo group ( P = 0.29 ) . In both groups , slightly more than a third of the women received a 50 % reduction in their hot flash score . Only one adverse effect was significantly different between groups , grade 1 pruritus , which was more common in the placebo group ( 8 % vs 1 % ) . Both groups reported abdominal distension , flatulence , diarrhea , and nausea . Adherence and ability to detect treatment assignment did not differ between groups . Conclusions The results of this trial do not support the use of 410 mg of lignans for the reduction of hot flashes . The bars were fairly well tolerated , with both groups reporting gastrointestinal effects , probably due to the fiber content Background . The unexpected results of the Women 's Health Initiative study have decreased the use of conventional hormone therapy ( HT ) , changing physicians ' and patients ' attitudes towards HT and increasing their interest in alternative options . Objective . The present study aim ed to evaluate the effect of isoflavones contained in red clover extracts ( Trifolium pratense ) on menopausal symptoms , lipids and vaginal cytology in menopausal women . Methods . Sixty postmenopausal women aged > 40 years , non-users of HT , with Kupperman index score ⩾15 , were double-blindly r and omized to receive either a commercially available red clover isoflavone supplement ( 80 mg/day ) or placebo for 90 days . Subsequently , after a 7-day washout period , subjects switched to receive the opposite treatment for a further 90 days . Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline , 90 and 180 days . Results . Fifty-three women ( 88.3 % ) completed the trial . Mean age was 51.3 ± 3.5 years , 69.7 % of the women were aged 50 years or more . There was no significant effect on body mass index , weight or blood pressure after either treatment phase . Baseline Kupperman index score decreased significantly after each treatment phase , with the decrease more pronounced after the isoflavone phase ( baseline : 27.2 ± 7.7 ; after isoflavone : 5.9 ± 3.9 ; after placebo : 20.9 ± 5.3 , p < 0.05 ) . Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic , cornification and basal cell maturation indices . Mean total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels also decreased ; however , only the latter was significantly lower compared with placebo . Conclusions . Compared with placebo , red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels 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 BACKGROUND The isoflavones genistein , daidzein , and their glycosides , found in high concentrations in soybeans and soy-protein foods , may have beneficial effects in the prevention or treatment of many hormone-dependent diseases . Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities , it has been suggested that adverse effects may occur in infants fed soy-based formulas . METHODS To evaluate the extent of infant exposure to phyto-oestrogens from  soy formula  , the isoflavone composition of 25 r and omly selected sample s from five major br and s of commercially available soy-based infant formulas were analysed , and the plasma concentrations of genistein and daidzein , and the intestinally derived metabolite , equol , were compared in 4-month-old infants fed exclusively soy-based infant formula ( n = 7 ) , cow-milk formula ( n = 7 ) , or human breast-milk ( n = 7 ) . FINDINGS All of the soy formulas contained mainly glycosides of genistein and daidzein , and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture . From the concentrations of isoflavones in these formulas ( means 32 - 47 micrograms/mL ) , the typical daily volume of milk consumed , and average bodyweight , a 4-month-old infant fed soy formula would be exposed to 28 - 47 per day , or about 4.5 - 8.0 mg/kg bodyweight per day , of total isoflavones . Mean ( SD ) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 ( 443 ) ng/mL and 295 ( 60 ) ng/mL , respectively , which was significantly greater ( p < 0.05 ) than in the infants fed either cow-milk formulas ( 3.2 [ 0.7 ] and 2.1 [ 0.3 ] ng/mL ) , or human breast-milk ( 2.8 [ 0.7 ] and 1.4 [ 0.1 ] ng/mL ) , and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods . INTERPRETATION The daily exposure of infants to isoflavones in soy infant-formulas is 6 - 11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods . Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000 - 22000 times higher than plasma oestradiol concentrations in early life , and may be sufficient to exert biological effects , whereas the contribution of isoflavones from breast-milk and cow-milk is negligible OBJECTIVE To test the hypothesis that increasing the intake of isoflavones by dietary supplementation may produce a therapeutic effect in reducing the incidence and severity of hot flushes in menopausal women . METHODS Fifty-one postmenopausal women were r and omized to placebo and active ( one tablet per day of a 40-mg isoflavone supplement ) groups in a cross-over design trial . After a 1-week run-in period , subjects were commenced on a 12-week period of treatment ( active or placebo ) , followed by a 1-month placebo wash-out period , then crossed over to the alternative treatment regimen for a further 14 weeks . Symptom diaries were maintained throughout the trial and at the start and end of treatment . Plasma sex hormone binding globulin ( SHBG ) assay , full blood count , biochemical profiles , vaginal swabs and vaginal ultrasound scans were performed and isoflavones determined in 24-h urine collection s by high-pressure liquid chromatography ( HPLC ) analysis . RESULTS There was no significant difference between active and placebo groups in the reduction in hot flushes between start and finish time-points . Analysis performed on interim data time-points revealed a substantially greater reduction in flushing in the active group than placebo at 4 and 8 weeks after commencement of treatment , but this was not statistically significant . There were no significant differences between groups for Greene scores or in SHBG levels , hematological or biochemical parameters and vaginal swab or ultrasound findings . The combined values for all subjects , regardless of treatment group , revealed a strong negative correlation between the level of urinary isoflavone excretion and the incidence of hot flushes . CONCLUSIONS These data do not indicate a therapeutic benefit from dietary supplementation with isoflavones in women experiencing menopausal symptoms , but do indicate that the apparent placebo effect in many studies of menopausal symptoms may be attributable to dietary sources of isoflavones . The study also demonstrates that 3 months of isoflavone supplementation did not cause adverse events or endometrial changes OBJECTIVE To evaluate the effect of soy isoflavones and melatonin in relieving  menopausal symptoms .  METHODS Double-blind , multicenter , r and omized trial performed according to a 2 x 2 factorial design . Treatment groups : ( 1 ) soy isoflavones+melatonin ; ( 2 ) soy isoflavones alone ; ( 3 ) melatonin alone ; ( 4 ) placebo . 80 mg of soy isoflavones , 3 mg of pure melatonin or placebo were supplemented to participants for 3 months . Severity of menopausal symptoms was recorded at baseline and after 3 months using the Greene Climacteric Scale . RESULTS 388 consecutive women were screened : not eligible 98 , refused informed consent 28 . R and omized 262 and analyzed 232 ; twelve women withdrew because of adverse events .  Median percent differences between basal and final scores were 39 % in the isoflavones + melatonin group , 38 % in the isoflavones alone group , 26 % in the melatonin alone group and 38 % in the placebo group . Placebo response was much higher than planned , making it meaningless to perform any statistical test . With regard to somatic and vasomotor symptoms , outcome was similar among the four groups , whereas improvement of psychological symptoms was higher in the isoflavones+melatonin group than in the other three . CONCLUSIONS Present data do not show any advantage of isoflavones or melatonin over placebo for the relief of menopausal symptoms . However , the effect in psychological symptoms in the isoflavones + melatonin group should be further investigated Objective : The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of  menopausal vasomotor symptoms .  