Reproductive hormone exposure timing and ischemic heart disease: Complicated answers to a simple question. Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women Characteristics of hormone therapy, cognitive function, and dementia Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. The rationale, design, and baseline characteristics of the Women's Health Initiative Memory Study of Younger Women (WHIMS-Y) The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition. Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis Women’s Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy Hormone therapy and Alzheimer disease dementia Low-fat dietary pattern and change in body-composition traits in the Women's Health Initiative Dietary Modification Trial. Raloxifene reduces risk of vertebral fractures [corrected] in postmenopausal women regardless of prior hormone therapy. Lifestyle intervention and coronary heart disease risk factor changes over 18 months in postmenopausal women: the Women On the Move through Activity and Nutrition (WOMAN study) clinical trial. A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative. Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease. Exercise frequency and calcium intake predict 4-year bone changes in postmenopausal women Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy The Effects of Hormone Therapy Decision Support for Women With Mobility Impairments Effects of hormone therapy on soluble cell adhesion molecules in postmenopausal women with coronary artery disease
Premenopausal women have a relatively lower risk of ischemic heart disease ( IHD )  compared to age matched men and this gender gap narrows after menopause . The observation that the onset of IHD occurs 10 years later in women than it does in men is said to suggest that endogenous reproductive hormones play a protective role . Indeed , animal models and human epidemiological studies suggest that oophorectomy is a risk factor for accelerated IHD . In animal models , hormone therapy ( HT ) has anti-atherosclerotic effects after oophorectomy , HT in the form of oral contraceptives ( OCs ) prevents atherosclerosis in anovulatory cycling women , and large numbers of premenopausal women taking OCs have relative safety from an IHD st and point ( 1 ) . Further , observational epidemiological studies in humans have consistently demonstrated protective effects for IHD among HT users . Such studies are typically performed on relatively younger women where  HT  is prescribed for  vasomotor symptoms during menopausal transition or shortly following menopause . In contrast , clinical trials in older , postmenopausal and often asymptomatic women have demonstrated no overall benefit and early adverse effects when r and omized to a variety of forms of HT ( 1 ) . These data discrepancies have called into question the validity of the reproductive hormone estrogen protection hypothesis , and raise the alternative possibility that  HT efficacy may differ according to the timing of exposure . Stated as a simple question , is the effect of HT on the risk of IHD in relatively young pre- or early menopausal women with vasomotor symptoms , different than it is in older , fully menopausal women ? Data from the Women ’s Ischemia Syndrome Evaluation ( WISE ) , a prospect i ve multi-center NHLBI-sponsored study design ed to explore female-specific pathophysiology in a large sample of women undergoing coronary angiography for suspected IHD ( 2 ) , may shed light on this controversy . These new data , prospect ively obtained using novel methods , including detailed reproductive health question naires , menopausal adjudication algorithms , and quantitative coronary angiography as a measure of atherosclerosis , allow a more precise inspection of this question . However , to answer this simple question we need to first answer others . Specifically , how can we integrate and underst and the findings from the available observational , animal and clinical trial data ? And to interpret these data other questions become relevant : 1 ) How accurately was menopause assessed in prior observational HT studies ? 2 ) Does HT in premenopausal women in the form of OC therapy confirm atherosclerosis benefit ? and 3 ) Does HT in early menopausal women confer reduced atherosclerosis and benefit on the risk of IHD Background —Despite diffuse effects of sex hormones on the cardiovascular system , few prospect i ve studies have examined the relationship of plasma and rogens and estrogens with risk of cardiovascular disease ( CVD ) in postmenopausal women . Methods and Results —A nested case-control study was performed among women in the Women ’s Health Study . Two hundred women who developed CVD were matched 1:1 by age , smoking , and postmenopausal hormone therapy ( HT ) to controls who remained free of CVD . We measured testosterone , estradiol , and sex hormone binding globulin ( SHBG ) levels and calculated free and rogen index ( FAI ) , free estradiol index , and the FAI/free estradiol index ratio .  