human
***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: 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 
    Output:
    
agent
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 .
***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: 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 
    Output:
    