Methods : This study was a r and omized , four-arm , double-blind clinical trial of st and ardized black cohosh , red clover , placebo , and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate ( CEE/MPA ; n = 89 ) . Primary outcome measures were reduction in vasomotor symptoms ( hot flashes and night sweats ) by black cohosh and red clover compared with placebo ; secondary outcomes included safety evaluation , reduction of somatic symptoms , relief of sexual dysfunction , and overall improvement in quality of life . Results : Reductions in number of vasomotor symptoms after a 12-month intervention were as follows : black cohosh ( 34 % ) , red clover ( 57 % ) , placebo ( 63 % ) , and CEE/MPA ( 94 % ) , with only CEE/MPA differing significantly from placebo . Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo . Secondary measures indicated that both botanicals were safe as administered . In general , there were no improvements in other menopausal symptoms . Conclusions : Compared with placebo , black cohosh and red clover did not reduce the number of vasomotor symptoms . Safety monitoring indicated that chemically and biologically st and ardized extracts of black cohosh and red clover were safe during daily administration for 12 months OBJECTIVE To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy ( HRT ) . METHODS This prospect i ve , double-blind and placebo-controlled study included 50 postmenopausal women r and omly divided into two groups : 25 women on soy germ isoflavones ( 60 mg per day , capsules ) and 25 women on placebo .  Inclusion criteria included : non-vegetarian , non-asian women whose last menstruation date d at least 12 months prior to the beginning of the study , with FSH > 40 mIU/ml , hot flushes and contraindication for HRT , not using tamoxifen or antibiotic and no disease of the gastrointestinal tract . For 6 months , the Kupperman menopausal index ( KMI ) , the vaginal cytological maturation value ( MV ) and both hormonal and lipid profiles were assessed . The t-test and analysis of variance ( ANOVA ) were employed to compare the two groups . RESULTS In both groups , a decreased KI rate was observed . However , isoflavone was significantly superior to placebo in reducing hot flushes ( 44 % versus 10 % , respectively ) ( P < 0.05 ) . After 6 months , the isoflavone group showed increased estradiol levels with unchanged FSH , LH , and vaginal cytology , and a reduction of 11.8 % in LDL and an increase of 27.3 % in HDL ( P < 0.05 ) . In the placebo group , just a reduction in MV was observed after 6 months ( P < 0.05 ) . CONCLUSIONS Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile , showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT Objective : To evaluate vaginal , endometrial , and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy ( HT ) . Design : This was a 1-year , r and omized , double-blind , placebo-controlled trial of 351 women , ages 45 to 55 , with two or more vasomotor symptoms per day . Women were r and omly assigned to ( 1 ) black cohosh , ( 2 ) a multibotanical containing black cohosh , ( 3 ) the same multibotanical plus dietary soy counseling , ( 4 ) HT , or ( 5 ) placebo .  Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month . Data on vaginal cytology and dryness were collected ( at baseline and 3 and 12 mo ) . Daily menstrual diaries were maintained by 313 women with a uterus , and abnormal bleeding was evaluated . Serum estradiol , follicle-stimulating hormone , luteinizing hormone , and steroid hormone-binding globulin were assessed ( baseline and 12 mo ) among 133 postmenopausal women . Gynecologic outcomes of the five groups were compared . Results : The five groups did not vary in baseline vaginal cytology profiles , vaginal dryness , menstrual cyclicity , or hormone profiles . The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months ( P < 0.05 ) . Abnormal bleeding occurred in 53 of 313 ( 16.9 % ) women . There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups , whereas women in the HT group had a greater risk than those in the placebo group ( P < 0.001 ) . Among postmenopausal women , HT significantly decreased follicle-stimulating hormone and increased estradiol ; none of the herbal interventions showed significant effects on any outcomes at any time point . Conclusion : Black cohosh , used alone or as part of a multibotanical product with or without soy dietary changes , had no effects on vaginal epithelium , endometrium , or reproductive hormones Objective : To evaluate the effect of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women and to evaluate the safety of Pueraria mirifica on endometrium ; breast tissue ; and hematologic , hepatic , and renal systems . Design : This was a r and omized , double-blind , placebo-controlled study in a university hospital of healthy postmenopausal women aged 45 to 60 years old . Women were enrolled voluntarily and r and omly received 20 , 30 , or 50 mg Pueraria mirifica in capsules or identical placebo once daily for 24 weeks . Outcome measures were lipid profiles , bone-specific alkaline phosphatase level , endometrial thickness , endometrial histology , breast ultrasonography , complete blood count , liver function test , and renal function test . Results : After 24 weeks of treatment , 71 women were evaluated . Of the 71 women , 51 r and omly received varying doses of Pueraria mirifica and 20 received placebo . Pueraria mirifica and placebo significantly increased triglyceride levels by 15 % from baseline levels ( P < 0.05 ) . The Pueraria mirifica group showed a significant decrease in bone-specific alkaline phosphatase levels after 24 weeks of treatment compared with the placebo group ; from 0.22 ± 0.18 U/L to 0.13 ± 0.01 U/L in the Pueraria mirifica group and from 0.20 ± 0.10 U/L to 0.20 ± 0.14 U/L in the placebo group . Endometrial thickness did not change after treatment in both groups ( P > 0.05 ) . No endometrial proliferation or hyperplasia was reported after 24 weeks of treatment in both groups . There were no significant differences in adverse effects on breast tissue , complete blood count , and liver and renal function tests between the Pueraria mirifica and placebo groups in this study . Conclusion : Pueraria mirifica at a dose of 20 , 30 , and 50 mg/d for a 24-week period demonstrated an estrogen-like effect on bone turnover rate . Pueraria mirifica did not demonstrate an estrogen-like effect on endometrial thickness and endometrial histology . Mild adverse effects occurred after Pueraria mirifica and placebo treatment OBJECTIVES To examine the efficacy of a hop extract ( st and ardized at 100mug 8-prenylnaringenin per day ) for relief of  menopausal discomforts .  METHODS A 16-week r and omized , double-blind , placebo-controlled , cross-over study was conducted with 36 menopausal women . The participants were r and omly allocated to either placebo or active treatment ( hop extract ) for a period of eight weeks after which treatments were switched for another eight weeks . The Kupperman Index ( KI ) , the Menopause Rating Scale ( MRS ) and a multifactorial Visual Analogue Scale ( VAS ) were assessed at baseline , and after eight and sixteen weeks . RESULTS After 8 weeks , both active treatment and placebo significantly improved all outcome measures when compared to baseline with somewhat higher average reductions for placebo than for the active treatment . After 16 weeks only the active treatment after placebo further reduced all outcome measures , whereas placebo after active treatment result ed in an increase for all outcome measures . Although , the overall estimates of treatment efficacy ( active treatment-placebo ) based on linear mixed models do not show a significant effect , time-specific estimates of treatment efficacy indicate significant reductions for KI ( P = 0.02 ) and VAS ( P = 0.03 ) and a marginally significant reduction ( P = 0.06 ) for MRS after 16 weeks . CONCLUSIONS Whereas the first treatment period result ed in similar reductions in menopausal discomforts in both treatment groups , results from the second treatment period suggest superiority of the st and ardized hop extract over placebo . Thus , phytoestrogen preparations containing this st and ardized hop extract may provide an interesting alternative to women seeking relief of mild vasomotor symptoms 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 : The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women . Design : This was a r and omized , double-blind , placebo-controlled trial of menopausal women , aged 38 to 60 years , who experienced 4 to 14 hot flashes per day . After a 1-week run-in period , a total of 190 menopausal women were r and omized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks . The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary . The secondary outcomes included changes in quality of life and hormonal profiles . Results : A total of 147 women ( 77 % ) completed the study . It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally . At 8 weeks hot flash frequency was reduced by 43 % in the 40-mg DRI group and by 41 % in