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 Hormone therapy in menopausal women with cognitive complaints Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease. 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 Reproductive hormone exposure timing and ischemic heart disease: Complicated answers to a simple question. Health-related quality of life during hormone therapy after breast cancer: a randomized trial Hormone therapy and Alzheimer disease dementia Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study The effect of tibolone and continuous combined conjugated equine oestrogens plus medroxyprogesterone acetate on progression of carotid intima-media thickness: the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study. Long-Term Prevention with Hormone-Replacement Therapy after the Menopause: Which Women should be Targeted? NIH asks participants in Women's Health Initiative estrogen-alone study to stop study pills, begin follow-up phase. Efficacy and safety of DT56a compared to hormone therapy in Greek post-menopausal 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 Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy 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. 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. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. Healthy women with a family history of breast cancer: impact of a tailored genetic counseling intervention on risk perception, knowledge, and menopausal therapy decision making. A Prospective, Observational Study of Postmenopausal Hormone Therapy and Primary Prevention of Cardiovascular Disease Some problems with Cochrane reviews of diet and chronic disease Derivation and validation of updated QFracture algorithm to predict risk of osteoporotic fracture in primary care in the United Kingdom: prospective open cohort study 17β-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. Psychosocial interventions for people with dementia: An overview and commentary on recent developments A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule (和颜坤泰胶囊) and Hormone Therapy in Perimenopausal Women Evidence-based review of therapies at the menopause. Osteoporosis in menopause. Osteoporosis medication and reduced mortality risk in elderly women and men. Postmenopausal hormone therapy and cognitive outcomes: The Women's Health Initiative Memory Study (WHIMS) The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The rationale, design, and baseline characteristics of the Women's Health Initiative Memory Study of Younger Women (WHIMS-Y)
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 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 Description This guideline up date s the 2008 American College of Physicians ( ACP ) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women . This guideline is endorsed by the American Academy of Family Physicians . Methods The ACP Clinical Guidelines Committee based these recommendations on a systematic review of r and omized controlled trials ; systematic review s ; large observational studies ( for adverse events ) ; and case reports ( for rare events ) that were published between 2 January 2005 and 3 June 2011 . The review was up date d to July 2016 by using a machine-learning method , and a limited up date to October 2016 was done . Clinical outcomes evaluated were fractures and adverse events . This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density , including pharmaceutical prescriptions , calcium , vitamin D , and estrogen . Evidence was grade d according to the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . Target Audience and Patient Population The target audience for this guideline includes all clinicians . The target patient population includes men and women with low bone density and osteoporosis . Recommendation 1 ACP recommends that clinicians offer pharmacologic treatment with alendronate , risedronate , zoledronic acid , or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis . ( Grade : strong recommendation ; high- quality evidence ) . Recommendation 2 ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 3 ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinical ly recognized osteoporosis . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 4 ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 5 ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women . ( Grade : strong recommendation ; moderate- quality evidence ) . Recommendation 6 ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences , fracture risk profile , and benefits , harms , and costs of medications . ( Grade : weak recommendation ; low- quality evidence ) 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 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 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 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 Aim To study the effects of menopausal hormone therapy ( HT ) on health-related quality of life in women after breast cancer . Patients and methods In the Stockholm trial , breast cancer survivors were r and omized to HT ( estradiol and progestogen ) or to a control group ( no treatment ) .  A subgroup of 75 women was studied ( 38 with HT , 37 controls ) . Fifty patients were on concomitant tamoxifen .  