***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 . 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 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 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 Objective : This project was design ed to provide an overview of hot flash studies conducted over the past two decades at the Mayo Clinic and in the North Central Cancer Treatment Group . Design : Prospect i ve clinical trials performed by these investigators are illustrated , described , and discussed . Results : Ten r and omized , controlled ( eight  placebo controlled ) , double-blind clinical trials were conducted involving a total of 1,581 women and three placebo-controlled , double-blind clinical trials involving a total of 329 men were conducted . In addition , 14 pilot trials , having involved more than 325 participants to date , were conducted . Conclusions : Data from the pilot trials have given direction for substances that ought to be further explored in more definitive studies . In men , r and omized studies demonstrate that hot flashes are markedly decreased by low doses of megestrol acetate , moderately decreased by gabapentin , but not substantially decreased by clonidine . Results from the r and omized trials in women demonstrate that hot flashes are markedly decreased by relatively low doses of progestational agents ( megestrol acetate and medroxyprogesterone acetate ) , moderately decreased by venlafaxine , mildly to moderately decreased by fluoxetine , mildly decreased by clonidine , but not substantially decreased by vitamin E , a soy phytoestrogen product , or black cohosh . Last , the data investigated in these studies support the hypothesis that , for the treatment of hot flashes in women , the results of therapeutic maneuvers are similar regardless of whether the patient has a history of breast cancer and /or is taking tamoxifen CONTEXT The Heart and Estrogen/progestin Replacement Study ( HERS ) found no overall reduction in risk of coronary heart disease ( CHD ) events among postmenopausal women with CHD . However , in the hormone group , findings did suggest a higher risk of CHD events during the first year , and a decreased risk during years 3 to 5 . OBJECTIVE To determine if the risk reduction observed in the later years of HERS persisted and result ed in an overall reduced risk of CHD events with additional years of follow-up . DESIGN AND SETTING R and omized , blinded , placebo-controlled trial of 4.1 years ' duration ( HERS ) and subsequent unblinded follow-up for 2.7 years ( HERS II ) conducted at outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS ; 2321 women ( 93 % of those surviving ) consented to follow-up in HERS II . INTERVENTION Participants were r and omly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate ( n = 1380 ) , or placebo ( n = 1383 ) during HERS ; open-label hormone therapy was prescribed at personal physicians ' discretion during HERS II . The proportions with at least 80 % adherence to hormones declined from 81 % ( year 1 ) to 45 % ( year 6 ) in the hormone group , and increased from 0 % ( year 1 ) to 8 % ( year 6 ) in the placebo group . MAIN OUTCOME MEASURES The primary outcome was nonfatal myocardial infa rct ion and CHD death . Secondary cardiovascular events were coronary revascularization , hospitalization for unstable angina or congestive heart failure , nonfatal ventricular arrhythmia , sudden death , stroke or transient ischemic attack , and peripheral arterial disease . RESULTS There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS , HERS II , or overall . The unadjusted relative hazard ( RH ) for CHD events in HERS was 0.99 ( 95 % confidence interval [ CI ] , 0.81 - 1.22 ) ; HERS II , 1.00 ( 95 % CI , 0.77 - 1.29 ) ; and overall , 0.99 ( 0.84 - 1.17 ) . The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups ( RH , 0.97 ; 95 % CI , 0.82 - 1.14 ) , and in analyses restricted to women who were adherent to r and omized treatment assignment ( RH , 0.96 ; 95 % CI , 0.77 - 1.19 ) . CONCLUSIONS Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up . After 6.8 years , hormone therapy did not reduce risk of cardiovascular events in women with CHD . Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD 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 OBJECTIVE To report the histological findings of the endometrium of postmenopausal women who were r and omized to receive placebo , estrogen only , or one of three estrogen plus progestin ( E+P ) regimens in the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial . DESIGN A 3-year multicenter , r and omized , double-masked , placebo-controlled trial . PARTICIPANTS A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy . INTERVENTION Participants were r and omized and stratified in equal numbers to one of the following treatments in 28-day cycles : placebo , 0.625 mg/d of conjugated equine estrogens ( CEE ) , 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate ( MPA ) for the first 12 days , 0.625 mg/d of CEE plus 2.5 mg/d of MPA , or 0 
    Output:
    
Isoflavone supplements providing more than 18.8 mg of genistein ( the median for all studies ) were more than twice as potent at reducing hot flash frequency than lower genistein supplements .
Conclusions Soy isoflavone supplements , derived by extraction or chemical synthesis , are significantly more effective than placebo in reducing the frequency and severity of hot flashes .