the 60-mg DRI group , compared with 32 % in the placebo group ( P = not significant vs placebo ) . The corresponding numbers for 12 weeks were 52 % , 51 % , and 39 % , respectively ( P = 0.07 and 0.09 vs placebo ) . When comparing the two treatment groups with the placebo group , there were significant reductions in mean daily hot flash frequency . The supplement ( either 40 or 60 mg ) reduced hot flash frequency by 43 % at 8 weeks ( P = 0.1 ) and 52 % at 12 weeks ( P = 0.048 ) but did not cause any significant changes in endogenous sex hormones or thyroid hormones . Menopausal quality of life improved in all three groups , although there were no statistically significant differences between groups . Conclusions : DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes OBJECTIVES To investigate the effectiveness and safety of a red clover isoflavone dietary supplement ( Promensil , Novogen Ltd. , Australia ) versus placebo on the change in hot flush frequency in postmenopausal women . METHODS In this r and omized , double blind , placebo-controlled trial 30 women with more than 12 months amenorrhoea and experiencing more than five flushes per day were enrolled . All received single blind placebo tablets for 4 weeks and were subsequently r and omized to either placebo or 80 mg isoflavones for a further 12 weeks . Efficacy was measured by the decrease in number of hot flushes per day and changes in Greene Climacteric Scale Score . RESULTS During the first 4 weeks of placebo the frequency of hot flushes decreased by 16 % . During the subsequent double blind phase , a further , statistically significant decrease of 44 % was seen in isoflavones group ( P<0.01 ) , whereas no further reduction occurred within the placebo group . The Greene score decreased in the active group by 13 % and remained unchanged in the placebo group . CONCLUSION In this study , treatment with 80 mg isoflavones ( Promensil ) per day result ed in a significant reduction in hot flushes from baseline . At the end of the study there was a significant decrease in hot flushes of 44 % between the active and placebo group , demonstrating the effectiveness of Promensil in the management of hot flushes The present study aim ed to evaluate the short-term effects of a combination of isoflavones , lignans and Cimicifuga racemosa on acute climacteric-related symptoms in postmenopausal women in a double-blind , r and omized , placebo-controlled trial performed at the menopause clinic of our department . Eighty healthy postmenopausal women were r and omly assigned to two treatment groups – one receiving the combination ( group A , n = 40 ) , the other receiving calcium supplements ( group B , n = 40 ) – for three cycles of 28 days . Climacteric-related symptoms were evaluated by the Kupperman index ( KI ) at baseline and after the three cycles of treatment . At baseline no significant difference was detected in KI between groups A and B ; however , after three cycles of treatment , KI was significantly ( p < 0.05 ) lower in group A compared with baseline and with group B. We conclude that the administration of a combination of isoflavones , lignans and C. racemosa already reduces acute climacteric symptoms in postmenopausal women after 3 months of treatment . This prompt effect is probably due to the different pharmacokinetic properties of isoflavones and lignans ; isoflavones are absorbed faster than lignans , while lignans are removed later . The combination of these molecules can guarantee a better reduction of postmenopausal symptoms over a 24-h period Objective To assess the effects of a red clover-derived isoflavone extract on the Ki-67 proliferative marker of endometrial biopsies in 45-to 50-year-old perimenopausal women . We hypothesized that we would be able to detect a decrease in the Ki-67 proliferative index during the late follicular phase after a 3-month course of ∼50 mg red clover isoflavones . Isoflavones have been found to have some antiestrogenic effects , and an antiproliferative effect during the perimenopausal period may be especially useful owing to the excessive endometrial proliferation often characteristic of this period . Design In a double-blind , r and omized , controlled study , 30 women between the ages of 45 and 50 years consented to an endometrial biopsy  before and after a 3-month course of either placebo or active isoflavone extract . The biopsies were timed as close as possible to days 7–11 of the menstrual cycle , and simultaneous measurements of transvaginal endometrial thickness , uterine artery Doppler , hormone profiles , lipids , and bone markers were performed . Results Of 30 women , 2 did not return for a second biopsy , and a third had an unsuccessful second biopsy . Four subjects were excluded from the Intention to Treat analysis because they did not have a menstrual bleed within the time frame of the study ( 3 subjects ) or were tested on day 13 instead of between days 7 and 11 of the cycle ( 1 subject ) . There was no change in the Ki-67 proliferation index after treatment in either group . Eight subjects in the placebo group and eight in the P-07 group had proliferative endometrial biopsies that were synchronized with estradiol levels at baseline and post-treatment , and analysis of these subjects revealed no detectable change in the relationship between estradiol levels and Ki-67 with treatment in either group . There was no change in fasting lipids , bone markers , uterine Doppler resistance , or pulsatility index . Conclusion In this small pilot study , we did not find , using immunohistochemical quantification of the Ki-67 antigen , that red clover isoflavones had an antiproliferative effect in the endometrium . Small sample size , examination of a relatively short interval in the menstrual cycle , and isoflavone formulation may have contributed to our lack of findings ; however , we believe that the issue of isoflavones and their possible antiproliferative effect is deserving of further study . A simpler physiological model with less hormonal variability , such as healthy , recently menopausal women on predetermined doses of estrogen , may prove to be more informative OBJECTIVE To determine the effects of soy-derived isoflavones on vaginal epithelium and the endometrium . DESIGN Double-blind , r and omized , placebo-controlled crossover trial . SETTING Outpatient clinic of a university hospital . PATIENT(S ) Sixty-four postmenopausal women with a history of breast cancer . INTERVENTION(S ) The women took ( in a r and omized order ) 114 mg of isolated isoflavonoids or placebo in tablets daily for 3 months ; the treatment regimens were crossed over after a 2-month washout period . The subjects were studied before and on the last day of each treatment period . MAIN OUTCOME MEASURE(S ) Vaginal dryness , maturation index ( MI ) of vaginal epithelium , endometrial thickness , histology , and expression of estrogen ( E ) and progesterone ( P ) receptors and the proliferation marker Ki-67 in the endometrium . RESULT ( S ) Isolated isoflavones did not relieve vaginal dryness . Maturation index values remained unchanged during the isoflavone regimen , but decreased during the placebo regimen . No changes were found in any of the variables measured in the endometrium . CONCLUSION ( S ) Daily administration of 114 mg of isolated isoflavones for 3 months had no effect on the subjective perception of vaginal dryness or on objective findings in the vagina or endometrium . This implies safety with regard to the endometrium OBJECTIVE To evaluate the efficacy of synthetic genistein for reducing the frequency and severity of hot flushes . STUDY DESIGN A 12 week r and omized double-blind , placebo-controlled study in which 84 postmenopausal women received placebo or a single 30 mg dose of synthetic genistein . Outcome measures primary : percentage change in the number of daily hot flushes from pre-treatment to week 12 . Secondary : duration and severity of daily hot flushes , Greene Climacteric Scale score , serum follicle stimulating hormone ( FSH ) , 17β-estradiol and endometrial thickness . RESULTS Genistein supplemented subjects completing at least 4 weeks on trial ( n=40 ) demonstrated a 51 % reduction ( 9.4 - 4.7/day ) in the number of hot flushes by week 12 compared to a 27 % reduction in the placebo group ( 9.9 - 7.1/day ) ( p=0.026 ) . Subjects in the genistein group also reported significantly fewer hot flushes per day ( p=0.010 ) and a decrease in total duration of hot flushes per day ( p=0.009 ) at week 12 versus placebo . Subjects on genistein ( n=32 ) completing 12 weeks on trial demonstrated a 51 % reduction ( 9.7 - 4.7/day ) in the number of hot flushes by week 12 ( p=0.049 ) compared to 30 % reduction in the placebo group ( 9.8 - 7.0/day ) and had fewer hot flushes per day and a decrease in total duration of hot flushes per day at week 12 compared to placebo ( p=0.020 and p=0.017 , respectively ) . There were no differences between groups in Greene Climacteric Scale , FSH , 17β-estradiol , endometrial thickness or adverse events . CONCLUSIONS The current study provides the first evidence that a single daily dose of 30 mg of synthetic genistein reduces hot flush frequency and duration BACKGROUND A traditional asiatic phytoestrogen-rich diet is associated with a lower incidence of estrogen-dependent cancers and clinical consequences of postmenopausal estrogen deficiency . First Wilcox in 1990 , showed an increase of the vaginal cell maturation with phytoestrogens on postmenopausal women , but this has not been confirmed in some subsequent studies . METHODS In this study , we analyzed the effects of a 6-month soy-rich diet on the vaginal epithelium of asymptomatic postmenopausal women in a r and omized clinical trial . 