Results were stratified by HT use . Among HT nonusers , cases had significantly higher and rogen profiles ( higher median FAI and lower SHBG levels ) than controls . After adjustment for age , smoking , use of aspirin , vitamin E , and alcohol , family history of myocardial infa rct ion , and physical activity , nonusers in the lowest SHBG quartile had an OR of 2.25 ( 95 % CI , 1.03 to 4.91 ) for CVD , and there were significant trends across FAI quartiles ( P for trend=0.03 ) . Additional adjustment for body mass index , hypertension , diabetes , and elevated cholesterol eliminated associations with SHBG and FAI . Among women using HT , no significant differences in hormones or SHBG were observed among women who developed CVD and controls . Conclusions —Among HT nonusers , lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events , but this was not independent of body mass index and other cardiovascular risk factors . Estradiol levels were not associated with risk of CVD in  HT  users or nonusers Objectives : To examine the association between hormone therapy ( HT ) and cognitive performance or dementia , focusing on the duration and type of treatment used , as well as the timing of initiation of HT in relation to the menopause . Methods : Women 65 years and older were recruited in France as part of the Three City Study . At baseline and 2- and 4-year follow-up , women were administered a short cognitive test battery and a clinical diagnosis of dementia was made . Detailed information was also gathered relating to current and past HT use . Analysis was adjusted for a number of sociodemographic , behavioral , physical , and mental health variables , as well as APOE ε4 . Results : Among 3,130 naturally postmenopausal women , current HT users performed significantly better than never users  on verbal fluency , working memory , and psychomotor speed . These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial . However , initiation of HT close to the menopause was not associated with better cognition . HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE ε4 . Conclusions : Current hormone therapy ( HT ) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used . We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life . Current HT may decrease the risk of dementia associated with the APOE ε4 allele BACKGROUND Apparently discrepant findings have been reported by the Women 's Health Initiative ( WHI ) trial compared with observational studies of postmenopausal hormone therapy ( HT ) and coronary heart disease ( CHD ) . METHODS We prospect ively examined the relation of HT to CHD , according to timing of hormone initiation relative to age and time since menopause . Participants were postmenopausal women in the Nurses ' Health Study , with follow-up from 1976 to 2000 . Information on hormone use was ascertained in biennial , mailed question naires . We used proportional hazards models to calculate multivariable adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) . We also conducted sensitivity analyses to determine the possible influence of incomplete capture of coronary events occurring shortly after initiation of HT . RESULTS Women beginning HT near menopause had a significantly reduced risk of CHD ( RR = 0.66 , 95 % CI 0.54 - 0.80 for estrogen alone ; RR = 0.72 , 95 % CI 0.56 - 0.92 for estrogen with progestin ) . In the subgroup of women demographically similar to those in the WHI , we found no significant relation between HT and CHD among women who initiated therapy at least 10 years after menopause ( RR = 0.87 , 95 % CI 0.69 - 1.10 for estrogen alone ; RR = 0.90 , 95 % CI 0.62 - 1.29 for estrogen with progestin ) . Among women who began taking hormones at older ages , we also found no relation between current use of estrogen alone and CHD ( for women aged 60 + years , RR = 1.07 , 95 % CI 0.65 - 1.78 ) , although there was a suggestion of possible reduced risk for combined HT ( RR = 0.65 , 95 % CI 0.31 - 1.38 ) . In sensitivity analyses , we found that the incomplete capture of coronary events occurring shortly after initiation of HT could not explain our observation of a reduced risk of coronary disease for current users of HT . CONCLUSIONS These data support the possibility that timing of HT initiation in relation to menopause onset or to age might influence coronary risk The Women 's Health Initiative Memory Study -Younger ( WHIMS-Y ) was design ed to assess the effect of prior r and om assignment to hormone therapy ( HT ) ( conjugated equine estrogen ( CEE ) alone or CEE plus medroxyprogesterone acetate ( MPA ) ) on global cognitive function in younger middle-aged women relative to placebo . WHIMS-Y was an ancillary study to the Women 's Health Initiative ( WHI ) HT trial and enrolled 1361 women who were aged 50 - 55 years and postmenopausal at WHI enrollment . WHIMS-Y will examine whether an average of 5.4 years of HT