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. Effects of soy protein isolate on bone mineral density and physical performance indices in postmenopausal women-a 2-year randomized, double-blind, placebo-controlled trial Association between dietary phyto-oestrogens and bone density in men and postmenopausal women. Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial. Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial Hormone therapy and physical function change among older women in the Women's Health Initiative: a randomized controlled trial The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women. Higher bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans compared with glucoside-rich non-fermented soybeans in Japanese postmenopausal women. One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study Red clover isoflavones enriched with formononetin lower serum LDL cholesterol—a randomized, double-blind, placebo-controlled study Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer Phytoestrogen and multiple vitamin/mineral effects on bone mineral density in early postmenopausal women: a pilot study. The effects of soy isoflavone on bone density in north region of climacteric Chinese women Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women Effects of soya isoflavones and exercise on body composition and clinical risk factors of cardiovascular diseases in overweight postmenopausal women: a 6-month double-blind controlled trial. The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Design and baseline characteristics of a trial on health effects of soy protein with isoflavones in postmenopausal women. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women. Prevalence of menopause symptoms and their association with lifestyle among Finnish middle-aged women. Soymilk or progesterone
  for prevention of bone loss Soy protein and bone mineral density in older men and women: a randomized trial. Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Design and baseline characteristics of the soy phytoestrogens as replacement estrogen (SPARE) study--a clinical trial of the effects of soy isoflavones in menopausal women. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. [Relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density of Chinese postmenopausal women]. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. Soy isoflavones attenuate bone loss in early postmenopausal Chinese women Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial.
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 : Postmenopausal decreases in body composition , physical performance , and bone mass have been shown to be reversed by estrogen , but given the concerns regarding its use , women are looking for alternatives such as soy isoflavones . Most studies on the effects of soy on bone mineral density ( BMD ) in postmenopausal women have been short-term , that is , 3 to 6 months , and failed to provide conclusive evidence . There is no evidence of its effects on physical performance . The aim of the present study was to investigate the effects of soy plus isoflavones on BMD and physical performance in postmenopausal women . Methods : This was a 2-year r and omized controlled trial . A total of 203 healthy postmenopausal women were given either 25 g of soy protein without isoflavones , 25 g of soy protein with 90 mg of isoflavones , or 25 g of milk protein ( casein and whey ) as a control agent for 24 months . Women were followed every 6 months with BMD and physical performance measurements for 2 years . Primary analysis was intent-to-treat analysis . Analysis of variance , & khgr;2 and Fisher 's exact tests , and analysis of covariance were used . Results : There was a significant decrease in the BMD of the lumbar spine and femoral neck in those who completed the study in all groups . Soy isoflavones prevented major bone loss from baseline at the femoral trochanter with no between-group significance . Physical performance measurements decreased in all the groups . Conclusions : Twenty-five grams of soy protein with 90 mg of isoflavones has no added benefit in preventing bone loss or improving physical performance Phyto-oestrogens have been associated with a decreased risk for osteoporosis , but results from intervention and observational studies in Western countries have been inconsistent . In the present study , we investigated the association between habitual phyto-oestrogen intake and broadb and ultrasound attenuation ( BUA ) of the calcanaeum as a marker of bone density . We collected 7 d records of diet , medical history and demographic and anthropometric data from participants ( aged 45 - 75 years ) in the European Prospect i ve Investigation into Cancer-Norfolk study .  Phyto-oestrogen ( biochanin A , daidzein , formononetin ; genistein , glycitein ; matairesinol ; secoisolariciresinol ; enterolactone ; equol ) intake was determined using a newly developed food composition data base . Bone density was assessed using BUA of the calcanaeum . Associations between bone density and phyto-oestrogen intake were investigated in 2580 postmenopausal women who were not on hormone replacement therapy and 4973 men .  Median intake of total phyto-oestrogens  was 876 ( interquartile range 412 ) μg/d in postmenopausal women and 1212 ( interquartile range 604 ) μg/d in men . The non-soya isoflavones formononetin and biochanin A were marginally significant or significantly associated with BUA in postmenopausal women ( β = 1·2 ; P < 0·1 ) and men ( β = 1·2 ; P < 0·05 ) , respectively ; enterolignans and equol were positively associated with bone density in postmenopausal women , but this association became non-significant when dietary Ca was added to the model . In the lowest quintile of Ca intake , soya isoflavones were positively associated with bone density in postmenopausal women ( β = 1·4 ; P < 0·1 ) . The present results therefore suggest that non-soya isoflavones are associated with bone density independent of Ca , whereas the association with soya or soya isoflavones is affected by dietary Ca OBJECTIVES To compare the effect of a soy rich diet and hormone replacement therapy ( HRT ) on the main biomarkers of bone turnover and bone mineral density ( BMD ) at postmenopausal age . METHODS 187 healthy asymptomatic postmenopausal women , aged 39 - 60 , were recruited and r and omized into a soy rich diet group , a HRT group , and a control group .  Bone biomarkers and BMD were evaluated at baseline and after 6 months at the end of the study . RESULTS Diet is not as effective as HRT in reducing the postmenopausal turnover ; however diet stimulates bone osteoblastic activity , as evidence d by significant increase in osteocalcin concentrations . BMD decreases significantly only in the control group , but not in the intervention groups . CONCLUSIONS Our data suggest that soy products could be effective in reducing the risk of osteoporosis in asymptomatic postmenopausal women , but our findings should be confirmed before recommending the diet as a valid alternative to HRT Objective : Equol is more biologically active than its precursor daidzein , which is the principal isoflavone found in soybean . There are interindividual differences in the ability to produce equol ; these may lead to differences in the effects of isoflavone intervention on human health . This study aim ed to investigate whether the effects of soy isoflavones on bone and fat mass are related to an individual 's equol status . Design : We performed a 1-year double-blind , r and omized trial to compare the effects of isoflavone ( 75 mg of isoflavone conjugates/day ) with those of placebo on bone mineral density , fat mass , and serum isoflavone concentrations in early postmenopausal Japanese women who were classified based on their equol-producer phenotype . Results : After 1 year , the isoflavone intervention significantly increased the serum equol concentration in the equol producers but not in the nonproducers . In the isoflavone group , the annualized changes in the bone mineral density of the total hip and intertrochanteric regions were −0.46 % and −0.04 % , respectively , in the equol producers and −2.28 % and −2.61 % , respectively , in the nonproducers ; these values were significantly different ( P < 0.05 for both the regions ) . Significant differences were observed between the equol producers and nonproducers in the isoflavone group with regard to the annualized changes in the fat mass . No significant