187 women were recruited for the study and divided into three groups : a phytoestrogen rich diet group ; a hormonal replacement group , and a control group . A vaginal sample for hormonal cytology was taken before and at the end of the study , and sent unnamed to a cytologist . RESULTS The karyopycnotic index ( KI ) increased significantly in the diet group and in the HRT group but not in the control group . The maturation value ( MV ) had an identical trend to the KI . CONCLUSION We conclude that a soy rich diet is efficacious in increasing the maturation indices of vaginal cells . This effect could be a useful marker of the efficacy of a dietary intervention with phytoestrogen rich foods , and should be considered during preventive interventions against menopausal effects and vaginal atrophy 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 Subgroup analyses can pose serious multiplicity concerns . By testing enough subgroups , a false-positive result will probably emerge by chance alone . Investigators might undertake many analyses but only report the significant effects , distorting the medical literature . In general , we discourage subgroup analyses . However , if they are necessary , research ers should do statistical tests of interaction , rather than analyse every separate subgroup . Investigators can not avoid interim analyses when data monitoring is indicated . However , repeatedly testing at every interim raises multiplicity concerns , and not accounting for multiplicity escalates the false-positive error . Statistical stopping methods must be used . The O'Brien-Fleming and Peto group sequential stopping methods are easily implemented and preserve the intended alpha level and power . Both adopt stringent criteria ( low nominal p values ) during the interim analyses . Implementing a trial under these stopping rules resembles a conventional trial , with the exception that it can be terminated early should a treatment prove greatly superior . Investigators and readers , however , need to grasp that the estimated treatment effects are prone to exaggeration , a r and om high , with early stopping STUDY OBJECTIVE To describe the impact of the results of the Women 's Health Initiative ( WHI ) on hormone replacement therapy ( HRT )  discontinuation rates . DESIGN Retrospective chart review . SETTING University-based family medicine clinic . SUBJECTS Ninety-eight postmenopausal women ( aged 50 - 79 yrs ) with an intact uterus who were receiving HRT .  MEASUREMENTS AND MAIN RESULTS Two study periods were defined : pre-WHI ( July 9 , 2001-January 9 , 2002 ) and post-WHI ( July 9 , 2002-January 9 , 2003 ) . Patient demographics and HRT discontinuation or persistence data were collected . Seven women were eligible for only for pre-WHI , 13 only for post-WHI , and 78 were eligible for both groups based on HRT use during both time periods . Forty-two of the 78 women were r and omized to the pre-WHI group and 36 to the post-WHI group to yield equal groups of 49 each . No significant demographic differences existed between the groups . Time-to-event analysis revealed an increased probability of HRT discontinuation after WHI versus before WHI ( log-rank test , p<0.01 ) . A subset of 85 women taking HRT 1 year before WHI were followed for 18 months . Discontinuation rates were 8 % ( 7 of 85 patients ) during the 12 months before WHI and 38 % ( 30 of 78 ) during the 6 months after WHI , with 80 % ( 24 of 30 ) of these patients discontinuing within 3 months . CONCLUSION Increased HRT discontinuation was temporally associated with release of WHI data , which implies that highly publicized , negative outcomes data can quickly influence pharmacotherapy decisions Previous studies have reported a 20—30 % reduction of climacteric symptoms with placebo and additional reductions of 10—20 % using soy preparations providing 30—104 mg/day of isoflavones . However most studies were based on data from postmenopausal women . Their hormone status was quite different when compared to women undergoing menopause transition ( MT ) . A single center prospect i ve and r and omized study was conducted to investigate the effect of insoflavone supplements with different doses in climacteric symptoms in women undergoing MT . After initial screening 48 women were recruited and assigned to two groups 35 mg and 70 mg groups with treatment duration of 6 weeks . Isoflavone supplements were prepared from soy extract in 325 mg capsules containing 17.5 mg of isoflavones per capsule ( Phyto Soya Arkopharma Laboratories Pharmaceutique France ) . Modified Greene ’s climacteric scale with three additional symptoms ( frequency incontinence and vaginal dryness ) was used to assess climacteric symptoms . ( excerpt Objective The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women . Methods A multicenter , r and omized , double-blind , placebo-controlled 24-month trial was conducted to assess the effect of 80 or 120 mg of daily aglycone hypocotyl soy isoflavone supplementation on quality of life in 403 postmenopausal women using a vali date d Menopause-Specific Quality of Life question naire . Results Menopause-Specific Quality of Life domain scores at 1 year and 2 years were similar to baseline . There were no differences in domain scores among treatment groups . Conclusions Soy isoflavone supplementation offers no benefit to quality of life in postmenopausal women Objective To compare the effects of raloxifene and soy phytoestrogens on endothelial function in healthy , postmenopausal women . Design R and omized , double-blind , placebo-controlled , cross-over trial . Subjects ( n = 22 ; mean age 58.5 years ) underwent endothelial function testing at baseline and following 6 weeks of daily raloxifene 60 mg , soy phytoestrogens 55 mg , and placebo in r and om sequence with intervening 6-week wash-out periods . Endothelial function was assessed as flow-mediated vasodilatation ( FMD ) of the brachial artery using high-resolution ultrasound ; digital flux was measured with laser Doppler velocimetry . Results Baseline ( pretreatment ) FMD was almost within normal range at 9.6 % ( ±6.4 ) . FMD did not change from baseline within any treatment group , and no between-group differences were detected . FMD values following treatment with raloxifene , soy , and placebo were 10.3 % ( ±12.3 ) , 8.3 % ( ±7.7 ) , and 9.5 % ( ±4.4 ) , respectively . Area under curve ratios showed no treatment differences for digital velocimetry . Conclusions In this study , neither raloxifene nor soy enhanced endothelial function in postmenopausal women . However , the cohort had relatively normal endothelial function at baseline . Further study is required to determine if particular subgroups of postmenopausal women derive vascular benefit from the use of selective estrogen receptor modulators or soy phytoestrogens In order to evaluate the efficacy of soya isoflavones ( genistein and daidzein ) in the treatment of the principal menopausal disorders , a double blind r and omized study was performed on a sample of 50 women ( with an average age of 53.3 + /- 3.1 years ) with Climacteric syndrome referred to the I Clinica Ostetrica e Ginecologica , Policlinico Umberto I , Roma . The research protocol involved the r and om subdivision of the enrolled sample into two groups of 25 women , group 1 ( with an average age of 53.3 + /- 3.5 years , and an average menopausal age of 51.6 + /- 1.8 years ) and group 2 ( with an average age of 53.1 + /- 2.9 years , and an average menopausal age of 51.3 + /- 1.2 years ) , who were to receive treatment for three months with the product being studied and with a placebo . After the three-month period , as an additional check , the group initially treated with the placebo would