during early menopause has longer term protective effects on global cognitive function and if these effects vary by regimen , time between menopause and study initiation , and prior use of HT . We present the study rationale and design . We describe enrollment , adherence to assigned WHI therapy , and compare risk factor characteristics of the WHIMS-Y cohort at the time of WHI enrollment to similar aged women in the WHI HT who did not enroll in WHIMS-Y. Challenges of WHIMS-Y include lower than expected and differential enrollment . Strengths of WHIMS-Y include balance in baseline risk factors between treatment groups , st and ardized and masked data collection , and high rates of retention and on-trial adherence and exposure . In addition , the telephone-administered cognitive battery showed adequate construct validity . WHIMS-Y provided an unprecedented chance to examine the hypothesis that HT may have protective effects on cognition in younger postmenopausal women aged 50 - 55 years . Integrated into the WHI , WHIMS-Y optimized the experience of WHI investigators to ensure high retention and excellent quality assurance across sites . This article is part of a Special Issue entitled Hormone Therapy Background For postmenopausal women , the main reason to start hormone therapy ( HT ) is to reduce menopausal symptoms and to improve quality of life ( QOL ) . The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a r and omised trial . A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy ( EPHT ) trial in 1999–2001 . Women were r and omised to blind HT , open-label HT , placebo or non-treatment arm . After one year in the trial , a question naire was mailed and 1359 women ( 75 % ) responded , 686 in the HT arms and 673 in the non-HT arms . Mean age at filling in the question naire was 59.8years . The question naire included Women 's Health Question naire ( WHQ ) to assess menopause specific QOL of middle-aged women together with a 17-item question naire on symptoms related to menopause , a question about painful intercourse , and a question about women 's self-rated health . Results After one year in the trial , fewer women in the HT arms reported hot flashes , trouble sleeping , and sweating on the symptom question naire . According to WHQ , women in the HT arms had fewer vasomotor symptoms , sleep problems , and problems with sexual behaviour , but more menstrual symptoms ;  HT had no effect on depression , somatic symptoms , memory , attractiveness , or anxiety . A smaller proportion of women reported painful intercourse in the HT arms . There were no significant differences between the trial arms in women ’s self-rated subjective health . Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms , other than vasomotor symptoms , among postmenopausal women . WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women Objective : The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy ( HT )  Trials of the Women 's Health Initiative ( WHI ) . Methods : Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a r and om 8.6 % sub sample at years 3 and 6 . The associations with demographic and health characteristics were determined . Results : Sexual activity at baseline was 60.7 % , 44.9 % , and 28.2 % in the 50- to 59- , 60- to 69- , and 70- to 79-year-old age groups , respectively . Most of the participants were satisfied with their current sexual activity ( 63.2 % ) . Of those dissatisfied , 57 % preferred more sexual activity . Vaginal atrophy correlated with sexual inactivity at baseline ( P < 0.001 ) . The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health , lack of satisfaction with quality of life , depression , and loss of partner ( P < 0.001 ) . The strongest predictor of sexual activity at year 1 was sexual activity at baseline ( odds ratio , 96.71 ; 95 % CI , 81.90 - 114.20 ) . A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity ( P = 0.01 ) . Conclusions : Most women in the WHI HT Trials were satisfied with their sexual activity . Of those who were dissatisfied , the majority preferred more , rather than less , sexual activity . Vaginal atrophy at baseline correlated with sexual inactivity , and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1 . HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis . This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction The objective of this study was to examine the effects of estrogen-based hormone therapy ( HT ) on regional cerebral metabolism in postmenopausal women ( mean age = 58 , SD = 5 ) at risk for development of dementia . The prospect i ve clinical trial design included pre- and post-intervention neuroimaging of women r and omized to continue ( HT+ ) or discontinue ( HT− ) therapy following an average of 10 years of use . The primary outcome measure was change in brain metabolism during the subsequent two years , as assessed with  fluorodeoxyglucose-18 positron emission tomography ( FDG-PET ) . Longitudinal FDG-PET data were available for 45 study completers . Results showed that women r and omized to continue HT experienced relative preservation of frontal and parietal cortical metabolism , compared with women r and omized to discontinue HT . Women who discontinued 17-β estradiol (17βE)-based HT , as well as women who continued conjugated equine estrogen (CEE)-based HT , exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical ( PCC ) area . Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins ( with either 17βE or CEE ) . Together , these findings suggest that among postmenopausal subjects at risk for developing dementia , regional cerebral cortical metabolism is relatively preserved for at least two years in women r and omized to continue HT , compared with women r and omized to discontinue HT . In addition , continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC , known to undergo the most significant decline in the earliest stages of Alzheimer 's disease . Trial Registration Clinical Trials.gov Estrogen-only  menopausal hormone therapy ( HT ) increases the risk of endometrial cancer , but less is known about the association with other types of HT . Using Cox proportional hazards regression , the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospect i ve Investigation into Cancer and Nutrition between 1992 and 2000 . After a mean follow-up period of 9 years , 601 incident cases of endometrial cancer were identified . In comparison with never users of  HT  , risk of endometrial cancer was increased among current users of estrogen-only HT ( hazard ratio ( HR ) = 2.52 , 95 % confidence interval ( CI ) : 1.77 , 3.57 ) , tibolone ( HR = 2.96 , 95 % CI : 1.67 , 5.26 ) , and , to a lesser extent , estrogen-plus-progestin HT ( HR = 1.41 , 95 % CI : 1.08 , 1.83 ) , although risks differed according to regimen and type of progestin constituent . The association of HT use with risk was stronger among women who were older , leaner , or had ever smoked cigarettes . The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk . The increased risk associated with tibolone use requires further investigation Objective : To examine whether the effect of postmenopausal hormone therapy ( HT ) on brain volumes in women aged 65–79 years differs depending on type 2 diabetes status during postintervention follow-up of a r and omized controlled clinical trial . Methods : The Women 's Health Initiative r and omized clinical trials assigned women to HT ( 0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate ) or placebo for an average of 5.6 years . A total of 1,402 trial participants underwent brain MRI  2.4 years after the trials ; these were repeated in 699 women 4.7 years later . General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes . Results : Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of −18.6 mL ( 95 % confidence interval [ CI ] −29.6 , −7.6 ) . For women without diabetes , this mean decrement was −0.4 ( 95 % CI −3.8 , 3.0 ) ( interaction p = 0.002 ) . This interaction was evident for total gray matter ( p < 0.001 ) and hippocampal ( p = 0.006 ) volumes . It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications . Conclusions : For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes , prescription of postmenopausal HT is associated with lower gray matter ( total and hippocampal ) volumes . Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women Objective This study aims to present methods and baseline data from the Early versus Late Intervention Trial with Estradiol ( ELITE ) , the only clinical trial design ed to specifically test the timing hypothesis of postmenopausal hormone therapy ( HT ) . The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time since menopause . Methods ELITE is a r and omized , double-blind , placebo-controlled trial with a 2 × 2 factorial design . Six hundred forty-three healthy postmenopausal women without cardiovascular disease were r and omized to oral estradiol or placebo for up to 6 to 7 years according to time since menopause ( < 6 or ≥10 y ) . Carotid artery intima-media thickness ( CIMT ) and cardiac computed tomography  were conducted to determine HT effects on sub clinical atherosclerosis across menopause strata . Results Participants in the early and late postmenopausal strata were well-separated by mean age ( 55.4 vs 65.4 y ) and median time since menopause ( 3.5 vs 14.3 y ) . Expected risk factors ( age , blood pressure , and body mass index ) were associated with CIMT at baseline in both strata . In the early postmenopausal group , but not in the late postmenopausal group , we observed significant associations between CIMT and factors that may play a role in the responsiveness of atherosclerosis progression according to timing of HT initiation . These include low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , sex hormone – binding globulin , and serum total estradiol . Conclusions The ELITE r and omized controlled trial is timely and unique . Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease Objective This study aims to test the added value of calcium and vitamin D ( CaD ) in fracture prevention among women taking postmenopausal hormone therapy ( HT ) . Methods This is a prospect i ve , partial-factorial , r and omized , controlled , double-blind trial among Women ’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years . A total of 27,347 women were r and omized to HT ( 0.625 mg of conjugated estrogens alone , or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily ) , and 36,282 women were r and omized to 1,000 mg of elemental calcium ( carbonate ) plus 400 IU of vitamin D3 daily , each compared with placebo .  A total of 16,089 women participated in both arms . The predefined outcomes were adjudicated hip fractures and measured bone mineral density . Results Interaction between HT and CaD on hip fracture ( P interaction = 0.01 ) was shown . The effect of CaD  was stronger among women assigned to HT ( hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.38 - 0.93 ) than among women assigned to placebo ( HR , 1.20 ; 95 % CI , 0.85 - 1.69 ) . The effect of HT on hip fracture was stronger among women assigned to active CaD ( HR , 0.43 ; 95 % CI , 0.28 - 0.66 ) than among women assigned to placebo ( HR , 0.87 ; 95 % CI , 0.60 - 1.26 ) . CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake . There was no interaction between HT and  CaD  on change in hip or spine bone mineral density .  Conclusions Postmenopausal women at normal risk for hip fracture who are on CaD supplementation  experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake Objectives : Observational studies suggest reduced risk of Alzheimer disease ( AD ) in users of hormone therapy ( HT )  , but trials show higher risk . We examined whether the association of HT with AD varies with timing or type of HT use . Methods : Between 1995 and 2006 , the population -based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT .  During this interval , 176 women developed incident AD . Cox proportional hazard models evaluated the association of HT use with AD , overall and in relation to timing , duration of use , and type ( opposed vs unopposed ) of HT . Results : Women who used any type of HT within 5 years of menopause had 30 % less risk of AD ( 95 % confidence interval 0.49–0.99 ) , especially if use was for 10 or more years . By contrast , AD risk was not reduced among those who had initiated HT 5 or more years after menopause . Instead , rates were increased among those who began “ opposed ” estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline ( adjusted hazard ratio 1.93 ; 95 % confidence interval 0.94–3.96 ) . This last hazard ratio was similar to the ratio of 2.05 reported in r and omized trial participants assigned to opposed HT . Conclusions : Association of HT use and risk of AD may depend on timing of use . Although possibly beneficial if taken during a critical window near menopause , HT ( especially opposed compounds ) initiated in later life may be associated with increased risk . The relation of AD risk to timing and type of HT deserves further study BACKGROUND The Women 's Health Initiative Dietary Modification ( DM ) Trial was a r and omized controlled trial that compared the effects of a low-fat ( ≤20 % of total energy ) or a usual diet in relation to chronic disease risk in postmenopausal women . OBJECTIVE We characterized long-term body-composition changes associated with the DM trial and potential modifiers of these associations . DESIGN In the DM trial , 48,835 women aged 50 - 79 y were r and omly assigned to intervention ( 40 % ) or comparison ( 60 % ) groups . We studied a subset with whole-body dual-energy X-ray absorptiometry scans at baseline and during follow-up . Changes in fat mass ( FM ) , lean mass ( LM ) , and percentage body fat between the intervention ( n = 1580 ) and comparison ( n = 2731 ) groups at years 1 , 3 , and 6 were compared . By using generalized estimating equations , we calculated overall differences between groups and tested for interactions with age , diabetes , race-ethnicity ( white , black , and Hispanic ) , body mass index ( BMI ) , and hormone therapy ( HT ) . RESULTS The intervention women experienced significantly greater reductions in percentage body fat , FM , and LM at years 1 and 3 than did women in the comparison group ( all P < 0.05 ) . At year 6 , only the FM change was significantly different between groups . Overall , the intervention was associated with reductions in percentage body fat ( -0.8 % ; 95 % CI : -1.0 % , -0.6 % ) , FM ( -1.1 kg ; 95 % CI : -1.3 , -0.8 kg ) , and LM ( -0.17 kg ; 95 % CI : -0.28 , -0.06 kg ) during follow-up ( all P < 0.003 ) . Intervention associations varied by race-ethnicity , BMI , diabetes , and HT and remained significant after adjustment for physical activity . CONCLUSION This intervention was associated with modest long-term body-composition