Managing menopause. Raloxifene reduces risk of vertebral fractures [corrected] in postmenopausal women regardless of prior hormone therapy. Characteristics of hormone therapy, cognitive function, and dementia Aerobic exercise as a treatment for vasomotor menopausal symptoms: randomised controlled trial protocol. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial A Prospective, Observational Study of Postmenopausal Hormone Therapy and Primary Prevention of Cardiovascular Disease Reproductive hormone exposure timing and ischemic heart disease: Complicated answers to a simple question. Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. Long-Term Prevention with Hormone-Replacement Therapy after the Menopause: Which Women should be Targeted? Epidemiology of risk factors and symptoms associated with menopause in Spanish women. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial Hormone therapy in menopausal women with cognitive complaints The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy NIH asks participants in Women's Health Initiative estrogen-alone study to stop study pills, begin follow-up phase. Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia Effects of hormone therapy on depressive symptoms and cognitive functions in women with Alzheimer disease: a 12 month randomized, double-blind, placebo-controlled study of low-dose estradiol and norethisterone. Estrogen + progestin therapy and cognition: a randomized placebo-controlled double-blind study. Hormone therapy and Alzheimer disease dementia Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition.
OBJECTIVE To provide up date d guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor or urogenital symptoms and on considerations related to cardiovascular disease , breast cancer , urogynaecology , and sexuality . OUTCOMES Lifestyle interventions , prescription medications , and complementary and alternative therapies are presented according to their efficacy in the treatment of menopausal symptoms . Counselling and therapeutic strategies for sexuality concerns in the peri- and postmenopausal years are review ed . Approaches to the identification and evaluation of women at high risk of osteoporosis , along with options for prevention and treatment , are presented in the companion osteoporosis guideline . EVIDENCE Published literature was retrieved through search es of PubMed and The Cochrane Library in August and September 2012 with the use of appropriate controlled vocabulary ( e.g. , hormone therapy , menopause , cardiovascular diseases , and sexual function ) and key words ( e.g. , hormone therapy , perimenopause , heart disease , and sexuality ) . Results were restricted to clinical practice guidelines , systematic review s , r and omized control trials/controlled clinical trials , and observational studies . Results were limited to publication date s of 2009 onwards and to material in English or French . Search es were up date d on a regular basis and incorporated in the guideline until January 5 , 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology assessment -related agencies , national and international medical specialty societies , and clinical practice guideline collection 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 : 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 Evidence suggests that a high proportion of perimenopausal and postmenopausal women experience vasomotor symptoms ( hot flushes/night sweats ) that can be severe and disruptive and which are the principal reason for seeking medical intervention . Hormone therapy ( HT ) is known to be an effective treatment for troublesome hot flushes/night sweats but research has raised questions about the safety of HT and there have been negative high profile media reports about its use . Consequently many women are seeking alternatives and exercise might be one such option but there is a lack of high quality evidence on its effectiveness . AIMS This RCT initially aims to investigate the feasibility/acceptability of two exercise interventions identified from our previous preference study in 165 women , and if found to be feasible/acceptable , continue to recruit sufficient women ( n=261 ) to examine the effect of these interventions on hot flushes/night sweats and other outcomes relevant to menopausal women . METHOD We aim to recruit inactive perimenopausal and menopausal symptomatic women not using HT and r and omise them to one of two exercise interventions or usual care for six months . RESULTS We will assess outcomes at baseline and 6 and 12 months from r and omisation . CONCLUSION We hope this RCT will contribute towards increasing the evidence regarding the question of whether exercise is an effective treatment for vasomotor symptoms in women not taking