move to the phyto-oestrogens and viceversa . All of the patients were subjected to a series of clinical and instrumental examinations and were asked to fill in a question naire concerning their complaints , at the start , at halfway ( third month ) and at the end ( sixth month ) of the trial . The results of the evaluation of the question naires performed on the 47 patients who had completed the trial showed , in the first three months , an improvement in the symptoms ( hot flushes ) in 11 patients treated with phyto-oestrogens against 6 patients from the group that received only the placebo . In the second three-month period the hot flushes reappeared in 4 of the 11 patients who had previously seen improvements and had then passed to the placebo . In contrast , the group that passed to the phyto-oestrogens , after treatment with the placebo , experienced the disappearance of hot flushes in 11 women , including the 6 who had already improved in the first three months . There was no significant reduction in anxiety , insomnia or vaginal dryness . None of the enrolled patients indicated complaints linked to the treatment . It can be concluded that the use of a product based on phyto-oestrogens , such as the one experimented , can lead to a significant reduction in some of the disorders linked with the menopause , especially hot flushes The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine ( ISB ) in the treatment of menopausal symptoms and dyslipidaemia .  Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus . Berberine , extracted from the plant Berberis aristata , lowers plasma cholesterol and triglycerides ( TG ) by increasing low-density lipoprotein ( LDL ) receptors and reducing hepatic synthesis of TG . One hundred twenty women with a mean age of 54.8 ± 0.6 years were enrolled and r and omized to treatment with ISB ( estromineral lipid [ EL ] = 60 cases ) or calcium and vitamin D3 ( CaD = 60 cases ) . Menopausal symptoms , plasma cholesterol , and TG were evaluated at baseline , and after 4 and 12 weeks . EL treatment significantly lowered plasma total cholesterol ( −13.5 % ± 0.7 vs −0.2 % ± 0.5 ) , LDL cholesterol ( −12.4 % ± 1.5 vs + 0.8 % ± 0.7 ) and TG ( −18.9 % ± 2.5 vs −1.3 % ± 1.2 ) and improved menopausal symptoms compared with CaD treatment . Safety parameters were unchanged during the study . The combination of berberine and isoflavones was effective in lowering cardiovascular ( CV ) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life Otolaryngol Head Neck Surg 1988;114 : 887 - 90 . 9 Jacobson JT , Morehouse CR . A comparison of auditory brain stem response  and behavioural screening in high risk and normal newborn infants . Ear Hear 1984;5:247 - 53 . 10 Mahoney TM , Eichwald JG . The ups and " downs " of high risk screening : the Utah statewide program . Seminars in Hearing 1987;8:155 - 63 . 11 Stein L , Clark S , Kraus N. The hearing impaired infant : patterns of identification and habilitation . Ear Hear 1983;4:232 - 6 . 12 Elssmann SF , Matkin ND , Sabo MP . Early identification of sensorineural hearing impairment . The HearingJournal 1987;40:13 - 7 . 13 American Speech-Hearing- Language Association . Guidelines for the identification of hearing impairment in at risk infants age birth to 6 months . ASHA 1988;30:61 - 4 . 14 Hendricks-Munoz KD , Walton JP .  Hearing loss in infants with persistent fetal circulation . Pediatrics 1988;81:650 - 6 . 15 Naulty CM , Weiss IP , Herer GR . Progressive sensorineural hearing loss in survivors of persistent fetal circulation . Ear Hear 1986;7:74 - 7 . 16 Hall DMB , ed . Screening for hearing impairment . In : Health for all children . Oxford : Oxford Medical Publications , 1989:59 - 67 Objective : To investigate the efficacy and safety of the special extract ERr 731 from the roots of Rheum rhaponticum compared to placebo in perimenopausal women with climacteric complaints . Design : A multicenter , prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial in which 109 women with climacteric complaints received either one enteric-coated tablet of ERr 731 ( n = 54 ) or placebo ( n = 55 ) daily for 12 weeks . Primary outcome criterion for efficacy was the change in Menopause Rating Scale II ( MRS II ) total score after 12 weeks . Other efficacy assessment s analyzed number and severity of hot flushes , menopause-specific quality of life , number of bleeding/spotting days , and treatment outcome . Results : By 12 weeks , the MRS II total score and each MRS II symptom significantly decreased in the ERr 731 group compared to the placebo group ( P < 0.0001 ) . After 4 weeks , ERr 731 also significantly decreased the number and severity of hot flushes ( P < 0.0001 ) . After 12 weeks , the overall menopause-specific quality of life was significantly better in women treated with ERr 731 compared with placebo ( P < 0.05 ) . Treatment outcome assessed by investigators and participants was better in the ERr 731 group , and ERr 731 was better tolerated than placebo . There were no differences in gynecological findings including endometrial biopsies , bleeding , weight , blood pressure , pulse , and laboratory safety parameters between the treatment groups . No adverse events were classified as being related to the investigational medication . Conclusions : Compared to placebo , ERr 731 significantly reduces the occurrence and severity of climacteric complaints in perimenopause . It is also safe and well tolerated OBJECTIVE To establish the changes in lipid and hormone levels , as well as in symptoms , after topical application of a cream with phytoestrogens in postmenopausal women . METHODS 30 postmenopausal women were studied . At baseline and 1 month after the beginning of treatment , levels of FSH , estradiol , estrone , testosterone , and rostenedione , dehydroepi and rosterone , total cholesterol , HDL-C , LDL-C , and triglycerides were measured . Climacteric symptoms were evaluated with a modified Kupperman 's index ( KI ) . The subjects received a cream with phytoestrogens ( n = 15 ) or placebo ( cold cream ) ( n = 15 ) in a r and omized , double-blind manner . Statistically significant differences were determined by Student 's t test . RESULTS No differences were found in hormones , lipids , or in KI between the groups . When comparing each group separately , only a significant decrease in KI was found , in both groups , at the end of the treatment . CONCLUSIONS This cream with phytoestrogens had an effect only in climacteric symptoms , but similar to the placebo . The lack of effect in the other variables was probably due to the administration route , or to a lack of effect of this product OBJECTIVE To evaluate whether ovarian stromal blood flow velocity after pituitary suppression is predictive of ovarian response and the outcome of IVF treatment in patients with normal basal serum FSH levels and to compare the predictive value of this test with age , early follicular phase serum FSH level , E2 level , and FSH : LH ratio . DESIGN Prospect i ve observational study of women undergoing IVF treatment .  SETTING A tertiary referral center for assisted reproduction . PATIENT(S ) Eighty-eight women who received the long buserelin acetate treatment protocol .  INTERVENTION(S ) Transvaginal color and pulsed Doppler measurement of the ovarian stromal peak systolic velocity ( PSV ) after pituitary suppression and measurement of the basal serum FSH level , E2 level , and FSH : LH ratio .  