changes ; the findings were more robust in years 1 and 3 . This trial was registered at clinical trials.gov as NCT00000611 OBJECTIVE We examined whether past use of hormone therapy influences the effects of raloxifene on the risk of new vertebral fracture , cardiovascular events , or breast cancer . STUDY DESIGN The Multiple Outcomes of Raloxifene Evaluation ( MORE ) trial examined vertebral fracture incidence as the primary endpoint , breast cancer incidence as a secondary endpoint . Cardiovascular events were collected as secondary safety endpoints . POPULATION The MORE trial enrolled 7705 postmenopausal women . Of the 7682 women who reported their previous HT use status , 29 % used HT before screening . OUTCOMES MEASURED Separate logistic regression models analyzed the relationships between prior HT use and the risk of vertebral fracture , cardiovascular events , or breast cancer . Interaction terms with P<.10 were considered to be statistically significant . Confidence intervals for relative risks ( RR ) were calculated using the Mantel-Haenszel method . RESULTS Raloxifene 60 mg/d , the clinical ly approved dose for osteoporosis prevention and treatment , reduced the risk of vertebral fractures by 54 % ( RR=0.46 ) and 29 % ( RR=0.71 ) in women with and without prior HT use , respectively ( interaction P=.05 ) . A lower incidence of invasive breast cancer in women with prior HT use ( RR=0.23 ) and in women without prior HT use [ RR=0.31 ; interaction P=.60 ] was observed in women receiving raloxifene ( pooled doses ) . Irrespective of prior HT use , women treated with raloxifene ( pooled doses ) had no change in incidence of cardiovascular events ( interaction P=.56 ) . CONCLUSIONS The risk of vertebral fractures was lower in women treated with raloxifene , regardless of prior HT use , but there was a suggestion that the effect was greater in women who had used HT . Women r and omized to receive raloxifene exhibited a decreased incidence of invasive breast cancer , compared with women receiving placebo . No change occurred in the incidence of cardiovascular events , regardless of prior HT use OBJECTIVES In this paper , we present the results of changes in risk factors by use of hormone therapy ( HT ) at 18 months in the Women On the Move through Activity and Nutrition ( WOMAN ) r and omized trial . METHODS The trial was design ed to test the hypothesis that aggressive dietary changes and increased physical activity to reduce weight , waist circumference ( WC ) , glucose , insulin , and lipoproteins would reduce progression of sub clinical atherosclerosis , carotid intimal media thickness and plaque , coronary artery calcification , and pulse wave velocity ( PWV ) . The study focused on postmenopausal women ( n = 508 ) , mean age of 57 , who were r and omized to the Lifestyle Change ( LC ) or Health Education ( HE ) group .  RESULTS At 18 months of follow-up , there was significant , 17 lb , weight loss and 10 cm WC decrease in the LC group . There were significant differences in changes in low-density lipoprotein cholesterol ( LDL-C ) , insulin , glucose , large LDL , and LDL particles between the LC and HE groups . Risk factor changes were greater for women in the LC who lost a significant amount of weight ( > or=18.8 lb ) . Participants at 18 months were subdivided into women who had stayed on HT , 125 ( 28 % ) ; stopped HT after r and omization , 145 ( 33 % ) ; and not on HT at baseline but stopped an average of 7 months prior to r and omization , 173 ( 39 % ) . Weight loss in the LC was similar for all three groups , but LDL lipoprotein response was better for women who stopped HT after r and omization or were not on HT at baseline . CONCLUSIONS The trial has been successful in increasing exercise and diet changes and reduction in weight and WC and variables related to metabolic syndrome Objective : The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy ( EPT ) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation . A secondary aim was to evaluate whether health-related quality of life ( HRQoL ) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT . Methods : Eighty-one postmenopausal women undergoing EPT because of hot flashes were r and omized to tapering down or abrupt discontinuation of EPT .  Vasomotor symptoms were recorded in self-registered diaries , and resumption of hormone therapy ( HT ) was asked for at every follow-up . The Psychological General Well-being Index was used to assess HRQoL. Results : Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up . About every other woman had resumed HT within 1 year . Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT . Conclusions : Women who initiate EPT  because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used , abrupt or taper down . Because , in addition to severity of flashes , decreased well-being was the main predictor of the risk to resume HT , it seems important to also discuss quality of life in parallel with efforts to discontinue HT BACKGROUND Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass . OBJECTIVE This study cross-sectionally examined whether higher dietary intakes , total intakes , and serum concentrations of antioxidants may be associated with higher  bone mineral density ( BMD ) . DESIGN Total hip ( and subregions ) , spine , and total-body BMDs were measured in 11,068 women aged 50 - 79 y enrolled in the Women 's Health Initiative Observational Study and Clinical Trial at 3 clinics .  Antioxidant intakes from diet ( vitamin A , retinol , beta-carotene , vitamin C , vitamin E , and selenium ) were estimated by using a self-reported food-frequency question naire . Antioxidants from supplements were estimated with an interviewer-administered question naire . A r and om subset ( n = 379 ) had serum concentrations of retinol , carotenoids , and tocopherols measured . RESULTS After adjustment for important BMD-related covariates , increasing intakes of antioxidants were not independently associated with BMD . A significant interaction effect was observed between intake of total vitamin C  ( lower three-fourths compared with highest one-fourth ) and use of  hormone therapy ( HT ) ( P < 0.01 ) . The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body ( P < 0.045 ) , spine ( P = 0.03 ) , and total-hip BMDs ( P = 0.029 ) . CONCLUSIONS Our results do not support independent associations between dietary intake , total intake , or serum concentrations of antioxidants and BMD in women participating in the Women 's Health Initiative . The extent to which HT use may interact with  vitamin C intake and BMD warrants further exploration OBJECTIVE Use of estrogen-based hormone therapy ( HT ) as a protection from cognitive decline and Alzheimer disease ( AD ) is controversial , although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations . Little is known regarding specific population s of women who may derive benefit from HT . METHODS Women with heightened risk for AD ( aged 49 - 69 ) , all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset , underwent  cognitive assessment  followed by r and omization to continue or discontinue HT . Assessment s were repeated at 2 years after r and omization . RESULTS Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention , working memory , and processing speed measures . Women who used 17β-estradiol versus conjugated equine estrogen , whether r and omized to continue or discontinue HT , showed better verbal memory performance at the 2-year follow-up assessment . An interaction was also found with HT r and omization and family history of AD in a first-degree relative . All female offspring of patients with AD declined in verbal memory ; however , women who continued HT declined less than women who discontinued HT . Women without a first-degree relative with AD showed verbal memory improvement ( likely because of practice effects ) with continuance and declined with discontinuance of HT . CONCLUSION Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset The aim of this study was to examine the association of exercise frequency and calcium intake ( CI ) with change in regional and total bone mineral density ( BMD ) in a group of postmenopausal women completing 4 years of progressive strength training . One hundred sixty-seven calcium-supplemented ( 800 mg/day ) sedentary women ( 56.1±4.5 years ) r and omized to a progressive strength training exercise program or to control were followed for 4 years . Fifty-four percent of the women were using hormone therapy ( HT ) at baseline . At 1 year , controls were permitted to begin the exercise program ( crossovers ) . The final sample included 23 controls , 55 crossovers , and 89 r and omized exercisers . Exercisers were instructed to complete two sets of six to eight repetitions of exercises at 70–80 % of one repetition maximum , three times weekly . BMD was measured at baseline and thereafter annually using dual-energy X-ray absorptiometry . Four-year percentage exercise frequency ( ExFreq ) averaged 26.8%±20.1 % for crossovers ( including the first year at 0 % ) , and 50.4%±26.7 % for exercisers . Four-year total CI averaged 1,635±367 mg/day and supplemental calcium intake , 711±174 mg/day . In adjusted multiple linear regression models , ExFreq was positively and significantly related to changes in femur trochanter ( FT ) and neck ( FN ) , lumbar spine ( LS ) , and total body ( TB ) BMD . Among HT  users , FT BMD increased 1.5 % , and FN and LS BMD , 1.2 % ( p < 0.01 ) for each st and ard deviation ( SD ) of percentage ExFreq ( 29.5 % or 0.9 days/week ) . HT non-users gained 1.9 % and 2.3 % BMD at FT and FN , respectively , ( p < 0.05 ) for every SD of CI . The significant , positive , association between BMD change and ExFreq supports the long-term usefulness of strength training exercise for the prevention of osteoporosis in postmenopausal women , especially HT users . The positive relationship of