difference in the annualized changes in bone mineral density and fat mass was observed between the equol producers and nonproducers in the placebo group . Conclusions : Our data suggest that the preventive effects of isoflavones on bone loss and fat accumulation in early postmenopausal women depend on an individual 's equol-producing capacity Objective : Although estrogen may be linked to biological pathways that maintain higher physical function , the evidence is derived mostly from observational epidemiology and therefore has numerous limitations . We examined whether hormone therapy affected physical function in women 65 to 79 years of age at enrollment . Methods : This study involves an analysis of the Women 's Health Initiative r and omized controlled trials of hormone therapy in which 922 nondisabled women who had previous hysterectomies were r and omized to receive estrogen therapy or a placebo and 1,458 nondisabled women with intact uteri were r and omized to receive estrogen + progestin therapy or a placebo . Changes in physical function were analyzed for treatment effect , and subgroup differences were evaluated . All women completed performance-based measures of physical function ( grip strength , chair st and s , and timed walk ) at baseline . These measures were repeated after 1 , 3 , and 6 years . Results : Overall , participants ' grip strength declined by 12.0 % , chair st and s declined by 3.5 % , and walk pace slowed by 11.4 % in the 6 years of follow-up ( all P values < 0.0001 ) . Hormone therapy , as compared with placebo , was not associated with an increased or decreased risk of decline in physical function in either the intention-to-treat analyses or in analyses restricted to participants who were compliant in taking study pills . Conclusions : Hormone therapy provided no overall protection against functional decline in nondisabled postmenopausal women 65 years or older in 6 years of follow-up . This study did not address the influence of hormone therapy for women of younger ages BACKGROUND Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy ( HRT ) . HRT has a beneficial effect on bone , but few trials in humans have investigated the effects of isoflavones on bone . OBJECTIVE The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A , 16 mg formononetin , 1 mg genistein , and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied . DESIGN Women aged 49 - 65 y ( n = 205 ) were enrolled in a double-blind , r and omized , placebo-controlled trial ; 177 completed the trial .  Bone density , body composition , bone turnover markers , and diet were measured at baseline and after 12 mo . RESULTS Loss of lumbar spine bone mineral content and bone mineral density was significantly ( P = 0.04 and P = 0.03 , respectively ) lower in the women taking the isoflavone supplement  than in those taking the placebo . There were no significant treatment effects on hip bone mineral content or bone mineral density , markers of bone resorption , or body composition , but bone formation markers were significantly increased ( P = 0.04 and P = 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I , respectively ) in the intervention group compared with placebo in postmenopausal women . Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant . CONCLUSION These data suggest that , through attenuation of bone loss , isoflavones have a potentially protective effect on the lumbar spine in women BACKGROUND No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover  in perimenopausal women . OBJECTIVE Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones ( 80.4 mg/d ) in attenuating bone loss during the menopausal transition . DESIGN Perimenopausal subjects were r and omly assigned , double blind , to treatment : isoflavone-rich soy ( SPI+ ; n = 24 ) , isoflavone-poor soy ( SPI- ; n = 24 ) , or whey ( control ; n = 21 ) protein . At baseline and posttreatment , lumbar spine bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured by using dual-energy X-ray absorptiometry . At baseline , midtreatment , and posttreatment , urinary N:-telopeptides and serum bone-specific alkaline phosphatase ( BAP ) were measured . RESULTS The percentage change in lumbar spine BMD and BMC , respectively , did not differ from zero in the SPI+ or SPI- groups , but loss occurred in the control group ( -1.28 % , P : = 0.0041 ; -1.73 % , P : = 0.0037 ) . By regression analysis , SPI+ treatment had a positive effect on change in BMD ( 5.6 % ; P : = 0.023 ) and BMC ( 10.1 % ; P : = 0.0032 ) . Baseline BMD and BMC ( P : < or = 0.0001 ) negatively affected the percentage change in their respective models ; baseline body weight ( P : = 0.0036 ) and bone-free lean weight ( P : = 0.016 ) contributed positively to percentage change in BMD and BMC , respectively . Serum BAP posttreatment was negatively related to percentage change in BMD ( P : = 0.0016 ) and BMC ( P : = 0.019 ) . Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones , not soy protein , exerted the effect . CONCLUSION Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P < 0.05 ) . CONCLUSIONS Because soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447 Our previous study on bone health among premenopausal women showed that bone mass consolidation is attained by the early 30s , and small loss of spinal bone mineral density ( SBMD ) occurs soon after peak bone mass attainment . Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health . However , data are lacking , particularly in Asian women . This study aims to investigate the effect of soy isoflavones intake on the maintenance of peak bone mass in a cohort of 132 women aged 30 - 40 years who were followed up for 3 years . Baseline measurements of SBMD ( L2-L4 ) were obtained using dual-energy X-ray densitometry , and dietary intake of soy foods and other key nutrients , including dietary calcium , were obtained through a quantitative food frequency method . Information on body measurements ; physical activity ( PA ) , weight-bearing activity in particular ; age of menarche ; and number of pregnancies were obtained at baseline . Repeated measurements of SBMD were obtained yearly for a further 3 years with an average follow-up time of 38 months . Analyses were performed on 116 subjects with at least three SBMD measurements ( at baseline , 3-year follow-up , and at least one measurement during follow-up ) . The individual SBMD regression slope was computed for each of the subjects . Soy isoflavones consumption was categorized as quartiles of intake . We observed a significant difference in the SBMD individual regression slopes between women belonging to the fourth and first soy isoflavones intake quartiles . The positive effect of soy isoflavones on SBMD remained after adjusting for age and body size ( height , weight , and bone area ) . Multiple linear regression analysis including the other known covariates ( lean body mass , PA , energy adjusted calcium , and follow-up time ) showed that soy isoflavones , together with these variables , accounted for 24 % of the variances of the SBMD individual regression slope . This longitudinal study shows that soy intake had a significant effect on the maintenance of SBMD in women aged 30 - 40 years . The effects of phytoestrogens on bone health should be explored further in a population with habitual dietary soy  but low calcium intake BACKGROUND There have been conflicting study results concerning how the food matrix affects the bioavailability of isoflavone aglycone and glucoside . In this study the bioavailability of isoflavones  after a single ingestion of aglycone-rich fermented soybeans ( Fsoy ) and glucoside-rich non-fermented soybeans ( Soy ) was compared . Eleven healthy postmenopausal Japanese women were recruited for a r and omised , double-blind , crossover trial and consumed Fsoy or Soy powder dissolved in hot water . Blood sample s were collected 0 , 1 , 2 , 3 , 4 , 6 , 8 , 12 and 24 h and urine sample s from 0 to 48 h after ingestion of the powders . The Fsoy and Soy powders ingested had the same total isoflavone content ( 95 µmol ) , but the former was rich in aglycone ( 90.6 µmol ) while the latter was rich in glucoside ( 81.9 µmol ) . RESULTS Serum concentrations of total isoflavones after 1 - 4 h were significantly higher in the Fsoy group than in the Soy group . The Fsoy group showed significantly higher maximum concentration ( Cmax : 2.79 ± 0.13 vs 1.74 ± 0.13 µmol L(-1 ) ) and area under the curve ( AUC(0 - 24 h ) : 23.78 ± 2.41 