HT Objective To assess the long term risks and benefits of hormone replacement therapy ( combined hormone therapy versus placebo , and oestrogen alone versus combined hormone therapy ) . Design Multicentre , r and omised , placebo controlled , double blind trial . Setting General practice s in UK ( 384 ) , Australia ( 91 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 years at r and omisation . At early closure of the trial , 56 583 had been screened , 8980 entered run-in , and 5692 ( 26 % of target of 22 300 ) started treatment . Interventions Oestrogen only therapy ( conjugated equine oestrogens 0.625 mg orally daily ) or combined hormone therapy ( conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ) . Ten years of treatment planned . Main outcome measures Primary outcomes : major cardiovascular disease , osteoporotic fractures , and breast cancer . Secondary outcomes : other cancers , death from all causes , venous thromboembolism , cerebrovascular disease , dementia , and quality of life . Results The trial was prematurely closed during recruitment , after a median follow-up of 11.9 months ( interquartile range 7.1 - 19.6 , total 6498 women years ) in those enrolled , after the publication of early results from the women 's health initiative study . The mean age of r and omised women was 62.8 ( SD 4.8 ) years . When combined hormone therapy ( n=2196 ) was compared with placebo ( n=2189 ) , there was a significant increase in the number of major cardiovascular events ( 7 v 0 , P=0.016 ) and venous thromboembolisms ( 22 v 3 , hazard ratio 7.36 ( 95 % CI 2.20 to 24.60 ) ) . There were no statistically significant differences in numbers of breast or other cancers ( 22 v 25 , hazard ratio 0.88 ( 0.49 to 1.56 ) ) , cerebrovascular events ( 14 v 19 , 0.73 ( 0.37 to 1.46 ) ) , fractures ( 40 v 58 , 0.69 ( 0.46 to 1.03 ) ) , and overall deaths ( 8 v 5 , 1.60 ( 0.52 to 4.89 ) ) . Comparison of combined hormone therapy ( n=815 ) versus oestrogen therapy ( n=826 ) outcomes revealed no significant differences . Conclusions Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause . The results are consistent with the findings of the women 's health initiative study and secondary prevention studies . Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause , when the effect may be different . Trial registration Current Controlled Trials IS RCT N 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 Whether to take hormone therapy is one of the most difficult medical decisions that healthy postmenopausal women face . The apparent coronary benefits ( 1 ) of hormone use are an important part of that decision . Although the data appear consistent in suggesting long-term coronary benefits , the Heart and Estrogen/progestin Replacement Study ( 2 ) showed an increased risk for coronary events during the first year of therapy in women with existing heart disease ; we also found such an elevated risk in an examination of secondary prevention in the Nurses ' Health Study ( 3 ) . More recently , a report from the Women 's Health Initiative , an ongoing r and omized clinical trial of hormone therapy for primary prevention of cardiovascular disease , suggested similar findings in healthy women ( National Institutes of Health . Press release ) . However , additional data on short-term effects of hormone use in women without previous cardiovascular disease are sparse . Many further questions also remain . Among them is the cardiovascular effect of daily doses lower than the st and ard 0.625 mg of oral conjugated estrogen . Recent studies suggest that lower doses of hormone therapy provide bone benefits ( 4 ) and , compared with higher doses , might decrease the risk for thromboembolism ( 5 ) and reduce endometrial hyperplasia ( 4 ) . However , few data are currently available on the relation between low-dose estrogen and primary prevention of heart disease and stroke . In an earlier report , we examined the relation between postmenopausal hormone therapy and primary prevention of cardiovascular disease based on 16 years of follow-up from the Nurses ' Health Study ( 6 ) . In the current analysis , we have almost 50 % more follow-up time among women taking daily doses less than 0.625 mg and more than 800 additional cases of cardiovascular disease , allowing more precise assessment of specific associations . Thus , we now report on the relation among  low-dose estrogen , short-term hormone use , and cardiovascular events in 70 533 postmenopausal women with no previous cardiovascular disease who were followed for up to 20 years . We also provide additional information on the effects of estrogen combined with progestin . Methods The Nurses ' Health Study Cohort The Nurses ' Health Study began in 1976 when 121 700 female nurses 