Patients completed three question naires ( EORTC QLQ C-30 , EORTC QLQ-BR 23 and the Hospital Anxiety and Depression Scale ( HADS ) ) during 1 year of treatment . Results A significant group-by-time interaction was found for improvement of insomnia in the HT group ( p < 0.001 ) . Within the HT group , but not in the control group , there was significant improvement for HADS anxiety , HADS depression , emotional , cognitive , and social functions and global quality of life . When HT was added to tamoxifen , the increase in global quality of life was significant ( p < 0.01 ) . Conclusion The effects of HT on quality of life in breast cancer survivors have not previously been reported . The present data suggest that this controversial treatment may improve quality of life after breast cancer 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 Summary Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture ( caused by minimal trauma ) were receiving the recommended osteoporosis therapy . We found that approximately half of these women were not being treated , indicating a significant care gap in osteoporosis treatment . Introduction Prevalent fragility fracture strongly predicts future fracture . Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment . We aim ed to describe post fracture care in Canadian women using a large , population -based prospect i ve cohort that began in 1995–1997 . Methods We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study . Information on medication use and incident clinical fragility fractures was obtained during a yearly question naire or interview and fractures were confirmed by radiographic/medical reports . Results Over the 10-year study period , 42–56 % of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication . During year 1 of the study , 22 % of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26 % were on hormone therapy ( HT ) . We were not able to differentiate HT use for menopause symptoms vs osteoporosis . Use of bisphosphonate therapy  increased over time ; odds ratio ( OR ) for use at year 10 compared to use at year 1 was 3.65 ( 95 % confidence interval ( CI ) 1.83–7.26 ) . In contrast , HT use declined , with an OR of 0.07 ( 95%CI 0.02–0.24 ) at year 10 compared to year 1 of the study . Conclusion In a large population -based cohort study , we found a therapeutic care gap in women with osteoporosis and fragility fractures . Although bisphosphonate therapy usage improved over time , a substantial gap remains AIMS At the time of the design of the Osteoporosis Prevention and Arterial effects of tiboLone ( OPAL ) study in 1996 , oral hormone therapy ( HT ) was assumed to reduce cardiovascular risk . The evidence mainly came from the effects of combined conjugated equine oestrogens plus medroxyprogesterone acetate ( CEE/MPA ) therapy . Other HT regimes had not been studied widely . Tibolone , a selective tissue oestrogenic activity regulator , has several effects on cardiovascular risk factors , one of which is HDL lowering . Because the overall effect of tibolone on cardiovascular risk was unknown , the OPAL study was design ed . METHODS AND RESULTS The OPAL study was a three-arm , r and omized , placebo-controlled , double-blind study to determine the effect of tibolone ( 2.5 mg daily ) and of CEE/MPA ( 0.625/2.5 mg daily ) over 3 years on progression of carotid intima-media thickness ( CIMT ) in 866 healthy post-menopausal women . The women were recruited from six US and five European centres . The primary outcome was change in mean common CIMT . Annual common CIMT progression rates in the tibolone and CEE/MPA groups were higher than in the placebo group : 0.0077 mm [ 95 % confidence interval ( CI ) 0.0051 - 0.0103 ] in the tibolone group , 0.0074 mm ( 0.0048 - 0.0099 ) in the CEE/MPA group , and 0.0035 mm ( 0.009 - 0.0061 ) in the placebo group . The differences with placebo ( 0.0042 mm/year for tibolone and 0.0039 mm/year for CEE/MPA ) were statistically significant . HDL cholesterol increased in CEE/MPA group and was lowered in the tibolone group . CONCLUSION Both tibolone and CEE/MPA showed increased progression of common CIMT . Translation of the increased common CIMT progression of the CEE/MPA group into cardiovascular disease risk could not fully explain the observed increased cardiovascular risk as observed in the Women 's Health Initiative study . This suggests that the net effect of tibolone and CEE/MPA on cardiovascular events may depend on the combined effects on the arterial wall , clotting factors , and possibly inflammation 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 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 Background : Hormone therapy ( HT ) is the treatment of choice for the alleviation of menopausal symptoms ; concerns , however , about its concomitant long-term health risks have limited its use . DT56a is a unique enzymatic isolate of soybeans . The purpose of our study was to evaluate the efficacy and safety of DT56a , compared to HT , in symptomatic post-menopausal women . Subjects and methods : Eighty-nine post-menopausal women were studied prospect ively . Women with climacteric symptoms were r and omly assigned to receive eitherDT56a ( no.=27 ) or oral low dose continuous combined HT ( no.=26 ) . Symptomatic women not wishing to receive any treatment served as controls ( no.