vs 19.95 ± 2.03 µmol day L(-1 ) ) and lower maximum concentration time ( Tmax : 1.00 ± 0.00 vs 5.00 ± 0.67 h ) compared with the Soy group . The cumulative urinary excretion of total isoflavones after 2 h was significantly higher in the Fsoy group than in the Soy group . Individual isoflavones ( daidzein , genistein and glycitein ) showed similar trends to total isoflavones . Equol ( a metabolite from daidzein ) did not differ between the two groups . CONCLUSION The results of this study demonstrated that the isoflavones of aglycone-rich Fsoy were absorbed faster and in greater amounts than those of glucoside-rich Soy in postmenopausal Japanese women Background Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women , most of these studies are of short duration ( i.e. six months ) . The objective of this study was to examine if one year consumption of soy-containing foods ( providing 25 g protein and 60 mg isoflavones ) exerts beneficial effects on bone in postmenopausal women . Methods Eighty-seven eligible postmenopausal women were r and omly assigned to consume soy or control foods daily for one year . Bone mineral density ( BMD ) and bone mineral content ( BMC ) of the whole body , lumbar ( L1-L4 ) , and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year . Blood and urine markers of bone metabolism were also assessed . Results and Discussion Sixty-two subjects completed the one-year long study . Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups . However , there were no significant changes in total hip BMD and BMC irrespective of treatment . Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase ( BSAP ) activity , insulin-like growth factor-I ( IGF-I ) , and osteocalcin ( BSAP : 27.8 and 25.8 % , IGF-I : 12.8 and 26.3 % , osteocalcin : 95.2 and 103.4 % for control and soy groups , respectively ) . Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion , a marker of bone resorption . Conclusion Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation , this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women Purpose Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis . Soybean isoflavones , especially genistein , are being studied for this purpose . This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density ( BMD ) in early postmenopausal women . Methods In this 6-month double-blind pilot study , 70 subjects were r and omized to receive daily either calcium only or the geniVida ™ bone blend ( GBB ) , which consisted of genistein ( 30 mg/days ) , vitamin D3 ( 800 IU/days ) , vitamin K1 ( 150 μg/days ) and polyunsaturated fatty acids ( 1 g polyunsaturated fatty acids as ethyl ester : eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1 ) . Markers of bone resorption and formation and BMD at the femoral neck , lumbar spine , Ward ’s triangle , trochanter and intertrochanter , total hip and whole body were assessed . Results Subjects supplemented with the GBB ( n = 30 ) maintained femoral neck BMD , whereas in the placebo group ( n = 28 ) , BMD significantly decreased ( p = 0.007 ) . There was also a significant difference ( p < 0.05 ) in BMD between the groups at Ward ’s triangle in favor of the GBB group . Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group . The GBB was well tolerated , and there were no significant differences in adverse events between groups . Conclusions The GBB may help to prevent osteoporosis and reduce fracture risk , at least at the hip , in postmenopausal women . Larger and longer-term clinical trials are warranted Background : Although postmenopausal combined hormone replacement therapy reduces the risk of hip fracture , long-term use may be associated with an increased risk of breast cancer , and in women more than 10 years after menopause it is associated with an increased risk of cardiovascular disease . Isoflavones , because of preferential binding to estrogen receptor beta , may retain the beneficial effects on bone but lessen the adverse effects on the breast . Objective : The objective of this study was to study the effects of an isoflavone obtained from red clover ( Rimostil ) on bone mineral density , and on low-density lipoprotein ( LDL ) cholesterol . Design : In a double-blind , r and omized , placebo-controlled trial , 50 mg of Rimostil was given to women who were menopausal for at least 1 year .  Bone mineral density of the spine , femoral neck and forearm and serum LDL cholesterol were measured at baseline and at 6-month intervals . The duration of follow-up was 2 years . Results : There was no beneficial effect of Rimostil  on bone density at any site . There was a 12 % fall in serum LDL cholesterol in the Rimostil-treated arm , which was significantly greater than the 2 % drop seen in the control arm ( P=0.005 ) Objective To assess the safety and tolerability of a st and ardized 40 mg red clover isoflavone dietary supplement ( Promensil ® , Novogen ) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women . Study design Healthy women aged 35–70 years ( n = 401 ) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a r and omized , double-blind , placebo-controlled pilot trial . Participants were assessed clinical ly and blood sample s taken for biochemical analysis every six months . In addition , study participants underwent mammography , bone density and transvaginal ultrasound ( postmenopausal women only ) once per year . Results No significant differences in breast density , endometrial thickness , serum cholesterol , follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo . In postmenopausal women , some significant differences in bone marker levels were seen between active and placebo groups , at six months and at 12 months . The adverse event profile was similar across all red clover isoflavone and placebo groups . Conclusion This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women . Supplements containing red clover isoflavones did not adversely affect breast density , skeletal strength or cardiovascular status . In postmenopausal women , endometrial status was not adversely affected . The adverse event profile was similar between red clover isoflavones , and placebo and endocrine status did not differ The purpose of the study was to assess the effect of a combination regimen of herbs , vitamins , and minerals on bone mineral density ( BMD ) in early postmenopausal women via a 2-year , single-blind , uncontrolled , prospect i ve trial . BMD was measured by dual energy x-ray absorptiometry ( DEXA ) at baseline and at 6 , 12 , and 24 months . Results of lumbar spine , hip , and forearm densities did not differ significantly from historical controls derived from other recent trials using a similar patient population . Bone mineral losses are reported on an annualized basis over the 2 years for the 12 women who completed the trial : spine ( -1.42 % per year ) , hip ( -0.43 % per year ) , forearm ( -1.42 % per year ) . Six women were withdrawn from the trial by the investigators because of excessive losses of bone mineral , and 1 of these women was diagnosed with hyperparathyroidism .  There were no metabolic diseases to explain the losses in the remaining 5 withdrawn subjects . Four of 21 subjects experienced adverse side effects , necessitating dropping out by 3 of these women . In conclusion , the combined treatment regimen of a menopause symptom-oriented herbal blend plus a high potency vitamin/mineral was unsuccessful in protecting women against the predictable acceleration of bone mineral losses associated with early postmenopause Only a few investigations were based on limb bone density . This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders , limb bone density and the role of pathway . The research protocol involved the r and om subdivision of the enrolled sample into two groups of 40 women , who were to receive treatment for 6 months with isoflavone ( 90 mg/day ) and with placebo .  All of the patients were asked to fill in a question naire concerning their complaints . BMD of the radius and tibia were measured using quantitative ultrasound . Bone metabolism indexes calcium , phosphorus and alkaline phosphatase ( ALP ) were examined regularly . Serum cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) examined by ELISA . The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders . Compared with placebo , the tibia bone density in isoflavone group increased obviously against the base value before trail . Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo . For climacteric women  , soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density , which maybe had the relationship with the levels of IL-6 , TNF-α and ALP in serum Objective . To investigate the effect by which daily consumption of a novel red clover ( RC ) extract influences bone health , inflammatory status , and cardiovascular health in healthy menopausal women . Design . A 12-week r and omized , double-blinded , placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones ( 33.8 mg as aglycones ) or placebo . Methods . Bone parameters were changes in bone mineral density ( BMD ) , bone mineral content ( BMC ) , and T-score at the lumbar spine and femoral neck . Bone turnover ( CTx ) and inflammatory markers were measured in plasma and finally blood pressure ( BP ) was evaluated . Results . RC extract had positive effect on bone health , and only the women receiving the placebo experienced a decline in BMD ( p < 0.01 ) at the lumbar spine . T-score at the lumbar spine only decreased in the placebo group ( p < 0.01 ) . CTx decreased in the RC group with −9.94 (±4.93)% , although not significant . Conclusion . Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health  in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels . No changes in BP or inflammation markers were found and no side effects were observed Results from a pilot project indicate that isoflavones and exercise could have an additive effect on body composition and clinical risk factors of CVD in postmenopausal women . The objective of the present study was to assess the combined effect of exercise and isoflavones in overweight-to-obese postmenopausal women . In this double-blind r and omised controlled trial , 100 overweight-to-obese ( BMI 29·9 ( sd 3·2 ) kg/m2 ) postmenopausal women were assigned to four groups : ( 1 ) placebo ( PLA ) ; ( 2 ) isoflavones ( ISO ) ; ( 3 ) exercise and placebo ( Ex+PLA ) ; ( 4 ) exercise and isoflavones ( Ex+ISO ) . The supplementation contained 70 mg/d of isoflavones . Exercise consisted of three weekly sessions of resistance training and aerobics . Outcome measures included fat mass ( FM ) , lean body mass ( LBM ) , bone mineral density , lipid profile , fasting glucose , fasting insulin and insulin resistance ( homeostasis assessment model ) . The main effects of exercise were observed for total FM ( P = 0·02 ) , FM% ( P < 0·01 ) , trunk FM% ( P = 0·05 ) , arm FM% ( P < 0·01 ) , leg FM% ( P = 0·02 ) , arm LBM ( P < 0·01 ) , leg LBM ( P = 0·02 ) and C-reactive protein ( P < 0·01 ) . A main effect was detected for isoflavones in improving leg FM% ( P = 0·05 ) . No interactions were observed between isoflavones and exercise . In conclusion , it was observed that 6 months of exercise brought favourable changes in total FM , FM% and LBM in overweight postmenopausal women . No synergistic effects were observed between exercise and isoflavones . However , isoflavones could have a beneficial effect on leg FM% Summary The treatment of 300-mg/day isoflavones ( aglycone equivalents ) ( 172.5 mg genistein + 127.5 mg daidzein ) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density ( BMD ) from declining as compared with the placebo group in a r and omized , double-blind , two-arm design ed study enrolling 431 postmenopausal women 45–65 years old . Introduction This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women . Methods Four hundred and thirty-one women , aged 45–65 years , orally consumed 300-mg/day isoflavones ( aglycone equivalents ) or a placebo for 2 years in a parallel group , r and omized , double-blind , two-arm study . Each participant also ingested 600 mg of calcium and 125 IU of vitamin D3 per day . The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter . Serum bone-specific alkaline phosphatase , urinary N-telopeptide of type 1 collagen/creatinine , and other safety assessment s were examined regularly . Results Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment . Serum concentrations of isoflavone metabolites , genistein and daidzein , of the intervention group were remarkably elevated following intake of isoflavones ( p < 0.001 ) . However , differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant ( lumbar spine , p = 0.42 ; total femur , p = 0.39 ) between the isoflavone and placebo groups , according to the generalized estimating equation ( GEE ) method . A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD ( p < 0.001 ) . Differences in bone marker levels were not significant between the two treatment groups . Conclusion Treatment with 300-mg/day isoflavones ( aglycone equivalents ) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group BACKGROUND Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss  in midlife women . OBJECTIVE We examined the efficacy of isoflavones ( extracted from soy protein ) on bone mineral density ( BMD ) in nonosteoporotic postmenopausal women . We hypothesized that isoflavone tablets would spare BMD , with biological ( age , body weight , serum 25-hydroxyvitamin D ) and lifestyle ( physical activity , dietary intake ) factors modulating BMD loss . DESIGN Our double-blind , r and omized controlled trial ( 36 mo ) included healthy postmenopausal women ( aged 45.8 - 65.0 y ) with intent-to-treat ( n = 224 ) and compliant ( n = 208 ) analyses . Treatment groups consisted of a placebo control group and 2 soy isoflavone groups ( 80 compared with 120 mg/d ) ; women received 500 mg calcium and 600 IU vitamin D(3 ) . Outcomes included lumbar spine , total proximal femur , femoral neck , and whole-body BMD . RESULTS Analysis of variance for intent-to-treat and compliant ( > or = 80 % ) models , respectively , showed no treatment effect for spine ( P = 0.46 , P = 0.21 ) , femur ( P = 0.86 , P = 0.46 ) , neck ( P = 0.17 , P = 0.14 ) , or whole-body ( P = 0.86 , P = 0.78 ) BMD . From baseline to 36 mo , BMD declined regardless of treatment . In intent-to-treat and compliant models , respectively , BMD decreases were as follows : spine ( -2.08 % , -1.99 % ) , femur ( -1.43 % , -1.38 % ) , neck ( -2.56 % , -2.51 % ) , and whole body ( -1.66 % , -1.62 % ) . Regression analysis ( compliant model ) indicated that age , whole-body fat mass , and bone resorption were common predictors of BMD change . After adjustment for these factors , 120 mg ( compared with placebo ) was protective ( P = 0.024 ) for neck BMD . We observed no treatment effect on adverse events , endometrial thickness , or bone markers . CONCLUSION Our results do not show a bone-sparing effect of extracted soy isoflavones , except for a modest effect at the femoral neck . This trial was registered at clinical trials.gov as NCT00043745 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 Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss , but few data are available in humans , especially in the Asian population s. This double-blind , placebo-controlled , r and omized trial examines the effects of soy isoflavones on  bone loss in postmenopausal Chinese women , aged 48 - 62 yr . Two hundred and three eligible subjects were r and omly assigned to three treatment groups with daily doses of placebo ( 1 g starch ; n = 67 ) , mid-dose ( 0.5 g starch , 0.5 g soy extracts , and approximately 40 mg isoflavones ; n = 68 ) , and high dose ( 1.0 g soy extracts and approximately 80 mg isoflavones ; n = 68 ) . All were given 12.5 mmol ( 500 mg ) calcium and 125 IU vitamin D(3 ) . Bone mineral density ( BMD ) and bone mineral content ( BMC ) of the whole body , spine , and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment . Both univariate and multivariate analyses showed that women in the high dose group had mild , but statistically significantly , higher favorable change rate in BMC at the total hip and trochanter ( P < 0.05 ) compared with the placebo and mid-dose groups , even after further adjustments for the potential confounding factors . Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC ( median or less ) . In conclusion , soy isoflavones have a mild , but significant , independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass Soy isoflavones exert inconsistent bone density-preserving effects , but the bone strength-preserving effects in humans are unknown . Our double-blind r and omized controlled trial examined 2 soy isoflavone doses ( 80 or 120mg/d ) vs placebo tablets on volumetric bone mineral density ( vBMD ) and strength ( by means of peripheral quantitative computed tomography ) in healthy postmenopausal women ( 46 - 63yr ) . We measured 3-yr changes in cortical BMD ( CtBMD ) , cortical thickness ( CtThk ) , periosteal circumference ( PC ) , endosteal circumference ( EC ) , and strength-strain index ( SSI ) at 1/3 midshaft femur ( N=171 ) , and trabecular BMD ( TbBMD ) , PC , and SSI at 4 % distal tibia ( N=162 ) . We found no treatment effect on femur CtThk , PC , or EC , or tibia TbBMD or PC . The strongest predictors ( negative ) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption ; whole-body fat mass was protective of SSI . As time since last menstrual period ( TLMP ) increased ( p=0.012 ) , 120-mg/d dose was protective of CtBMD . The strongest predictors of femur SSI were timepoint , bone resorption , and TLMP ( protective ) . Isoflavone tablets were negative predictors of SSI , but 80-mg/d dose became protective as bone turnover increased ( p=0.011 ) . Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased BACKGROUND AND AIM OF THE STUDY The aim of this study is to report the prevalence of menopausal symptoms by severity among the Finnish female population and the association of their symptoms with lifestyle ( smoking , use of alcohol , physical activity ) and body mass index ( BMI ) . MATERIAL AND METHODS Health 2000 is a nationally representative population -based study of Finnish adults . Data were collected by home interview , three self-administered question naires and a clinical examination by a physician . This study included women aged 45 - 64 years ( n=1427 ) . All symptoms included menopause-specific symptoms . Both univariate analysis and a factor analysis based on symptom factors were performed by menopausal group . Multiple regression analysis included each symptom factor as a dependent variable and confounding and lifestyle factors ( age , education , smoking , alcohol use , physical activity , BMI , use of hormonal replacement therapy ( HRT ) and chronic disease status ) . RESULTS Over one-third ( 38 % ) of the premenopausal , half of the perimenopausal , and 54 % of both postmenopausal and hysterectomized women reported bothersome symptoms . The difference between pre- and perimenopausal women was largest and statistically most significant in the case of back pain and hot flushes . Physically active women reported fewer somatic symptoms than did women with a sedentary lifestyle . Smoking was not related to vasomotor symptoms . CONCLUSION Bothersome symptoms are common in midlife , regardless of menopausal status . Inverse association between physical activity and menopausal symptoms needs to be confirmed in r and omized trials Summary Background Given concerns over the use of hormone replacement therapy ( HRT ) , women are seeking natural alternatives to cope with the symptoms and effects of menopause . The bone sparing effects of soy protein and its isoflavones is well established in animal studies , while 5 previous human studies on soy and bone have yielded variable outcomes due in part to their short duration of study . Progesterone has been suggested as a bone – trophic hormone , but the effect of long – term , low dose transdermal progesterone is unknown . Aim The aim of the study was to compare for the first time the long – term effects of soymilk , with or without isoflavones with natural transdermal progesterone , or the combination , on bone mineral density in the lumbar spine and hip . Methods Postmenopausal , Caucasian women with established osteoporosis or at least 3 risk – factors for osteoporosis , were r and omly assigned , double – blind to one of four treatment – groups : soymilk containing isoflavones  ( soy+ , n = 23 ) ,  transdermal progesterone ( TPD+ , n = 22 ) , or the combination of soy+ and TDP+,(n = 22 )  or placebo ( isoflavone – poor soymilk , soy÷ and progesterone – free – cream TDP÷ , n = 22 ) . All subjects received comparable intakes of calcium , minerals and vitamins . Bone mineral content ( BMC ) and density ( BMD ) were measured in lumbar spine and hip by using dual – energy X-ray absorptiometry ( DEXA ) at baseline and after 2 years . Findings The percentage change in lumbar spine BMD and BMC respectively , did not differ from zero in the soy+ group ( + 1.1 % , + 2.0 % ) and TDP+ group ( ÷1.1 % , + 0.4 % ) but significant bone loss occurred in the control group ( ÷4.2%,÷4.3 % ) and the combined treatment group ( ÷2.8 % , ÷2.4 % ) . No significant changes occurred for femoral neck BMD or BMC .InterpretationDaily intake of two glasses of soymilk containing 76 mg isoflavones  prevents lumbar spine bone loss in postmenopausal women . Transdermal progesterone had bone – sparing effects but when combined with soy milk a negative interaction between the two treatments occurs result ing in bone – loss to a greater extent than either treatment alone OBJECTIVE Test the hypothesis that soy isoflavone supplementation preserves bone mineral density ( BMD ) in men and women . METHODS We conducted a controlled , parallel-arm , double-blinded trial with 145 participants , 50 - 80 years , with r and om assignment to soy beverage daily for 12 months . Active treatment ( + ISO ) received soy protein containing 83 mg isoflavones ( 45.6 mg genistein , 31.7 mg daidzein ) , aglycone units ; the comparison group ( -ISO ) received soy protein containing 3 mg isoflavones . We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior-anterior spine ( L1-L4 ) at baseline in 22 women and 123 men , and at 12 months in 13 women and 98 men . We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip . RESULTS Among all participants , mean percent change in spine BMD ( + /-S.E. ) was 0.16+/-0.44 in -ISO ( P=0.10 ) at 12 months . Treatment effects on spine BMD were significantly greater in women than men ( P=0.01 ) . At 12 months , in women , mean percent change was 0.58+/-0.70 in + ISO and -1.84+/-0.86 in -ISO ( P=0.05 ) ; among men it was 1.32+/-0.53 in + ISO and 0.31+/-0.48 in -ISO ( P=0.16 ) . By comparison , percent change in hip BMD was similar in the treatment groups , and was not different between men and women . Mean percent change in hip BMD from baseline to 12 months was 0.54+/-0.38 in + ISO and -0.13+/-0.36 in -ISO ( P=0.20 ) among all participants . CONCLUSIONS Soy protein containing isoflavones showed a modest benefit in preserving spine , but not hip BMD in older women UNLABELLED The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward 's triangle regions . INTRODUCTION The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals . In this study , we determined the effects of isoflavone intake , walking exercise , and their interaction on bone , fat mass , and lipid metabolism over 1 year in postmenopausal Japanese women . MATERIAL S AND METHODS A total of 136 postmenopausal women at < 5 years after the onset of menopause were r and omly assigned to four groups : ( 1 ) placebo , ( 2 ) walking ( 45 minutes/day , 3 days/week ) with placebo , ( 3 ) isoflavone intake ( 75 mg of isoflavone conjugates/day ) , and ( 4 ) combination of isoflavone plus walking .  BMD , fat mass , serum lipid , and serum and urinary isoflavone concentrations were assessed . RESULTS A significant main effect of isoflavone  on the reduction in trunk fat mass was obtained at 12 months . Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3 , 6 , and 12 months and that in the legs and arms at 6 and 12 months . Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention . After 12 months , a significant main effect of isoflavone on BMD was observed only at Ward 's triangle . Walking prevented bone loss at the total hip and the Ward 's triangle to significant degrees . The effect of the combined intervention on BMD at total hip and Ward 's triangle regions was greater than that of either alone . No significant interaction was observed between isoflavone and walking in any measurements recorded during the study . CONCLUSIONS Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward 's triangle regions than either alone . Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners . Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women The natural isoflavone phytoestrogen genistein has been shown to stimulate osteoblastic bone formation , inhibit osteoclastic bone resorption , and prevent bone loss in ovariectomized rats . However , no controlled clinical trial has been performed so far to evaluate the effects of the phytoestrogen on bone loss in postmenopausal women . We performed a r and omized double-blind placebo-controlled study to evaluate and compare with hormone-replacement therapy ( HRT ) the effect of the phytoestrogen genistein on bone metabolism and bone mineral density ( BMD ) in postmenopausal women . Participants were 90 healthy ambulatory women who were 47 - 57 years of age , with a BMD at the femoral neck of < 0.795 g/cm2 . After a 4-week stabilization on a st and ard fat-reduced diet , participants of the study were r and omly assigned to receive continuous HRT for 1 year ( n = 30 ; 1 mg of 17beta-estradiol [ E2 ] combined with 0.5 mg of norethisterone acetate ) , the phytoestrogen genistein ( n = 30 ; 54 mg/day ) , or placebo ( n = 30 ) . Urinary excretion of pyridinoline ( PYR ) and deoxypyridinoline ( DPYR ) was not significantly modified by placebo administration either at 6 months or at 12 months . Genistein treatment significantly reduced the excretion of pyridinium cross-links at 6 months ( PYR = -54 + /- 10 % ; DPYR = -55 + /- 13 % ; p < 0.001 ) and 12 months ( PYR = -42 + /- 12 % ; DPYR = -44 + /- 16 % ; p < 0.001 ) . A similar and not statistically different decrease in excretion of pyridinium cross-links was also observed in the postmenopausal women r and omized to receive HRT . Placebo administration did not change the serum levels of the bone-specific ALP ( B-ALP ) and osteocalcin ( bone Gla protein [ BGP ] ) . In contrast , administration of genistein markedly increased serum B-ALP and BGP either at 6 months ( B-ALP = 23 + /- 4 % ; BGP = 29 + /- 11 % ; p < 0.005 ) or at 12 months ( B-ALP = 25 + /- 7 % ; BGP = 37 + /- 16 % ; p < 0.05 ) . Postmenopausal women treated with HRT had , in contrast , decreased serum B-ALP and BGP levels either at 6 months ( B-ALP = -17 + /- 6 % ; BGP = -20 + /- 9 % ; p < 0.001 ) or 12 months ( B-ALP = -20 + /- 5 % ; BGP = -22 + /- 10 % ; p < 0.001 ) . Furthermore , at the end of the experimental period , genistein and HRT significantly increased BMD in the femur ( femoral neck : genistein = 3.6 + /- 3 % , HRT = 2.4 + /- 2 % , placebo = -0.65 + /- 0.1 % , and p < 0.001 ) and lumbar spine ( genistein = 3 + /- 2 % , HRT = 3.8 + /- 2.7 % , placebo = -1.6 + /- 0.3 % , and p < 0.001 ) . This study confirms the genistein-positive effects on bone loss already observed in the experimental models of osteoporosis and indicates that the phytoestrogen reduces bone resorption and increases bone formation in postmenopausal women OBJECTIVE To investigate the effect of soy isoflavone supplementation on bone mineral density ( BMD ) and markers of bone turnover  in postmenopausal women . METHODS In this r and omized , placebo-controlled clinical trial , we used a crossover design to test the effect of soy isoflavone ( 110 mg/day ) ( 1.3:1.0:0.22 ratio of genistein/daidzein/ glycitein ) on bone formation , bone resorption , bone mineral content ( BMC ) , and BMD for 6 months . RESULTS Postmenopausal women ( n = 19 ) , mean age 70.6 + /- 6.3 years and mean time since menopause 19.1 + /- 5.5 years , were given isoflavone supplements for 6 months . There was a 37 % decrease in urinary concentrations of type 1 collagen alpha1-chain helical peptide ( HP ) , a marker of bone resorption , during the isoflavone supplementation compared with baseline ( p < 0.05 ) and a significant difference in mean ( SE ) HP excretion levels when isoflavone was compared with placebo ( 43.4 + /- 5.2 vs. 56.3 + /- 7.2 microg/mmol creatinine [ cr ] , p < 0.05 ) . With isoflavone supplementation , mean spine BMD at L2 and L3 was significantly greater when treatment was compared with control , with a difference between means of 0.03 + /- 0.04 g and 0.03 + /- 0.04 g ( p < 0.05 ) , respectively . There were nonsignificant increases from baseline for total spine BMC ( 3.5 % ) , total spine BMD ( 1 % ) , total hip BMC ( 3.6 % ) , and total hip BMD ( 1.3 % ) with the isoflavone treatment . CONCLUSIONS Soy isoflavone , in isolated form , was effective in this study to significantly decrease bone resorption  in postmenopausal women . Further investigation needs to be done to evaluate the long-term effects of soy isoflavone on bone mass and fracture risk Objective : Many studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss , but no data reported whether such an effect could be influenced by other important factors affecting bone loss . This study examines whether the associations between isoflavone supplementation and rates of change in bone mineral content ( BMC ) could be modified by years since menopause ( YSM ) , body weight ( BW ) , and dietary calcium intake in postmenopausal Chinese women aged 48 to 62 years . Design : A group of 203 eligible women were r and omly assigned to three treatment groups : placebo ( daily dose of 0 mg isoflavones + 500 mg calcium , n = 67 ) , mid-dose ( 40 mg isoflavones + 500 mg calcium , n = 68 ) ; and high-dose ( 80 mg isoflavones + 500 mg calcium , n = 68 ) . Bone mineral density ( BMD ) and BMC at the whole body , spine , and hip were measured by dual-energy x-ray absorptiometry at baseline and posttreatment after 1 year . YSM , BW , and dietary calcium intake stratified analyses were performed to evaluate whether the associations between isoflavones  supplementation and BMC change rates were varied with these factors . Results : Both univariate and multivariate analyses observed significant favorable effect of isoflavone supplementation on rates of change in BMC at the total hip and trochanter among later postmenopausal women ( > 4 y ) , in women with lower BW ( ≤median , 55.5 kg ) , or among women with lower level of calcium intake ( ≤median , 1095 mg/d ) . Conclusions : The independent effect of soy on the maintenance of hip BMC is more marked in women in later menopause or those with lower BW or calcium intake It is believed that soy isoflavone has much potential effectiveness on the postmenopausal status ; however , the optimal dose for preventing postmenopausal bone loss still remains unclear . This open-labeled , self-controlled pilot study was undertaken to determine the effect of 1-year supplementation of different high dosages of soy isoflavone in postmenopausal Taiwanese women . Forty-three women aged 45 - 67 years were enrolled and r and omly assigned into a control ( C ) , 100 mg/day isoflavone ( IF100 ) and 200 mg/day isoflavone ( IF200 ) groups for 1 year . Dual-energy X-ray absorptiometry and other related biochemical markers of bone metabolism were measured . Results indicated that the decrease in bone mineral density ( BMD ) was significant for lumbar vertebrae L1 - 3 , L1 - 4 and the femur neck in the C group ; surprisingly , the BMD of L1 - 3 was significantly elevated in the IF100 group ; however , there were no consistent responses in the IF200 group . No significant change except loss of the bone mineral content of Ward 's triangle ( P=.003 ) was found in the IF200 group after treatment . The percentage change at L1 - 3 was less ( P=.04 ) in the IF200 group when compared to the IF100 group . A relatively uniform direction of bone formation in exp and ing the weight and area with different rates of change result ed in different BMD changes . Both indicated a change of bone formation patterns with the higher-dose supplement . A protective effect of IF100 on estrogen-related bone loss was observed . A lack of a benefit such as high safety in the IF200 group for 1-year administration was ensured and lacked undesirable side effects The effects of soy protein ( 40 g/d ) containing moderate and higher concentrations of isoflavones on blood lipid profiles , mononuclear cell LDL receptor messenger RNA , and bone mineral density and content were investigated in 66 free-living , hypercholesterolemic , postmenopausal women during a 6-mo , parallel-group , double-blind trial with 3 interventions . After a control period of 14 d , during which subjects followed a National Cholesterol Education Program Step I low-fat , low-cholesterol diet , all subjects were r and omly assigned to 1 of 3 dietary groups : Step I diet with 40 g protein/d obtained from casein and nonfat dry milk ( CNFDM ) , Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein ( ISP56 ) , or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein ( ISP90 ) . Total and regional bone mineral content and density were assessed . Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group ( P < 0.05 ) . HDL cholesterol increased in both ISP56 and ISP90 groups ( P < 0.05 ) . Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM ( P < 0.05 ) . Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group ( P < 0.05 ) . Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women . However , only the higher isoflavone-containing product protected against spinal bone loss Following the results of the Women 's Health Initiative , many women now decline estrogen replacement at the time of menopause and seek natural remedies that would treat menopausal symptoms and prevent bone loss and other long-term consequences of estrogen deficiency , but without adverse effects on the breast , uterus , and cardiovascular system . The results of most soy studies in this population have had limitations because of poor design , small sample size , or short duration . This report describes the study rationale , design , and procedures of the Soy Phytoestrogens As Replacement Estrogen ( SPARE ) study , which was design ed to determine the efficacy of soy isoflavones in preventing spinal bone loss and menopausal symptoms in the initial years of menopause . Women ages 45 to 60 without osteoporosis and within 5 years from menopause were r and omized to receive soy isoflavones 200 mg daily or placebo for 2 years . Participants have yearly measurements of spine and hip bone density , urinary phytoestrogens , and serum lipids , thyroid stimulating hormone , and estradiol . Menopausal symptoms , mood changes , depression , and quality of life are assessed annually . The SPARE study recruited 283 women , 66.1 % were Hispanic white . With a large cohort , long duration , and large isoflavone dose , this trial will provide important , relevant , and currently unavailable information on the benefits of purified soy isoflavones in the prevention of bone loss and menopausal symptoms in the first 5 years of menopause . Given the high proportion of Hispanics participating in the study , the results of this trial will also be applicable to this minority group CONTEXT Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes , but its use has risks . Isoflavones , estrogenlike compounds naturally occurring in plant foods , might confer positive effects with fewer adverse effects . OBJECTIVE To investigate whether soy protein with isoflavones improves cognitive function , bone mineral density , and plasma lipids in postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years , recruited from a population -based sample in the Netherl and s , conducted between April 2000 and September 2001 . INTERVENTION Participants were r and omly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones ( 52 mg genistein , 41 mg daidzein , and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months . MAIN OUTCOME MEASURES Cognitive function was assessed using the following instruments : dementia , Mini-Mental State Examination ; memory , Rey Auditory Verbal Learning Test , immediate recall , delayed recall , and recognition , the Digit Span forward and reversed , and the Doors test ; complex attention tasks , Digit Symbol Substitution and Trailmaking , A1 , A2 , and B ; and verbal skills , Verbal Fluency A and N , animals and occupations , and the Boston Naming Task . Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning . Lipid assessment included lipoprotein(a ) , total cholesterol , low-density lipoprotein , high-density lipoprotein , and triglycerides . RESULTS A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis . Adherence was good ( median plasma genistein levels , 17.2 and 615.1 nmol/L for placebo and soy group , respectively ) . Cognitive function , bone mineral density , or plasma lipids did not differ significantly between the groups after a year . CONCLUSION This double-blind r and omized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function , bone mineral density , or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later OBJECTIVE To investigate the relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density ( BMD ) of Chinese postmenopausal women . METHODS It was a r and omly controlling test for 12 months . The Pvu II and Xba I polymorphisms of ER-alpha gene were detected by using restriction fragment length polymorphisms ( RFLP ) in 691 Chinese postmenopausal women , aged 45 - 65 years . In 497 carriers of definitive Pvu II-Xba I haplotype , 93 subjects were chosen r and omly . BMD was measured by dual energy X-ray absorptiometry ( DXEA ) . According to BMD T score in any skeleton site of 81 subjects at baseline , 29 subjects with T > or = -1.5 were grouped into observation group , and 52 subjects with T < -1.5 were r and omly assigned into two intervention groups and received either a 100 mg soy isoflavone and 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) or 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) . BMD of the whole body , lumber ( L2-L4 ) , and hip were measured at baseline and after 12 months . RESULTS After one year fellow-up , the BMD at L2-L4 , femur neck site and whole body were significantly decreased as compared with those of baseline ( P < 0.05 , change percent of BMD as follows : -3.31 % , -3.09 % , -1.88 % ) in observation group , and the whole body BMD was significantly lower at 12 month than that at baseline in subjects with Px haplotype ( percent change was -2.44 % , P < 0.05 ) , but no difference was found in subjects without Px haplotype . Whole body and femur neck BMD were significantly decreased in both Ca group and Ca + soy isoflavone group , but no significant difference of change percent between two groups . There were no significant changes in L2-L4 and trochanter BMD irrespective of treatment . ER-alpha Px haplotype had no effect on the changes in BMD in both Ca group and Ca + soy isoflavone group . CONCLUSION The rate of bone loss in Chinese postmenopausal women seems to haverelation to ER Px haplotype . Calcium supplementation for 1 year might lower the bone loss rate , but soy isoflavone supplementation for 1 year had notshowu no effects . The effect of supplementation had no relationship with ER Px haplotype CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P<.001 ) . The HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture Animal studies demonstrated that phytoestrogen had a protective effect against  bone loss after ovariectomy . However , data on dietary phytoestrogen intake as well as its relationship with bone mineral density ( BMD ) in human are not available . Six hundred fifty southern Chinese women , aged 19 to 86 yr , were recruited to determine their dietary phytoestrogen intake by a food frequency question naire . BMDs at the lumbar spine and hip region were measured using dual energy x-ray absorptiometry . The subjects were analyzed according to various tertiles of phytoestrogen intake . Among the postmenopausal women ( n = 357 ) , significant differences in the lumbar spine ( L2 - 4 ) BMD ( 0.820 + /- 0.145 vs. 0.771 + /- 0.131 g/cm2 , P < 0.05 ) and Ward 's triangle BMD ( 0.450 + /- 0.151 vs. 0.415 + /- 0.142 g/cm2 ; P < 0.05 ) were found between the highest and lowest intake of isoflavone after adjusting for age , height , weight , years since menopause , smoking , alcohol consumption , HRT usage , and daily calcium intake . Women with the highest intake of isoflavone had significantly lower levels of serum PTH ( 19.38 + /- 14.61 vs. 26.56 + /- 11.19 pg/ml ; P < 0.05 ) , osteocalcin ( 4.95 + /- 3.61 vs. 6.69 + /- 5.05 mg/liter ; P = 0.05 ) , and urinary N-telopeptide ( 34.18 + /- 25.31 vs. 49.66 + /- 41.00 nmol bone collagen equivalents/mmol creatinine ; P < 0.05 ) when compared with those with the lowest intake of isoflavone . No association between dietary phytoestrogen intake and BMDs was seen in the premenopausal women with high endogenous E ( n = 293 ) . In conclusion , postmenopausal women with habitually high intake of dietary isoflavone are associated with higher BMD values at both the spine and hip region . Customarily high isoflavone intake may help to reverse the state of secondary hyperparathyroidism associated with E withdrawal and hence lower the rate of bone turnover in postmenopausal women CONTEXT Genistein aglycone improves bone metabolism in women . However , questions about the long-term safety of genistein on breast as well as its continued efficacy still remain . OBJECTIVE We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy . DESIGN The parent study was a r and omized , double-blind , placebo-controlled trial involving 389 osteopenic , postmenopausal women for 24-months . Subsequently , a subcohort ( 138 patients ) continued therapy for an additional year . PATIENTS AND INTERVENTIONS Participants received 54 mg of genistein aglycone daily ( n = 71 ) or placebo ( n = 67 ) . Both treatment arms received calcium and vitamin D(3 ) in therapeutic doses . MAIN OUTCOMES Mammographic density was assessed at baseline , 24 and 36 months by visual classification scale and digitized quantification . BRCA1 and BRCA2 , sister chromatid exchange , and endometrial thickness were also evaluated . Lumbar spine and femoral neck bone mineral density were also assessed . Secondary outcomes were biochemical levels of bone markers . RESULTS After 36 months , genistein did not significantly change mammographic breast density or endometrial thickness , BRCA1 and BRCA2 expression was preserved , whereas sister chromatid exchange was reduced compared with placebo .  Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo . Genistein also significantly reduced pyridinoline , as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB lig and while increasing bone-specific alkaline phosphatase , IGF-I , and osteoprotegerin levels . There were no differences in discomfort or adverse events between groups . CONCLUSIONS After 3 yr of treatment , genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic , postmenopausal women UNLABELLED Epimedium brevicornum maxim , a nonleguminous medicinal plant , has been found to be rich in phytoestrogen flavonoids . Results from a 24-month r and omized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women , without result ing in a detectable hyperplasia effect on the endometrium . INTRODUCTION We performed a 24-mo r and omized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids ( EPFs ) on BMD , bone turnover biochemical markers , serum estradiol , and endometrial thickness in postmenopausal women . MATERIAL S AND METHODS One hundred healthy late postmenopausal women , with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD , were r and omized into EPF treatment group ( n = 50 ; a daily dose of 60 mg Icariin , 15 mg Daidzein , and 3 mg Genistein ) or placebo control group ( n = 50 ) . All participants received 300 mg element calcium daily . BMD , bone turnover biochemical markers , serum estradiol , and endometrial thickness were measured at baseline and 12 and 24 mo after intervention . RESULTS Eighty-five participants completed the trial . The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated- measures ANOVA ( p = 0.045 for interaction between time and group at femoral neck ; p = 0.006 for interaction between time and group at lumbar spine ) . BMD was found with a decreased tendency in the placebo control group at 12 ( femoral neck : -1.4 % , p = 0.104 ; lumbar spine : -1.7 % , p = 0.019 ) and 24 mo ( femoral neck : -1.8 % , p = 0.048 ; lumbar spine : -2.4 % , p = 0.002 ) , whereas EPF treatment maintained BMD at 12 ( femoral neck : 1.1 % , p = 0.285 ; lumbar spine:1.0 % , p = 0.158 ) and 24 mo ( femoral neck : 1.6 % , p = 0.148 ; lumbar spine : 1.3 % , p = 0.091 ) . The difference in lumbar spine between the two groups was significant at both 12 ( p = 0.044 ) and 24 mo ( p = 0.006 ) , whereas the difference in the femoral neck was marginal at 12 mo ( p = 0.061 ) and significant at 24 mo ( p = 0.008 ) . Levels of bone biochemical markers did not change in the placebo control group . In contrast , EPF intervention significantly decreased levels of deoxypyrdinoline at 12 ( -43 % , p = 0.000 ) and 24 mo ( -39 % , p = 0.000 ) , except for osteocalcin at 12 ( 5.6 % , p = 0.530 ) and 24 mo ( 10.7 % , p = 0.267 ) . A significant difference in deoxypyrdinoline between the two groups was found at both 12 ( p = 0.000 ) and 24 mo ( p = 0.001 ) . Furthermore , neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial . CONCLUSIONS EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without result ing in a detectable hyperplasia effect on the endometrium Background Previous studies show that daily doses of 40–99 mg soy isoflavones produce inconsistent effects on preventing estrogen-related bone loss in postmenopausal women . Aim of the study To examined the bone-sparing effect of isoflavones at a higher dose in early Chinese postmenopausal women . Methods A total of 90 eligible women aged 45–60 years were r and omly assigned to three treatment groups ( 30 subjects/group ) with daily dosages of 0 ( placebo ) , 84 and 126 mg isoflavones for 6 months . Further inclusion criteria included body mass index < 30 kg/m2 and Kuppermann Climacteric Scale > 15 . Bone mineral density ( BMD ) of the spine and hip were measured using dual- energy X-ray absorptiometry at 0 and 6 months . Serum osteocalcin , bone-specific alkaline phosphatase ( BAP ) and urinary deoxypyridinoline were examined at 0 , 3 and 6 months . Results Mean percent changes in BMD at the lumbar spine ( p = 0.114 ) and femoral neck ( p = 0.053 ) increased with the supplementations of soy isoflavones after adjusting for age , years since menopause , body weight and height , dietary intakes of isoflavones , calcium and protein , physical activities and baseline BMD at the relevant sites . We observed significantly dose-dependent linear relationship between the  supplemental isoflavones  and percent changes of BMD at the spine ( p = 0.042 ) and femoral neck ( p = 0.016 ) post-treatment , and urinary total deoxypyridinoline ( p = 0.014 ) at 12 weeks but not at 24 weeks after adjusting for the above factors . No significant difference in percent changes in serum osteocalcin ( p > 0.05 ) and BAP ( p > 0.05 ) was found among the three treatment groups at 12-week and 24-week post-treatment . Conclusion There is a significantly dose-dependent effect of soy isoflavones on attenuating bone loss at the spine and femoral neck possibly via the inhibition of bone resorption in non-obese postmenopausal Chinese women with high Kuppermann Scale We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were r and omized to four groups :  exercise training ( Ex ) ; isoflavone supplementation ( Iso : 165 mg/d [ 105 mg/d aglycone equivalent ] ) ; combined Ex and Iso ( ExIso ) ; and placebo ( control ) . Exercise included resistance training ( 2 days/week ) and walking ( 4 days/week ) . Our primary outcomes were lumbar spine and hip bone mineral density ( BMD ) . Secondary outcomes included hip geometry , tibia and radius speed of sound ( SOS ) , dynamic balance ( 6 m backward t and em walking ) , blood lipids , mammography , and endometrial thickness .  A total of 351 women ( Ex = 86 , Iso = 90 , ExIso = 87 , control = 88 ) were r and omized , with 298 analyzed at 2 years ( Ex = 77 , Iso = 76 , ExIso = 72 , control = 73 ) . There was a significant interaction for total hip BMD ( p < 0.001 ) such that ExIso had a greater rate of decrease ( absolute change [ 95 % confidence interval ] = -0.018 [ -0.024 , -0.012 ] g/cm(2 ) ) than either the Ex or Iso groups alone ( -0.005 [ -0.01 , 0.001 ] and -0.005 [ -0.011 , 0.001 ] g/cm(2 ) , respectively ) . There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS . Exercise groups improved dynamic balance as measured by a decrease in backward t and em walking time over 6 m ( p = 0.017 ) . Isoflavone groups decreased low density lipoproteins ( Iso : -0.20 [ -0.37 , -0.02 ] mmol/L ; ExIso : -0.23 [ -0.40 , -0.06 ] mmol/L ; p = 0.003 ) compared to non-isoflavone groups ( Ex : 0.01 [ -0.16 , 0.18 ] mmol/L ; control : -0.09 [ -0.27 , 0.08 ] mmol/L ) and had lower adverse reports of menopausal symptoms ( 14 % versus 33 % ; p = 0.01 ) compared to non-isoflavone groups . Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms . We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control , but these two interventions interfere with each other when combined . Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms
target: Conclusions : Isoflavone treatments exert a moderately beneficial effect against  estrogen-deficient bone loss in women .
  The effect appears dependent on whether isoflavone treatments are in aglycone form ; we conclude that beneficial effects against bone loss may be enhanced for isoflavone aglycones
background: Background : Age-related estrogen deficiency leads to accelerated bone resorption .
  There is evidence that , through selective estrogen receptor modulation , isoflavones may exert beneficial effects against  estrogen-deficient bone loss .
  Isoflavone aglycones show higher bioavailability than their glycosidic counterparts and thus may have greater potency .
  Objective : To summarize evidence , we executed a systematic review and meta- analysis examining isoflavone therapies and bone mineral density ( BMD ) loss in peri- and postmenopausal women .