30 to 55 years of age completed a mailed question naire about their postmenopausal hormone use and medical history , including cardiovascular disease and its risk factors . We up date information with biennial follow-up question naires . Dietary and physical activity question naires were added in 1980 . Cohort follow-up is greater than 90 % . Ascertainment of Hormone Use In 1976 , women were asked about use and duration of hormone therapy after menopause . Beginning in 1978 , we collected information on type of hormones taken , and starting in 1980 , we asked about the dose of oral conjugated estrogen . All information is up date d biennially . Identification of Cardiovascular Disease We identified first occurrences of nonfatal myocardial infa rct ion , fatal coronary disease , and fatal and nonfatal stroke between the return of the 1976 question naire and 1 June 1996 . Nurses who reported a nonfatal infa rct ion or stroke were asked for permission to review their medical records . Nonfatal myocardial infa rct ions were confirmed by hospital records if they met World Health Organization criteria ( 7 ) ( symptoms plus either elevated levels of cardiac enzymes or diagnostic electrocardiograms ) . Infa rct ions that required hospitalization and were corroborated by interview or letter but for which medical records were unobtainable were included as probable . Infa rct ions of indeterminate age discovered on routine examination were excluded . Nonfatal strokes were confirmed by review of medical records if they were characterized by a typical neurologic deficit , were rapid in onset , lasted at least 24 hours , and met the criteria of the National Survey of Stroke ( 8) . We classified strokes as ischemic ( thrombotic or embolic occlusion of a cerebral artery ) , subarachnoid hemorrhage , or intraparenchymal hemorrhage . We excluded subdural hematomas and strokes caused by infection or neoplasia . Strokes that required hospitalization and were corroborated by letter or interview but for which medical records were unavailable were included as probable . Most deaths were reported by the participants ' families . We search ed the National Death Index to identify deaths among nonrespondents to each 2-year question naire ; mortality follow-up was more than 98 % complete ( 9 ) . For all deaths possibly attributable to cardiovascular causes , we requested permission from relatives ( subject to state regulations ) to review the medical records . Deaths were considered to be due to coronary disease if medical records or autopsy findings confirmed a fatal myocardial infa rct ion . We also included coronary disease listed on the death certificate as the underlying cause without another , more plausible cause , if the nurse was known ( from hospital records , family , or other sources ) to have had coronary disease before death . In no case was the cause listed on the death certificate used as the sole criterion for coronary death . Sudden death within 1 hour of the onset of symptoms in participants with no other plausible cause of death besides coronary disease was also included . Fatal strokes were documented by autopsy or hospital records or if stroke was listed as the underlying cause on the death certificate . The category of major coronary heart disease combines nonfatal myocardial infa rct ion and coronary death ; similarly , total stroke includes nonfatal and fatal cases . The category of combined cardiovascular disease includes major coronary heart disease and stroke . Confirmed and probable cases in each category were analyzed together ( 80 % of major coronary events and 73 % of strokes were confirmed ) . In this and previous analyses ( 6 ) , results for probable cases were similar to those for confirmed cases . The investigators conducted all interviews and record review s without knowledge of participants ' hormone use status . Population for Analysis Women who reported stroke , myocardial infa rct ion , angina , coronary revascularization , or cancer ( except nonmelanoma skin cancer ) on the 1976 question naire were excluded because their disease may have caused them to alter their hormone use . Similarly , women who reported such diagnoses on a subsequent question naire were excluded from further analysis . Thus , at the start of each 2-year interval , the base population included no women reporting these diagnoses . Our own studies ( 6 , 10 ) and other studies ( 11 ) have suggested that hormone therapy may differentially affect incident and fatal strokes ; thus , we separately examined deaths due to stroke . In these analyses , we excluded women with cancer and cardiovascular disease at baseline but did not up date the exclusions because the women who develop cardiovascular disease during follow-up are those most likely to die of stroke . We classified women as postmenopausal from the time of natural menopause or hysterectomy with bilateral oophorectomy .  