CI to change in BMD among postmenopausal women not using HT  has clinical implication s in light of recent evidence of an increased health risk associated with HT Introduction Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy ( HT ) . We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes . Methods Healthy , non-smoking freshly postmenopausal women ( n = 150 ) with no previous HT use were studied . Seventy-two women reported intolerable hot flushes ( ≥7 moderate/severe episodes/day ) and 78 women tolerable hot flushes ( ≤3 mild episodes/day ) . The participants were treated in r and omized order with either transdermal estradiol gel ( 1 mg ) , oral estradiol valerate ( 2 mg ) with or without medroxyprogesterone acetate ( 5 mg ) , or placebo for 6 months . Treatment-induced changes in lipids , lipoproteins , apolipoproteins , sex hormone binding globulin ( SHBG ) and high-sensitivity C-reactive protein were compared . The trial is registered in the US National Institutes of Health Clinical Research Registry ( no. NCT00668603 ) . Results Pretreatment hot flush status was not related to the responses of these markers to different forms of HT . However , when all active regimens were evaluated together as a post-hoc analysis , 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes . Furthermore , in women with intolerable hot flushes and with HT use , the increases in SHBG ( Spearman 's rho = − 0.570 , p < 0.001 ) were related to the reductions in hot flushes during the use of HT . Conclusions Hot flushes appear to be no significant determinant for the responses of vascular  markers to HT use Deciding about hormone therapy ( HT ) use is particularly complex for women with mobility impairments . While HT controls menopausal symptoms , the potential increased risk of blood clots result ing from physical inactivity can contraindicate HT use . These women , therefore , may benefit from interventions to help them tailor st and ard information about HT . We r and omly assigned women to receive either a tailored decision support intervention or st and ard menopausal information . Both groups ( n = 176 ) significantly decreased their decisional conflict and uncertainty and increased knowledge after receiving the treatment material s. We interpret the findings in the context of limited medical information about HT for women with disabilities Objective : Although observational studies showed an apparent lower ischemic coronary disease risk in postmenopausal women receiving hormone therapy ( HT )  , r and omized clinical trials in postmenopausal women showed an increase in ischemic cardiovascular events . Soluble cell adhesion molecules have been associated with cardiovascular risk factors and events . HT reduces circulating levels of soluble cell adhesion molecules in healthy postmenopausal women , but its effects in postmenopausal women with coronary artery disease are less clear . We assessed the effect of HT on soluble cell adhesion molecules in the Estrogen Replacement and Atherosclerosis trial . Design : The Estrogen Replacement and Atherosclerosis trial was a double-blind , placebo-controlled study that r and omized 309 postmenopausal women ( mean age , 65.8 y ) to daily unopposed estrogen ( conjugated estrogens 0.625 mg ) , estrogen plus 2.5 mg of medroxyprogesterone acetate , or placebo  , with a mean follow-up period of 3.2 years . Soluble intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , and E-selectin were measured in serum obtained from participants at baseline and after 12 months of follow-up . Results : Of the 265 women with complete data , 87 women were assigned to unopposed estrogen , 88 women to estrogen plus medroxyprogesterone acetate , and 90 women to placebo . Compared with placebo , 12 months of HT ( n = 175 ) was associated with reductions in soluble intercellular adhesion molecule-1 ( 25.6 ± 4.7 vs 10.6 ± 6.4ng/mL , P = 0.06 ) , soluble vascular cell adhesion molecule-1 ( 80.2± 10.6 vs 28.8 ± 14.7 ng/mL , P = 0.005 ) , and E-selectin ( 8.8 ± 0.9 vs −1.1 ± 1.2 ng/mL , P < 0.001 ) . Conclusions : Twelve months of HT in postmenopausal women with established coronary artery disease was associated with reductions in serum markers of endothelial cell activation/injury such as soluble intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , and E-selectin
Conclusions and Relevance This systematic review and meta- analysis did not show a significant beneficial or detrimental association of HT with muscle mass .
Importance Hormone therapy ( HT ) has been suggested for protection against age-related muscle weakness in women .
However , the potential for HT-associated health risks necessitates a better underst and ing of the direction and magnitude of the association between HT and health outcomes , such as lean body mass ( LBM ) .
Objective To determine whether HT was associated with reduced LBM loss compared with not receiving HT  among postmenopausal women aged 50 years and older .