MAIN OUTCOME MEASURE(S ) Number of mature oocytes retrieved and pregnancy rate . RESULT ( S ) Ovarian stromal PSV was the most important single independent predictor of ovarian response in patients with a normal basal serum FSH level , when compared with age , basal FSH level , E2 level , or FSH : LH ratio . Patients in group 2 ( PSV > or = 10 cm/s ) had a significantly higher median number of mature oocytes retrieved ( 11 versus 5.5 ) and a higher clinical pregnancy rate ( 35.3 % versus 11.3 % ) than patients in group 1 ( PSV < 10 cm/s ) , even after controlling for age . CONCLUSION ( S ) Ovarian stromal blood flow velocity , after pituitary suppression is confirmed , is predictive of ovarian responsiveness and the outcome of IVF treatment OBJECTIVES To compare the effects of daily ingestion of dietary soy supplementation , low-dose hormone therapy ( HT ) and placebo on psychological , somatic and urogenital symptoms in postmenopausal women . STUDY DESIGN A double-blind , r and omized , controlled trial . Sixty healthy , symptomatic , postmenopausal women of 40 - 60 years of age were allocated to use dietary soy supplementation ( containing 90 mg of isoflavone ) or HT ( 1 mg estradiol and 0.5 mg norethisterone acetate ) or placebo . MAIN OUTCOME MEASURES the Menopause Rating Scale ( MRS ) was used to assess menopausal symptoms at baseline and after 16 weeks of treatment . Intention-to-treat analyses were performed using the chi-square test , Fisher 's exact test , the Kruskal-Wallis non-parametric test and analysis of variance ( ANOVA ) . RESULTS No statistically significant differences were found between the groups with respect to baseline clinical and sociodemographic characteristics . The psychological , somatic and urogenital symptoms analyzed in the MRS improved during treatment in all the groups , except for urogenital symptoms in the placebo group in which no significant changes were detected . Comparison between groups revealed a statistically significant improvement in somatic symptoms ( hot flashes and muscle pain ) in the users of HT ( -45.6 % ) and dietary soy supplementation ( -49.8 % ) . Urogenital symptoms ( vaginal dryness ) improved significantly in HT users ( -38.6 % ) and in users of the dietary soy supplementation ( -31.2 % ) . There was no statistically significant difference between the groups with respect to overall MRS score or to scores obtained in the psychological symptoms subscale . CONCLUSION Dietary soy supplementation may constitute an effective alternative therapy for somatic and urogenital symptoms of the menopause OBJECTIVE The aim of this study was to evaluate the effects of isoflavone on the climacteric symptoms ( Kupperman Menopausal index ) , vaginal pH , vaginal cytology ( vaginal maturation index ) and endometrium ( evaluated by ultrasound and biopsy ) in postmenopausal women . METHODS It was a single-center , 6-month , r and omized , double-blind , estrogen-controlled trial . Seventy-nine women were r and omly assigned to one of the two treatment groups : isoflavone ( n=40 ) : 300 mg of the st and ardized soy extract with a medium dose of 120 mg isoflavones/day as glycoside and aglycone ( 60 mg twice a day ) , or estrogen ( n=39 ) : one capsule of 0.625 mg conjugated equine estrogens and other capsule with glucose 0.625 mg ( placebo ) . RESULTS After treatment , there was a decrease in the symptomatology in both estrogen and isoflavone groups . There was a significant decrease in vaginal pH , an increase in superficial vaginal cells and endometrium proliferation after 3 and 6 months of treatment in the estrogen group , but no differences were observed in the isoflavone group for these variables . CONCLUSIONS We concluded that the daily st and ardized soy extract with 120 mg isoflavones ' effect on symptoms was similar to that from estrogen . Soy isoflavone has no effect on endometrium and vaginal mucosa during the treatment Objective To assess the effects of an oral soy isoflavone extract ( Phytosoya ® ) on endometrium and breast in postmenopausal women treated for 3 years . Methods A total of 395 postmenopausal women were included in this international prospect i ve , open-label study . The number of patients who completed the 3-year study was 197 . The women were treated for 3 years with a specific , st and ardized soy isoflavone extract ( total 70 mg/day ) .  Endometrial biopsy , transvaginal ultrasonography and mammography  were performed before and after 3 years of treatment . Results No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years . Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies . The endometrial safety of this extract has been demonstrated ( point estimate 0.5 % ) . There was no statistically significant change in endometrial thickness after 3 years ( 98.4 % inactive or atrophic and 0.3 % proliferative endometrium at 1 year ) . Mammography results showed no notable change from baseline . No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment . The global safety was rated as either ‘ excellent ’ or ‘ good ’ by 99.1 % of investigators and 99.0 % of patients after 3 years of treatment . The adverse events were as follows : eight patients had metrorrhagia and seven patients had at least one breast adverse event : three patients had ‘ breast pain ’ , two patients reported ‘ breast tenderness ’ and two patients had ‘ hypertrophic breast ’ ( most of them were possibly treatment-related ) . Conclusions As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years , the endometrial safety of this extract has been demonstrated . Furthermore , as demonstrated by the lack of change in endometrial thickness associated with the histologic results , we suggest that this extract does not exert a mitogenic effect on the endometrium . These results suggest that daily administration of 70 mg of a specific , st and ardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast Soy isoflavones have been hypothesized to exert hormonal effects in postmenopausal women . To test this hypothesis , we studied the effects of three soy powders containing different levels of isoflavones in 18 postmenopausal women .  Isoflavones were consumed relative to bodyweight [ control : 0.11 + /- 0.01 ; low isoflavone ( low-iso ) : 1.00 + /- 0.01 ; high isoflavone ( high-iso ) : 2.00 + /- 0.02 mg/kg/day ] for 93 days each in a r and omized crossover design . Blood was collected on day 1 of the study ( baseline ) and days 36 - 38 , 64 - 66 , and 92 - 94 of each diet period , for analysis of estrogens , and rogens , gonadotropins , sex hormone binding globulin ( SHBG ) , prolactin , insulin , cortisol , and thyroid hormones . Vaginal cytology specimens were obtained at baseline and at the end of each diet period , and endometrial biopsies were performed at baseline and at the end of the high-iso diet period , to provide additional measures of estrogen action . Overall , compared with the control diet , the effects of the low-iso and high-iso diets were modest in degree . The high-iso diet result ed in a small but significant decrease in estrone-sulfate ( E1-S ) , a trend toward lower estradiol ( E2 ) and estrone ( E1 ) , and a small but significant increase in SHBG . For the other hormones , the few significant changes noted were also small and probably not of physiological importance . There were no significant effects of the low-iso or high-iso diets on vaginal cytology or endometrial biopsy results . These data suggest that effects of isoflavones on plasma hormones per se are not significant mechanisms by which soy consumption may exert estrogen-like effects in postmenopausal women . These data also show that neither isoflavones nor soy exert clinical ly important estrogenic effects on vaginal epithelium or endometrium 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 PURPOSE Hot flashes represent a significant clinical problem for some breast cancer survivors . Safe , effective treatment is needed for this prominent clinical problem . Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem , there are continued safety concerns regarding the use of hormonal therapies in these women . Based on anecdotal information , we hypothesized that soy-derived phytoestrogens , weak estrogen-like substances in the soybean that demonstrate estrogen agonist and /or antagonist effects when they bind to estrogen receptors , could alleviate hot flashes . This current trial was design ed to investigate this hypothesis . PATIENTS AND METHODS This double-blind clinical trial involved breast cancer survivors with substantial hot flashes . After r and omization , patients underwent a 1-week baseline period with no therapy . This was followed by 4 weeks of either soy tablets or placebo . The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks . Patients completed a daily question naire documenting hot flash frequency , intensity , and perceived side effects . RESULTS Of the 177 women who were r and omized and started the study substance , 155 ( 88 % ) provided useable data over the first 5 weeks ; 149 provided usable data over the entire 9 weeks . There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo . At study completion , patients preferred the soy product 33 % of the time , the placebo 37 % of the time , and neither substance 31 % of the time . No toxicity was observed . CONCLUSION The soy product did not alleviate hot flashes in breast cancer survivors BACKGROUND S-equol , a metabolite of the soy isoflavone daidzein , has been proposed as having potential for relief of menopausal symptoms . This study compared the efficacy of the natural S-equol supplement , SE5-OH , with isoflavones for relieving hot flashes and other menopausal symptoms . METHODS An 8-week r and omized , double-blind , active comparator trial with SE5-OH was conducted in postmenopausal women ( aged 45 - 65 years ) , who experienced ≥5 hot flashes/day . Participants ( n=102 ) were assigned to one of four treatment groups : 10 ( n=24 ) , 20 ( n=27 ) , or 40 ( n=25 ) mg S-equol/day or soy isoflavones ( n=26 ) . Participants recorded their hot flash frequency and rated their menopause symptom severity . RESULTS Reductions in hot flash frequency at week 8 were similar for all treatment groups . However , based on analyses of the cumulative effect for the 8-week period , 40 mg/day S-equol had a greater reduction of hot flash frequency compared to isoflavones ( p=0.021 ) . A subgroup analysis further indicated that for subjects with > 8 hot flashes/day at baseline , 20 and 40 mg/day S-equol were superior to isoflavones in reducing hot flash frequency ( p=0.045 and p=0.001 , respectively ) . In addition , 10 and 20 mg/day S-equol improved muscle and joint pain score compared with isoflavones ( p=0.003 and p=0.005 , respectively ) . CONCLUSIONS S-equol , 10 mg/day , appears to be as effective as soy isoflavones at reducing hot flash frequency and more effective for relieving muscle and joint pain in postmenopausal women .  