Women who underwent hysterectomy without bilateral oophorectomy  were considered postmenopausal when they reached the age at which natural menopause had occurred in 90 % of the cohort ( 54 years for smokers and 56 years for nonsmokers ) . In this cohort , the women 's reports of age at menopause ( 12 ) and type of menopause ( 13 ) were highly accurate . In 1976 , 21 947 postmenopausal women entered the analysis , and 48 586 women were added during follow-up as they became postmenopausal , for a total of 70 533 participants ; 808 825 person-years of follow-up were accrued from 1976 to 1996 . Statistical Analysis For each participant , person-months were allocated to hormone categories according to the 1976 data and were up date d every 2 years ( for estrogen dose , follow-up began in 1980 ) . For analyses of type of hormone therapy , we assigned the regimen reported on the 1978 question naire to women who reported hormone use in 1976 . Analyses of type of hormone therapy were limited to users of oral conjugated estrogen with or without oral medroxyprogesterone acetate  , since these were the most common hormone regimens . If no data were available on hormones in a given time period , women were assigned to a missing category for that time period . To maintain the prospect i ve nature of the study , hormone use ( including duration ) during each 2-year period was established from women 's reports at the start of the period ; thus , we probably underestimate duration of use by an average of 1 year . Follow-up for a participant ended at the first diagnosis of cardiovascular disease , death , or 1 June 1996 , whichever came first . The primary analysis is based on incidence rates for which person-months of follow-up were used as the denominator . We used relative risk as the measure of association , defined as the incidence of cardiovascular events among women in various categories of hormone use divided by the incidence among women who never used hormones . We computed age-specific rates by using 5-year categories ( 14 ) and age-adjusted relative risks by using MantelHaenszel rate ratios ( 15 ) with 95 % CIs ( 16 ) . We used pooled logistic regression  across the ten 2-year time periods to adjust simultaneously for potential confounding factors ( 17 ) . In this approach , independent blocks of person-time are pooled for regression analysis , and time-varying covariates are readily accommo date d by assigning successive blocks of person-time to the covariate values at the start of each follow-up cycle . The dependence of the incidence rates on time is modeled nonparametrically with indicator variables . Simulation studies have established the asymptotic equivalence of pooled logistic regression to Cox regression with time-dependent covariates ( 18 ) . The necessary conditions for this equivalence include relatively short time intervals and small probability of the outcome during each interval , both 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 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 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 For decades , hormone-replacement therapy ( HRT ) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency . Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherogenesis and coronary heart disease ( CHD ) in women after the menopause . However , the fact that these promising results were not translated into lower incidences of CHD events in hormone-treated women compared with placebo in subsequent , large , r and omized studies of healthy subjects as well as women with known CHD raised a very intense debate concerning the safety of HRT in terms of cardiovascular risk . A critical mass of data points toward a protective influence of HRT on cardiovascular disease end points in early postmenopausal women , but increased harm in elderly women , especially those with abdominal adiposity or metabolic syndrome . Once the quasi-hysterical reaction to the largest of the r and omized studies ( the Women 's Health Initiative ) has abated , a future strategy should be to concentrate on identifying those relatively few individuals who are not suitable for HRT , as HRT still remains the most thoroughly investigated pharmacological prevention strategy of osteoporosis OBJECTIVES ( 1 ) To assess the prevalence of risk factors for osteoporosis and cardiovascular disease and the prevalence and severity of the appearance of menopausal symptoms among Spanish menopausal women . ( 2 ) To identify the main factors responsible for this severity . ( 3 ) To detect symptom differences between perimenopausal and postmenopausal women . METHODS