=36 ) . Menopausal symptoms as assessed through the Kupperman index , serum lipids and lipoproteins , calcium , as well as bone mineral density ( BMD ) , endometrial thickness , and mammography were assessed at baseline and at 12 months . Results : Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms ( mean difference in Kupperman score , DT56a group : −3.98 , HT group −5.601 , no treatment group + 1.76 , p-value < 0.001 ) . Lumbar spine BMD T-score was significantly lower in women receiving no treatment , as opposed to the two treatment arms which showed no significant change ( No treatment , baseline : −0.60 , final : −0.85 , p=0.001 ; HT , baseline : −84 , final −0.99 , p=0.79 ; DT56a , baseline −0.51 , final : −0.76 , p=0.75 ) . No differences in femoral bone density , ET or mammography classification were detected in any of the treatment arms . Likewise , serum lipids or lipoproteins did not differ between the three groups . Conclusions : DT56a decreased menopausal symptoms significantly and in the same degree as HT 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 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 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 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 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 BACKGROUND Women with a family history of breast cancer have several menopausal therapy options , including tamoxifen , hormone therapy ( HT ) , alternative medications , or no treatment . This complex decision should be based on each woman 's risk to develop breast cancer , menopausal symptoms , preferences , and risks for other conditions . The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge , risk perception , and decision making in a group of healthy women who had a first-degree relative with breast cancer . METHODS Forty-eight cancer-free menopausal women age > or = 40 years who had at least one first-degree relative with breast cancer were r and omized to a genetic counseling intervention or control .  Intervention participants were given a personalized risk assessment for breast cancer , heart disease , osteoporosis , and uterine cancer based on family history and personal health data . Knowledge , risk perception , and medication usage were measured at baseline , 1 month , and 6 months . RESULTS Knowledge was higher in the intervention group at both follow-up time points postintervention . Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline , as was perceived risk of developing heart disease . Although the counseling intervention did affect both knowledge and risk perception , overall , both groups were reluctant to take any form of menopausal therapy . CONCLUSIONS A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception ; however , it is unclear that the intervention influenced menopausal treatment decisions 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 The sum of evidence -based nutrition has to be more than a Cochrane-type meta- analysis of r and omised controlled trials ( RCTs ) . Most of the evidence base in nutrition is observational , especially cohort studies . RCTs of diet change through to disease outcome are uncommon and the change has usually been addition or removal of only a single food component . Trials with whole diets through to disease outcome are rare and dietary changes made by individuals are unlikely to be an exact copy of the prescription . It is hard to even imagine a trial in which half ( r and omised ) of a large group of middle-aged people agree to avoid vegetables for 5 y and be followed up to see who will develop cancer . Most of the USA 's health cl aims , permitted by the Food and Drug Administration , are not supported by RCTs . But where controlled trials of nutritional change and disease outcome have been achieved , they must be review ed very carefully . Two Cochrane review s on diet and cardiovascular disease ( CVD ) , published in the widely read British Medical Journal ( BMJ ) , were criticised after their publication and the conclusions have not been subsequently adopted by expert committees . The first of these review s was ‘ Dietary fat and prevention of CVD : a systematic review ’ . The second was ‘ Systematic review of long term effects of advice to reduce dietary salt in adults ’ . A critique of these two Cochrane review s is presented here as a contribution to our discussion of the potential of Cochrane methodology to the reliability of knowledge about diet and disease Objective To develop and vali date an up date d version of the QFracture algorithm for estimating the risk of a patient sustaining an osteoporotic fracture or hip fracture in a primary care population . Design Prospect i ve open cohort study using routinely collected data from 420 general practice s in the United Kingdom to develop up date d QFracture scores and 207 practice s to vali date scores . Cox ’s proportional hazards model was used in the derivation cohort to derive risk equations using several explanatory variables . We calculated measures of calibration and discrimination using the validation cohort . Participants 3 142 673 patients in derivation cohort and 1 583 373 in validation cohort , aged 30 - 100 years , who contributed 23 608 337 and 11 732 106 person years of observation , respectively . We identified 59 772 incident diagnoses of osteoporotic fracture in the derivation cohort and 28 685 in the validation cohort . Outcomes Incident