S-equol , ≥20 mg/day , alleviates hot flashes to a greater extent than soy isoflavones in those women who experience > 8 hot flashes/day Objective This double‐blind , r and omized study was aim ed at evaluating comparatively , in postmenopausal women , the activity of a st and ardized soy extract ( SOYSELECT ) and placebo when given alone or in combination with conjugated equine estrogens ( CEE ) on early climacteric symptoms . Lipid profile , pituitary hormones , osteocalcin and endothelin levels , and vaginal and endometrial parameters were also evaluated . Design Participants in the control group were given placebo , and participants in the treated group were given 400 mg/day of a st and ardized soy extract , corresponding to 50 mg/daily of isoflavones . After 6 weeks of treatment , CEE was also then given to each participant at a dose of 0.625 mg/day for 4 weeks . At the end of this period , soy and placebo treatment were suspended , and , until the end of the study ( week 12 ) , participants were administered 10 mg/day of medroxyprogesterone acetate in association with CEE ( 0.625 mg/day ) . Results When compared with pretreatment data , on week 6 of the study , a significant ( p < 0.01 ) reduction in the mean number of hot flushes per week was observed in participants who were receiving the st and ardized soy extract , whereas a more marked relief was observed in both soy and placebo groups during CEE administration . Concurrently , the severity of hot flushes , assessed by means of the Greene climacteric scale , was also reduced in the soy group participants ( p < 0.001 , by paired t‐test ) . No soy‐related changes were observed on vaginal cytology , endometrial thickness , uterine artery pulsatility index , or metabolic and hormonal parameters tested . Finally , CEE‐related changes on genital tract , uterine vascular compartment , and pituitary hormones were not modified by soy treatment . Conclusions SOYSELECT may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy . ( Menopause 2000;7:105‐111 . © 2000 , The North American Menopause Society . 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 OBJECTIVES The primary aim was to assess whether the use of an isoflavone extract containing 40 mg or 160 mg of total isoflavones affects the frequency of menopausal flushes and other symptoms . The secondary aims were assessment s of possible effects on menopause symptom scores and biological measures of estrogen activity . METHODS A r and omized , double-blind , placebo-controlled prospect i ve trial of 37 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period . The women were r and omized to three treatment groups : placebo , 40 mg or 160 mg , delivered in tablet form . RESULTS There was no significant difference in the incidence of flushes between the three groups at trial conclusion . There was no difference between the groups in Greene Menopause Symptom Scores , vaginal pH , levels of follicle stimulating hormone ( FSH ) , sex hormone binding globulin ( SHBG ) or total cholesterol , liver function or blood parameters . A statistically significant increase in high-density lipoprotein ( HDL ) cholesterol of 18.1 % ( p = 0.038 ) occurred in the 40-mg group . CONCLUSION A large placebo response and inadvertent use of dietary isoflavones in the placebo group may have obscured a significant change in flushing frequency . Previous uncontrolled studies cl aim ing a beneficial effect of foods with a high isoflavone content on menopausal symptoms may have been confounded by a large placebo response Objective : To investigate the effects of a novel dietary supplement containing soy isoflavones and Actaea racemosa Linnaeus ( formerly called Cimicifuga racemosa L. ) on climacteric symptoms in healthy perimenopausal women . Design : In a multicenter , r and omized , placebo-controlled , double-blind study , 124 women experiencing at least five vasomotor symptoms every 24 hours were r and omized to receive daily either a phytoestrogen-containing supplement ( n = 60 ) or placebo ( n = 64 ) for 12 weeks . The modified Kupperman Index and Greene Climacteric Scale , a visual analogue scale design ed to measure quality of life and the daily number and severity of hot flushes , was used in the screening period and in weeks 6 and 12 . Changes in these scores from baseline were calculated . Results : At weeks 6 and 12 , all scores in both groups had improved compared with baseline , though the overall difference in scores between the groups was not statistically significant . Conclusion : The supplement containing soy isoflavones and A racemosa L. had no statistically significant effect on climacteric symptoms in perimenopausal women experiencing at least five vasomotor symptoms per day OBJECTIVES To evaluate the preliminary efficacy and safety of Pueraria mirifica in the treatment of vasomotor symptoms . DESIGN Open-label study . SETTING Hat Yai Regional Hospital , Thail and . SUBJECTS Pre and postmenopausal women with vasomotor symptoms , such as hot flushes and night sweats . Other unpleasant symptoms , urogenital and psychological symptoms , were also evaluated . MATERIAL AND METHOD Patients were enrolled voluntarily and r and omly received 50 mg or 100 mg of Pueraria mirifica in capsules , once daily for six months . RESULTS Of the 48 enrolled patients , 11 cases were excluded for failing to complete the initial work-up . Thirty-seven cases were evaluated . 20 of 37 ( 54.1 % ) r and omly received a dose of 50 mg/day of Pueraria mirifica ( Group A ) , and 17 of 37 ( 45.9 % ) received 100 mg/day of Pueraria mirifica ( Group B ) . The mean of the modified Greene climacteric scale decreased from 35.6 to 26.6 , 17.2 and 15.1 in group A , while group B , declined from 32.6 to 21.0 , 14.8 and 13.6 at 1- , 3- and 6-month respectively . The mean serum estradiol , fluctuated from the baseline of 76.6 to 55.4 , 56.7 , 72.5 , 69.2 , 114.2 and 74.5 pg/ml at 1- , 2- , 3- , 4- , 5- and 6-month respectively . Whereas the mean serum follicle-stimulating hormone (FSH)/luteinizing hormone ( LH ) was stable in the range of ; 27.1/12.6 , 28.3/12.9 and 22.5/11.4 mIU/ml at baseline , 3- and 6-month respectively . CONCLUSIONS Pueraria mirifica , containing phytoestrogens , relatively alleviated the climacteric symptoms in perimenopausal women . The transient negative profiles occurred in a small number of subjects that included anemia , and liver profiles . While there was a slight decrease in lipoproteins and an increase in hormonal profiles , Pueraria mirifica demonstrates great promise in the treatment of climacteric symptoms among perimenopausal women . However , optimal doses should be clinical ly assessed , to meet appropriate individual responses Objective To analyze the impact of soy protein dietary supplements containing phytoestrogens on menopausal symptoms in healthy postmenopausal women . Methods A double-blind , placebo-controlled trial was conducted in 94 healthy postmenopausal women aged 50–75 years , with 44 r and omized to soy supplements containing 118 mg of isoflavones ( daidzein , genistein , glycitein and their respective glycosides ) , and 50 to an identically presented casein placebo . A vali date d question naire on menopausal symptoms was administered at baseline and at 3 months of treatment . Compliance was assessed by high-performance liquid chromatography assay of urinary phytoestrogens . Statistical analysis was completed using non-parametric statistical methods and multivariate analysis . Results At baseline 80 % of women recruited were experiencing menopausal symptoms , although symptom severity was mild . Those consuming phytoestrogen supplements had 13- and 17-fold increases in urinary excretion of genistein and daidzein , respectively , with no change in the placebo group . Active soy supplements did not significantly alter