Cross-sectional descriptive study encompassing women aged 45 - 65 years in the whole Spanish territory . The study population sample was collected through r and om sampling . A total of 10,514 women were included . The sociodemographic , medical history and lifestyle data were assessed by means of a survey . The Kupperman scale was used to assess the severity of menopausal symptoms . RESULTS The prevalence of risk factors for osteoporosis and cardiovascular disease were 67.6 % and 74.8 % , respectively . The most common risk factors were physical inactivity ( 53.6 % ) , obesity ( 44.3 % ) , arterial hypertension ( 36.6 % ) , hypercholesterolemia ( 31.4 % ) , low calcium intake ( 30.1 % ) and smoking ( 28.7 % ) . The predominant symptoms experienced by menopausal women were hot flushes ( 51.4 % ) , insomnia ( 45.7 % ) and irritability ( 42.2 % ) . These were severe in 3.3 % of the sample , moderate in 27.3 % , mild in 24.6 % while 44.8 % had no symptoms . The prevalence of joint pain ( 40.1 % ) and depressive mood ( 40 % ) was higher in perimenopausal than in postmenopausal women . Logistic regression analysis showed that there were differences for age , BMI , smoking , social class and poor consumption of dairy products in the severity of menopausal symptoms . CONCLUSIONS A high prevalence of risk factors for osteoporosis and cardiovascular disease was observed in our study . The main factors contributing to more severe menopausal symptoms were age , BMI , smoking social class and poor consumption of dairy products . In general , postmenopausal women presented significantly higher rates of menopausal symptoms when compared to perimenopausal 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 Background At the time of feasibility work and final design of the trial there was no r and omised control trial evidence for the long-term risks and benefits of hormone replacement therapy . Observational studies had suggested that long term use of estrogen was likely to be associated , amongst other things , with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer . Concomitant use of progestogens had been shown to protect against endometrial cancer , but there were few data showing how progestogen might affect estrogen actions on other conditions . Disease specific risks from observational studies suggested that , overall , long-term HRT was likely to be beneficial . Several studies showed that mortality from all causes was lower in HRT users than in non-users . Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women . The WISDOM trial was design ed to compare combined estrogen and progestogen versus placebo , and estrogen alone versus combined estrogen and progestogen . During the development of WISDOM the Women 's Health Initiative trial was design ed , funded and started in the US . Design R and omised , placebo , controlled , trial . Methods The trial was set in general practice s in the UK ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . In these practice s 284175 women aged 50–69 years were registered with 226282 potentially eligible . We sought to r and omise 22300 postmenopausal women aged 50 – 69 and treat for ten years . The interventions were : conjugated equine estrogens , 0.625 mg orally daily ; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ; matched placebo . Primary outcome measures were : major cardiovascular disease , osteoporotic fractures , breast cancer and dementia . Secondary outcomes were : other cancers , all cause death , venous thromboembolism and cerebro-vascular disease . Results The trial was prematurely closed during recruitment following publication of early results from the Women 's Health Initiative . At the time of closure , 56583 had been screened , 8980 entered run-in , and 5694 ( 26 % of target of 22,300 ) r and omised . Those women r and omised had received a mean of one year of therapy , mean age was 62.8 years and total follow-up time was 6491 person years . Discussion The WISDOM experience leads to some simple messages . The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery . When a trial is very costly and beyond the re sources of one country , funders and investigators should make every effort to develop international collaboration with joint funding Objective : To evaluate the effects of hormone therapy ( HT ) on cognition and subjective quality of life ( QoL ) in recently postmenopausal women with cognitive complaints . Methods : Cognitive Complaints in Early Menopause Trial ( COGENT ) was a r and omized , double-blind , placebo-controlled , multicenter , pilot study of 180 healthy postmenopausal women aged 45 to 55 years , r and omly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months . Outcome measures included memory , subjective cognition , QoL , sexuality , and sleep , which were assessed at baseline and month 4 . Results : The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women ’s Health Initiative . There were no differences between groups on any cognitive or QoL measures , except for an increase in sexual interest and thoughts with HT . Modest negative effects on short- and long-term verbal memory approached significance ( p < 0.10 ) . Women with baseline vasomotor symptoms ( VMS ) showed a decrease in VMS and an improvement in general QoL , but no cognitive benefit vs placebo . Conclusions : With the power to detect an effect size of ≥0.45 , this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women . GLOSSARY : BTA = Brief Test of Attention ; BVRT = Benton Visual Retention Test ; COGENT = Cognitive Complaints in Early Menopause Trial ; CRT = Educational Testing Service Card Rotation Test ; CVLT = California Verbal Learning ; FAS = Letter Fluency Test ; HERS = Heart and Estrogen/progestin Replacement Study ; HT = hormone therapy ; MFSQ = McCoy Female Sexuality Scale Question naire ; MFQ = The Memory Functioning Question naire ; PANAS = Positive and Negative Affect Scale ; PSQI = The Pittsburgh Sleep Quality Index ; QoL = subjective quality of life ; SWAN = Study of Women ’s Health Across the Nation ; UQoL = Utian Quality of Life ; VMS = vasomotor symptoms Test ; WHI = Women ’s Health Initiative ; WHISCA = WHI Study of Cognitive Aging ; WMS-R/DGT-F , MS-R/DGT-B = Digit Span Forward and Backward Subtests of the Wechsler Memory Scale – Revised Menopause impacts 25 million women world wide each year , and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030 . Menopause has been associated with symptoms of hot flashes , night sweats , dysphoric mood , sleep disturbance , and conditions of cardiovascular disease , depression , osteoporosis , osteoarthritis , depression , dementia , and frailty . Conventional hormone replacement therapy results in increased thrombotic events , and an increased risk of breast cancer and dementia as evidence d in large prospect i ve clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women 's Health Initiative . A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors . Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile , yet long-term studies of this treatment model are lacking . The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol , estradiol , progesterone , DHEA , and testosterone on cardiovascular biomarkers , hemostatic , inflammatory , immune signaling factors ; quality -of-life measures ; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care . A prospect i ve , cohort , closed-label study received approval from the Human Subjects Committee . Recruitment from outpatient clinics at an academic medical center and the community at large result ed in three hundred women giving signed consent . Seventy-five women who met strict inclusion /exclusion criteria were enrolled .  Baseline hormone evaluation was performed along with baseline experimental measures . Following this , women received compounded transdermal bioidentical hormone therapy of BiEst ( 80%Estriol/20%Estradiol ) , and /or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women . The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic , ischemic , or neuronal injury . Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of and rogens of DHEA and Testosterone if indicated . Experimental subjects were monitored for 36 months . Baseline , 2-month , and annual values were obtained for : blood pressure , body mass index , fasting glucose , Homeostasis Metabolic Assessment of Insulin Resistance ( HOMA-IR ) , fasting triglycerides , total Factor VII , Factor VIII , fibrinogen , Antithrombin III , Plasminogen Activator Inhibitor1(PAL-1 ) , C-reactive protein ( CRP ) , Interleukin-6 ( IL-6 ) , Matrix Metalloproteinase-9 ( MMP-9 ) , Tumor Necrosis Factor-alpha ( TNF ) , Insulin-like Growth Factor ( IGF-1 ) , and sex steroid levels . Psychosocial measures included : Greene Climacteric Scale , Visual Analog Pain Scale , Hamilton Anxiety Scale , Hamilton Depression Scale , Holmes Rahe Stress Scale , Job Strain , and Home Strain . Health outcome measures included the number of prescribed medications used , number of co-morbidities , and endometrial thickness in postmenopausal women with intact uteri . Subjects receiving  compounded transdermal bioidentical hormone therapy showed significant favorable changes in : Greene Climacteric Scale scores , Hamilton Anxiety Scale , Hamilton Depression Scale , Visual Analog Pain Scale , fasting glucose , fasting triglycerides , MMP-9 , C-reactive Protein , fibrinogen , Factor VII , Factor VIII , Insulin-Like Growth Factor 1 , and health outcomes of co-morbidities and a number of prescribed medications . Antithrombin III levels were significantly decreased at 36 months . All other measures did not exhibit significant effects . Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women . Cardiovascular biomarkers , inflammatory factors , immune signaling factors , and health outcomes were favorably impacted , despite very high life stress , and home and work strain in study subjects . The therapy did not adversely alter the net prothrombotic potential , and there were no associated adverse events . This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in population s with high perceived stress and a history of stressful life events prior to , or during the menopausal transition 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 The National Institutes of Health ( NIH ) has instructed participants in the estrogen-alone study of the Women ’s Health Initiative ( WHI ) , a large multi-center trial , to stop taking their study pills and to begin the follow-up phase of the study . Letters have been sent to all participants in the estrogenalone study , 11,000 healthy postmenopausal women who have had a hysterectomy , informing them of a recent NIH review of the study data . After careful consideration of the data , NIH has concluded that with an average of nearly 7 years of follow-up completed , estrogen alone does not appear to affect ( either increase or decrease ) heart disease , a key question of the study . At the same time , estrogen alone appears to increase the risk of stroke and decrease the risk of hip fracture . It has not increased the risk of breast cancer during the time period of the study . The increased risk of stroke in the estrogen-alone study is similar to what was found in the WHI study of estrogen plus progestin when that trial was stopped in July 2002 . In that study , women taking estrogen plus progestin had 8 more strokes per year for every 10,000 women than those taking the placebo . The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study . This is especially true if estrogen alone does not affect ( either increase or decrease ) heart disease , as appears to be the case in the current study . The NIH has determined that the results would not likely change if the estrogen trial continued to its planned completion in 2005 . Furthermore , enough data have been obtained to assess the overall risks and benefits of the use of estrogen in this trial . WHI research ers have begun a detailed analysis of the data from the estrogen-alone study and expect to report full results in the next two months . The report , to be published in a peer- review ed journal , will include additional data collected through the end of February 2004 . A separate report will contain information on  probable dementia or mild cognitive impairment in the women age 65 and older who participated in the estrogen-alone WHI-Memory Study ( WHIMS ) , an ancillary study of the WHI Hormone Trials . Preliminary data suggest that for the WHIMS participants who were on estrogen  alone when compared to the women who were taking the placebo , there was a trend toward increased risk of probable dementia and /or mild cognitive impairment . The WHI estrogen study was design ed to assess the effect of long-term use of hormone therapy in healthy postmenopausal women on the prevention of heart disease and hip fractures , and any associated change in risk for breast cancer . It was not design ed to evaluate the short-term risks and benefits of hormones for the treatment of moderate to severe menopausal symptoms . The estrogen-alone study involved women ages 50 to 79 years . Study participants were r and omly assigned to a daily dose of estrogen—0.625 mg/day of conjugated equine estrogen — or a placebo . The NIH decision to stop the estrogen-alone trial was made on February 2 , 2004 . In November and December 2003 , the WHI Data and Safety Monitoring Board ( DSMB ) , an independent advisory committee which regularly review s study data and oversees the safety of study participants , review ed the latest data from the estrogen-alone study . The DSMB was split as to whether the study pills should be stopped or whether the pills should be continued , provided that a letter would be sent to the participants clearly informing them of the stroke risks and other findings . After careful review , the NIH decided that women in the estrogen-alone study should stop taking their study pills . From the National Heart , Lung , and Blood Institute of the National Institutes of Health 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 OBJECTIVE To eluci date the effects of low-dose 17beta-estradiol and norethisterone ( hormone therapy [ HT ] ) versus placebo in women with Alzheimer Disease ( AD ) on cognition , depressive symptoms , and