diagnosis of osteoporotic fracture ( vertebral , distal radius , proximal humerus , or hip ) and incident hip fracture recorded in general practice records or linked cause of death records . Results We found significant independent associations with overall fracture risk in women for age , body mass index , ethnic origin , alcohol intake , smoking status , chronic obstructive pulmonary disease or asthma , any cancer , cardiovascular disease , dementia , diagnosis or treatment for epilepsy , history of falls , chronic liver disease , Parkinson ’s disease , rheumatoid arthritis or systemic lupus erythematosus , chronic renal disease , type 1 diabetes , type 2 diabetes , previous fracture , endocrine disorders , gastrointestinal malabsorption , any antidepressants , corticosteroids , unopposed hormone replacement therapy , and parental history of osteoporosis . Risk factors for hip fracture in women were similar except for gastrointestinal malabsorption and parental history of hip fracture . Risk factors for men were largely the same as those for women but also included care home residence . The up date d hip fracture algorithm explained 71.7 % ( 95 % confidence interval 71.1 % to 72.3 % ) of the variation in women and 70.4 % ( 69.3 % to 71.5 % ) in men . D statistic values for hip fracture were high for women ( 3.26 , 3.21 to 3.31 ) and men ( 3.15 , 3.06 to 3.24 ) , and higher than for osteoporotic fracture . Values for the area under the receiver operating characteristics curves for hip fracture were 0.89 for women and 0.88 for men , compared with 0.79 and 0.71 for osteoporotic fracture , respectively . The up date d algorithms performed better than the 2009 algorithms . Conclusions Two QFracture algorithms were up date d to predict risk of osteoporotic and hip fracture in primary care population s to include ethnic origin , all classes of antidepressants , chronic obstructive pulmonary disease , epilepsy , dementia , Parkinson ’s disease , cancer , systemic lupus erythematosus , chronic renal disease , type 1 diabetes , previous fragility fracture , and care home residence . These up date d algorithms showed improved performance compared with previous QFracture algorithms reported in 2009 Several formulations combining estrogens and progestins for hormone therapy ( HT ) have been approved worldwide for the treatment of menopausal symptoms , yet recent data indicate a decline in their use and an increase in compounded bioidentical HT . Up to now , no single product combining natural 17β-estradiol and progesterone has been approved by the US Food and Drug Administration ( FDA ) or the European Medicines Agency ( EMA ) . A phase 3 trial ( REPLENISH ) is underway to study a novel oral formulation of solubilized 17β-estradiol and natural progesterone combined in a single gelatin capsule ( TX-001HR ; TherapeuticsMD , Inc , Boca Raton , FL ) for treating vasomotor symptoms ( VMS ) in postmenopausal women . The REPLENISH trial evaluates the efficacy and safety of TX-001HR ( 4 doses ) versus placebo for the reduction of moderate to severe VMS frequency and severity at 4 and 12 weeks and evaluates the endometrial safety of the combinations at 1 year . TX-001HR contains hormones that are molecularly identical to endogenous estradiol and progesterone and is intended as an option for women who prefer bioidentical hormones ; further , it does not contain peanut oil , a common allergen . The constituents of TX-001HR , in a pharmacokinetic report , showed similar bioavailability and safety compared with reference estradiol tablets and micronized progesterone capsules administered together . Published data suggest a safer profile of estradiol and natural progesterone compared with HT containing conjugated equine estrogens and progestins . This report summarizes the methodology of the REPLENISH trial and review s the evidence suggesting clinical differences between HT containing progesterone or progestins , and estradiol or conjugated equine estrogens An influential review in 2010 concluded that non-pharmacological multi-component interventions have positive effects on cognitive functioning , activities of daily living , behaviour and mood of people with dementia . Our aim here is to provide an up-to- date overview of research into psychosocial interventions and their impact on psychosocial outcomes . We focused on r and omised controlled trials , controlled studies and review s published between October 2008 and August 2015 , since the earlier review . The search of PsychInfo , Medline and the Cochrane data base of systematic review s yielded 61 relevant articles , organised into four themes echoing key phases of the care pathway : Living at home with dementia ( five review s , eight studies ) , carer interventions ( three review s , four studies ) , interventions in residential care ( 16 review s , 12 studies ) and end-of-life care ( three review s , two studies ) , along with an additional group spanning community and institutional setting s ( six review s , two studies ) . Community findings suggested that appointment of dementia specialists and attention to case management can produce positive outcomes ;  physical therapies , cognitive training and modified cognitive behaviour therapy also had a range of benefits . There was more limited evidence of positive benefits for people with dementia through interventions with family carers . Thirty-two articles focused on the management of ‘ behavioural symptoms ’ through a range of interventions all of which had some evidence of benefit . Also a range of multi-component and specific interventions had benefits for cognitive , emotional and behavioural well-being of people with dementia in residential setting s , as well as for quality of life . Overall , interventions tended to be short term with impact only measured in the short term . We recommend further research on interventions to promote living well in the community post-diagnosis and to address end-of-life care . Development of psychosocial interventions would benefit from moving beyond the focus on control of behaviours to focus on wider aspects of life for people with dementia Objective To evaluate the efficacy and safety of Heyan Kuntai Capsule ( 和颜坤泰胶囊 , HYKT ) and hormone therapy ( HT ) on perimenopausal syndromes ( PMSs ) . Methods From 2005 to 2008 , 390 women with PMSs were recruited from 4 clinic centers . The inclusion criteria included ages 40 to 60 years , estradiol ( E2 ) below 30 ng/L , and follicle stimulating hormone ( FSH ) above 40 IU/L , etc . The patients were r and omly assigned to HYKT group or HT group by r and om number table method , administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months . During treatment , the patients were interviewed quarterly , Kupperman Menopausal Index ( KMI ) scores , hot flush scores , insomnia scores , Menopause-Specific Quality of Life ( MENQOL ) scores and adverse effects were used for evaluating drug efficacy and safety respectively . The last interview was made at the end of 12-month treatment Results After treatment , KMI scores of HYKT group and HT group were both significantly decreased compared with baseline ( P < 0.01 ) and there was no significant difference between groups ( P > 0.05 ) , except that KMI of HYKT group was higher after 3-month treatment ( P < 0.05 ) . After treatment , hot flush and insomnia scores were both improved significantly in two groups ( P < 0.01 ) ; and HT had a better performance than HYKT in improving hot flush ( P < 0.05 ) . MENQOL were significantly improved in both groups after treatment ( P < 0.01 ) ; but there was no significant difference between two groups ( P > 0.05 ) . The incidence of adverse event in the HYKT group was much lower than that in the HT group ( P < 0.01 ) . Conclusions HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions . Although HYKT exerted curative effects more slowly than hormone , it possessed better safety profile than hormone Background and Objective The highest level of scientific evidence available for each therapy for menopausal symptoms was sought , for example , systematic review s of r and omised controlled trials ( RCTs ) . Results There is reasonable evidence that some symptoms are modified by lifestyle , for example , cessation of smoking , exercise , reduction of alcohol , diet and alleviation of psychosocial stress . No complementary medicine , for example , phytoestrogens , black cohosh , herbal or homeopathic medicines or complementary therapies , for example , acupuncture , yoga , chiropractic manipulation , reflexology or magnetic devices have a greater effect than the usual placebo effect seen in quality blinded RCTs . Some have potential side-effects . So-called ' bioidentical hormones ' have no evidence -base and potential for harm . None of the above therapies have evidence of efficacy and long-term safety . Selective serotonin and noradrenaline re-uptake inhibitors ameliorate vasomotor symptoms and sometimes menopausal depression better than placebo . The most effective therapy for menopausal ( oestrogen ) deficiency symptoms is oestrogen which is the main component of hormone replacement therapies ( HRT ) . Compared with placebo HRT is highly effective in relieving hot flushes , night sweats , dry vagina and dyspareunia . It also improved joint pains , sexuality and sleeplessness and reduced subsequent fractures in RCTs . The increased risk of oral HRT for thromboembolism is small around menopause , for those without thrombotic risk factors , and is not elevated with non-oral routes . Cardiovascular disease may be reduced when HRT is initiated near menopause . Breast cancer risk increases after several years with the use of oral HRT containing progestogens at an annual rate of 8/10 000 ( < 0.1 % ) . No increase in breast cancer risk was seen with oestrogen-only HRT OBJECTIVE To provide guidelines for the health care provider on the prevention , diagnosis , and clinical management of postmenopausal osteoporosis . OUTCOMES Strategies for identifying and evaluating high-risk individuals , the use of bone mineral density ( BMD ) and bone turnover markers in assessing diagnosis and response to management , and recommendations regarding nutrition , physical activity , and the selection of pharmacologic therapy to prevent and manage osteoporosis . EVIDENCE Published literature was retrieved through search es of PubMed and The Cochrane Library on August 30 and September 18 , 2012 , respectively . The strategy included the use of appropriate controlled vocabulary ( e.g. , oteoporosis , bone density , menopause ) and key words ( e.g. , bone health , bone loss , BMD ) . Results were restricted to systematic review s , practice guidelines , r and omized and controlled clinical trials , and observational studies published in English or French . The search was limited to the publication years 2009 and following , and up date s were incorporated into the guideline to March 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology assessment -related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies CONTEXT Osteoporotic fractures are associated with premature mortality .  Antiresorptive treatment reduces refracture but mortality reduction is unclear . OBJECTIVE The objective of the study was to examine the effect of osteoporosis treatment [ bisphosphonates ( BP ) , hormone therapy ( HT ) , and calcium ± vitamin D only ( CaD ) ] on mortality risk . DESIGN This was a prospect i ve cohort study ( April 1989 to May 2007 ) . SETTING The study was conducted with community-dwelling elderly ( aged 60 + yr ) subjects in Dubbo , a semiurban city , Australia . SUBJECTS Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study . MAIN OUTCOME MEASURE Mortality according to treatment group was recorded . RESULTS There were 325 ( BP , n = 106 ; HT , n = 77 ; CaD , n = 142 ) women and 37 men ( BP , n = 15 ; CaD , n = 22 ) on treatment . In women , mortality rates were lower with BP 0.8/100 person-years ( 0.4 , 1.4 ) and HT 1.2/100 person-years ( 0.7 , 2.1 ) but not CaD 3.2/100 person-years ( 2.5 , 4.1 ) vs. no treatment 3.5/100 person-years ( 3.1 , 3.8 ) . Accounting for age , fracture occurrence , comorbidities , quadriceps strength , and bone mineral density , mortality risk remained lower for women on BP [ hazard ratio ( HR ) 0.3 ( 0.2 , 0.6 ) ] but not HT [ HR 0.8 ( 0.4 , 1.8 ) ] . For 429 women with fractures , mortality risk was still reduced in the BP group [ adjusted HR 0.3 ( 0.2 , 0.7 ) ] , not accounted for by a reduction in subsequent fractures . In men , lower mortality rates were observed with BP but not CaD [ BP 1.0/100 person-years ( 0.3 , 3.9 ) and CaD 3.1/100 person-years ( 1.5 , 6.6 ) vs. no treatment 4.3/100 person-years ( 3.9 , 4.8 ) ] . After adjustment , mortality was similar , although not significant [ HR 0.5 ( 0.1 , 2.0 ) ] . CONCLUSIONS Osteoporosis therapy appears to reduce mortality risk in women and possibly men This review discusses major findings from the Women 's Health Initiative Memory Study ( WHIMS ) . WHIMS reported hormone therapy (HT)--conjugated equine estrogen ( CEE ) with or without medroxyprogesterone acetate (MPA)--increased the risk for dementia ( HR 1.76 [ 95 % CI , 1.19 - 2.60 ] ; P=0.005 ) and global cognitive decline , with a mean decrement relative to placebo of 0.21 points on the Modified Mini Mental State Examination ( 3MS ) ( P=0.006 ) in women age 65 and older . A subset of WHIMS participants joined the ancillary WHI Study of Cognitive Aging ( WHISCA ) trials , in which domain-specific cognitive tests and mood were measured annually . Compared with placebo , CEE+MPA had a negative impact on verbal memory over time ( P=0.01 ) ; and CEE-Alone was associated with lower spatial rotational ability ( P < or = 0.01 ) at the initial assessment , but the difference diminished over time . The ancillary WHIMS-MRI study measured sub clinical cerebrovascular disease to possibly explain the negative cognitive findings reported by WHIMS and the increased clinical stroke in older women reported by the WHI . WHIMS-MRI reported that while CEE+MPA and CEE-Alone were not associated with increased ischemic brain lesion volume relative to placebo ; both CEE+MPA and CEE-Alone were associated with lower mean brain volumes in the hippocampus ( P=0.05 ) ; frontal lobe ( P=0.004 ) ; and total brain ( P=0.07 ) . HT-associated reductions in hippocampal volumes were greatest in women with baseline 3MS scores < or = 90 OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually 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
In relatively healthy women , combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event ( after one year 's use ) , stroke ( after three years ) , breast cancer and gallbladder disease .
Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism , stroke and gallbladder disease ( after one to two years , three years and seven years ' use respectively ) , but did not significantly increase the risk of breast cancer .
The only statistically significant benefits of HT were a decreased incidence of fractures and ( for combined HT ) colon cancer , with long-term use .
Among women aged over 65 who were relatively healthy ( i.e. generally fit , without overt disease ) and taking continuous combined HT , there was a statistically significant increase in the incidence of dementia .
Among women with cardiovascular disease , long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism .
AUTHORS ' CONCLUSIONS HT is not indicated for the routine management of chronic disease .
We need more evidence on the safety of HT for menopausal symptom control , though short-term use appears to be relatively safe for healthy younger women
BACKGROUND Hormone therapy ( HT ) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease , osteoporosis and dementia in older women .
This is an up date d version of the original Cochrane review first published in 2005 .
OBJECTIVES To assess the effect of long-term HT on mortality , cardiovascular outcomes , cancer , gallbladder disease , cognition , fractures and quality of life .