either individual symptoms or specific symptom category scores when compared to placebo . Within-group comparisons revealed that the active group reported a significant improvement in vaginal dryness ( p = 0.01 ) , libido ( p = 0.009 ) , facial hair ( p = 0.04 ) and dry skin ( p = 0.027 ) . However , similarly , those on placebo reported an improvement in libido ( p = 0.015 ) , facial hair ( p = 0.014 ) and dry skin ( p = 0.011 ) but not vaginal dryness . Conclusions In this group of 94 older postmenopausal women with a high frequency of mild menopausal symptoms , 3 months of soy supplements containing phytoestrogens did not provide symptomatic relief compared with placebo 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 OBJECTIVES To assess the efficacy of a product containing isoflavones and other plant extracts ( BIO ) on whole menopausal symptomatology and plasma lipids profile . METHODS Multicentre , r and omized , double blind , placebo controlled clinical investigation on 125 menopausal women r and omly assigned to two groups treated for 6 months with placebo or one tablet daily of an herbal product containing 72 mg/dose of isoflavones of different plants origin and other plant extracts ( BIO ) . Primary end-point : Kupperman Menopause Index ( KI ) variations ; secondary end-point : activity on plasma lipids profile and clinical global impression ( CGI ) on efficacy and tolerability by investigators and patients . The usual parametric test ( paired Student t test ) was performed to evaluate the significance . In case of non-applicability of parametric tests , the non-parametric Mann-Whitney U test was used . The differences where considered significant at p<0.05 level . RESULTS At the end of treatment in both groups KI showed a significant decrease ( p<0.001 ) . However , in the BIO group the KI reduction was significantly higher ( p=0.0265 ) than in the placebo group after 4 and 6 months of treatment . In the BIO treated patients the LDL cholesterol showed a borderline but not significant reduction compared to placebo ( p=0.0608 ) and triglyceride ( TG ) a significant ( p=0.0151 ) decrease compared to placebo . The investigator 's and patient 's CGI on BIO group where superior as compared to placebo . Clinical tolerability was good in booth groups . CONCLUSION On the basis of positive effects on KI and lipids profile as well as of good clinical tolerability , BIO can be considered one of the possible alternative therapy for conventional HRT AIM Dietary soy supplementation may reduce the incidence of hot flushes in postmenopausal women due to the presence of phytoestrogens in soy foods . The aim of this study was to assess the effects of a 3-month administration of different doses of either oral or transdermal soy isoflavones on climacteric complaints in postmenopausal women . METHODS Sixty postmenopausal women were assigned r and omly to one of the following groups : groups A and B received 50 mg/day or 75 mg/day of oral isoflavones respectively , while groups C and D received 6 mg/day or 12 mg/day of transdermal isoflavones . A control group ( group E ) was composed of 15 patients that did not receive any treatment . Hot flushes , Kupper-man index and vaginal dryness at baseline and then after 5 , 9 and 13 weeks were evaluated . RESULTS The isoflavone treatment led to a progressive significant ( p<0.01 ) reduction of the number of hot flushes in the groups A , B and D with a dose-related effect in group D. At week 13 , the Kupperman index and hot flush score decreased significantly in all the treated groups , while vaginal dryness score was reduced only in group B. CONCLUSION Our findings suggest that both oral and transdermal soy isoflavones are effective to attenuate slight to moderate menopausal neurovegetative symptoms with a dose-related effect It has been well documented that the frequency of vasomotor menopausal symptoms , such as hot flashes and night sweats , of Japanese menopausal women is less than that of Western women . High intake of soy isoflavones in the traditional Japanese diet has been postulated as the possible explanation of the difference . Epidemiological studies have reported that the content of equol , which is a biologically active metabolite of the isoflavone , daidzein , is lower in the women who complain of severe vasomotor symptoms . To investigate the involvement of equol in the manifestation of menopausal symptoms , especially vasomotor symptoms , and the possible therapeutic role of a supplement containing equol ( natural S-equol developed by Otsuka Pharmaceutical ) on the menopausal symptoms of Japanese women , 3 r and omized clinical trials were conducted . The studies indicated that a daily dose of 10 mg of natural S-equol improved menopausal symptoms . In the confirmation study , menopausal women who were equol nonproducers who consumed 10 mg/d of natural S-equol for 12 wk had significantly reduced severity and frequency of hot flashes as well as a significant reduction in the severity of neck or shoulder stiffness . The equol-ingesting group also showed trends of improvement in sweating and irritability and a significant improvement in the somatic category symptoms . Thus , it is concluded that the supplement containing natural S-equol , a novel soybean-derived functional component , has a promising role as an alternative remedy in the management of menopausal symptoms OBJECTIVE To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Centre of Perinatal and Reproductive Medicine , Department of Gynecological , Obstetrical , and Pediatric Sciences , University of Perugia , Italy . PATIENT(S ) Three hundred seventy-six postmenopausal healthy women , all with intact uterus . INTERVENTION(S ) Women were distributed in two different groups using r and omized criteria : group A ( n = 179 ) patients received soy tablets ( 150 mg of isoflavones per day ) for 5 years ; group B ( n = 197 ) patients received identical appearing placebo tablets for 5 years . MAIN OUTCOME MEASURE(S ) Results of endometrial histology from biopsies obtained at baseline , 30 months , and 5 years after the beginning of the treatment . RESULT ( S ) Two hundred ninety-eight women completed the 5-year treatment . No cases of malignancy were detected during biopsy . Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81 % receiving placebo . The occurrence of endometrial hyperplasia was significantly higher in group A ( 3.37 % vs. 0 % ) . CONCLUSION ( S ) Long-term treatment ( up to 5 years ) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia . These findings call into question the long-term safety of phytoestrogens with regard to the endometrium The objective of this study was to evaluate the efficacy of flaxseed meal and flaxseed extract in reducing climacteric symptoms of menopausal women . Ninety menopausal women were r and omly distributed into three study groups : group I received 1 g per day of flaxseed extract containing at least 100 mg of secoisolariciresinol diglucoside ( SDG ) , group II received 90 g per day of flaxseed meal containing at least 270 mg of SDG , and group III received 1 g per day of collagen ( placebo group ) . Subjects were assessed for menopausal symptoms by the Kupperman index at the beginning and at the end of the 6 months of treatment . Subjects were also assessed for endometrial thickness and vaginal cytology . The Kupperman index values at the beginning and end of the treatments were analyzed using the paired t-test . Both the flaxseed extract ( P=.007 ) and the flaxseed meal ( P=.005 ) were effective in reducing the menopausal symptoms when compared with the placebo control ( P=.082 ) . Alternatively , the changes in Kupperman index were also computed and su bmi tted to analysis of variance . In this case , no significant differences were found ( P=.084 ) although the data indicate a decreasing tendency for the Kupperman index by both the flaxseed extract and the flaxseed meal groups . Neither the flaxseed extract nor the flaxseed meal exerted clinical ly important estrogenic effects on the vaginal epithelium or endometrium as revealed by the absence of changes in the blood levels of follicle stimulating hormone and estradiol , as well as in the endometrial thickness , and vaginal epithelial maturation value . No serious adverse events related to the treatments were reported . Although the results of the present study do not allow an unequivocal conclusion about the action of flaxseed on the menopausal symptoms , they suggest that it could be premature to conclude that no such action exists . Clearly the matter still deserves further experimental attention
target: 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: 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 .