activities of daily living . DESIGN A 12-month r and omized , double-blind , placebo-controlled study , stratified by apolipoprotein E ( ApoE ) genotype ( with versus without the epsilon4 allele ) , duration of education ( < or = 9 versus > 9 years ) , and age ( < or = 75 versus > 75 years ) performed during 2000 - 2004 . SETTING Ambulatory memory clinic in a general hospital . PARTICIPANTS Sixty-five female out patients aged 65 - 89 years who met criteria for probable AD according to Diagnostic and Statistical Manual of Mental Disorders , fourth edition and International Classification of Diseases , tenth edition . Ten patients were excluded , result ing in 55 participants who had at least one posttreatment efficacy evaluation . INTERVENTION R and omly assigned to receive either 1-mg estradiol and 0.5-mg norethisterone or placebo once daily . MEASUREMENTS Cognitive variables were the Dementia Rating Scale , tests from Consortium to Establish a Registry for AD , Global Deterioration Scale ( GDS ) and Barthel Index . RESULTS When only treatment effects were compared by analysis of variance , there were nonsignificant differences between treatment groups for all efficacy variables . A linear model analysis , including stratifying factors in addition to treatment in the model , revealed a significant main effect on mood . The depressive symptoms were lower in the HT group than in the placebo group . Those treated with HT without the ApoE epsilon4 allele had better mood , Word Learning Memory score , and GDS score . Those in the HT group with a higher level of education obtained a better GDS score . Adverse events did not differ between the groups . CONCLUSION HT interacts with ApoE genotype in women with AD . Women without an ApoE epsilon4 allele may get better mood and cognition with HT . HT may reduce depressive mood and give less cognitive decline AIMS The use of hormone therapy ( HT ) is a relevant and topical issue in the treatment of menopausal symptoms in women . Information regarding the effects of combination treatment with estrogen and progesterone as well as treatment timing on cognitive function is lacking and was evaluated in healthy pre- and postmenopausal women . METHODS Sixteen premenopausal ( 45 - 51 years ) and 16 postmenopausal ( 58 - 70 years ) women were r and omly assigned to receive either estrogen + progestin therapy ( HT ) or placebo ( PL ) for six months . The study was double-blind . Cognitive performance was measured at baseline and follow up with tests of verbal and visuomotor functions , verbal and visual memory , and attention . RESULTS In premenopausal women , cognitive attention , when compared to baseline , improved with HT but declined slightly with PL in the two-choice reaction time task ( P = 0.049 ) , while PL was associated with better performance in tests of shared attention ( P = 0.024 ) and auditory attention ( P < 0.05 ) . In postmenopausal women , HT was associated with improved performance in verbal episodic memory ( P = 0.024 ) and a minor decline in auditory attention ( P = 0.025 ) . CONCLUSIONS HT , with estradiol valerate and norethisterone , in healthy women showed only minor effects on attention around the menopausal transition and on memory in postmenopause 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 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
Women taking HT had a significantly decreased incidence of fracture with long-term use .
Research ers found no strong evidence that HT has a clinical ly meaningful impact on the incidence of colorectal cancer .
AUTHORS ' CONCLUSIONS : Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT , provided they do not have specific contraindications .
HT may be unsuitable for some women , including those at increased risk of cardiovascular disease , increased risk of thromboembolic disease ( such as those with obesity or a history of venous thrombosis ) or increased risk of some types of cancer ( such as breast cancer , in women with a uterus ) .
The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented .
HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia , nor for prevention of deterioration of cognitive function in postmenopausal women .
Although HT is considered effective for the prevention of postmenopausal osteoporosis , it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable .
BACKGROUND : Hormone therapy ( HT ) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease , osteoporosis and  dementia in older women .
This is an up date d version of a Cochrane review first published in 2005 .
OBJECTIVES : To assess effects of long-term HT ( at least 1 year 's duration ) on mortality , cardiovascular outcomes , cancer , gallbladder disease , fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment .