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Introduction: Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved., Aims: To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines., Materials and Methods: Literature review and consensus of expert opinion., Results and Conclusion: The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Bone mass loss associated with pregnancy and lactation is usually regained in the postpartum period. However, it is not known whether the bone loss is completely recovered in women with a shortened interpregnancy interval (IPI). The aim of this study was to analyze the effect of IPI and gynecological history on postmenopausal osteoporosis., Study Design: The study was conducted among 537 postmenopausal women who were divided into two groups in accordance with the osteoporosis status. Prior to bone densitometry, the patients were questioned about reproductive history. Dual-energy X-ray absorptiometry was used to measure lumbar spinal, femur neck and total femoral bone mineral density., Main Outcome Measure: Association between IPI and postmenopausal osteoporosis was analyzed., Results: The comparison of both groups according to the total duration of breastfeeding did not reveal a considerable variation (p=0.288). In the osteoporosis group the age and duration of menopause were found to be significantly higher (p<0.001) whereas the age of first pregnancy and IPI were notably lower in comparison to the controls group (p<0.001). Multivariate logistic regression analyses revealed that women who have 0-12 months interpregnancy interval have the highest risk for osteoporosis (OR: 4.306; 95% CI, 1.684-11.01). This analysis confirmed that the occurrence of first pregnancy under 27 years of age conveyed a higher risk for osteoporosis, as well., Conclusions: Shortened IPI may have a detrimental effect on bone mineral density in postmenopausal age., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

SERMs represent a diverse group of molecules with varying levels of estrogenic agonist and antagonist activity in target tissues. SERMs have a long regulatory approval history and have been studied for a variety of therapeutic indications. The clinical effects of SERMs have been evaluated in a large number of phase 3 clinical trials. Many of the available SERMs have proved to be effective as chemo-preventive agents and treatments for breast cancer and a number are useful for the prevention and treatment of osteoporosis. The endometrial effect of SERMs has been a key differentiator in clinical practice and a major hurdle for regulatory approval. The effect of SERMs in the vagina also represents a major distinction among different SERMs. This review summarized key clinical finding of SERMs in different target tissues., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Physical activity has been identified as a protective factor against a wide spectrum of diseases, but little is known about the link between older women's health and their professional involvement in sport in the past. The aim of this narrative review is to characterize and summarize the available data concerning the influence of physical activity on morbidity and mortality in former female athletes. Concerning bone health, it seems that physical activity in the past can be protective against osteoporosis in postmenopausal women, but these data come from observational studies only. Also the cardiovascular system appears to benefit in older women from regular sport in the past. This refers mainly to better heart efficiency, and improved endothelial function and metabolic profile. The incidence of different types of neoplasms, especially breast cancer, is also decreased in former athletes. Professional sport, on the other hand, acts negatively on the pelvic floor and is a risk factor for urinary incontinence. The overall effect on mortality is difficult to assess, because of many parameters, such as the sport's intensity, variety of the sport and exposure to extreme danger in some disciplines. Also, caution should be kept in interpretation of the data because of the shortage of well-designed studies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Vitamin E is known to be the most important antioxidant in the body, protecting against the effects of toxic radicals. The main idea behind the studies on vitamin E and bone metabolism stems from the concept that oxidative stress may interfere with the bone formation activity of osteoblasts which in turn can lead to osteoporosis. This mini-review, summarizes the studies on the effects of vitamin E on bone mineral density, fracture risk, bone formation, and resorption markers in perimenopausal women. Current evidence does not the support daily use of vitamin E for protection against osteoporosis and hip fracture risk in perimenopausal women. However some benefit has been shown in some observational studies. Low vitamin E (>6.2mg/day) intake seems to be associated with an OR of 3.0 of hip fracture in current smokers. Compared with the highest quintile of alpha-tocopherol intake, the lowest quintile of intake conferred a multivariable-adjusted HR of 1.86 for hip fracture and 1.20 for any fracture. Alpha-tocopherol supplementation may alter the alpha-tocopherol/gamma-tocopherol ratio; which in turn may be associated with decreased osteoblastic activity. Interventional studies, especially randomized controlled trials (RCT), evaluating a possible causal relationship between serum vitamin E levels and BMD and hip fracture risk in perimenopausal women are needed., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Describe the effects of conjugated estrogens/bazedoxifene (CE/BZA), a new treatment for vasomotor symptoms (VMS) and osteoporosis prevention, on menopause-specific quality of life (MSQOL) across different patient population types in phase 3 clinical trials., Design: MSQOL was prospectively evaluated in 4 randomized, double-blind, placebo-controlled studies. The populations studied included healthy, non-hysterectomized postmenopausal women with symptomatic VMS or vulvar-vaginal atrophy (VVA) and general postmenopausal women (eligible regardless of symptoms). Menopause-specific Quality of Life (MENQOL) questionnaire total and domain scores for CE 0.625 mg/BZA 20mg and CE 0.45 mg/BZA 20mg were evaluated and compared with established thresholds for clinically important differences (CID)., Results: Significant improvements compared with placebo were found with both CE/BZA doses in MENQOL vasomotor domain (-0.61 to -2.23 over 3-24 months) and total scores (-0.24 to -0.94) in the general and symptomatic VMS/VVA populations. Significant improvement compared with placebo in sexual domain (-0.11 to -0.72) was observed with the higher dosage for all populations, and with the lower dosage in the VVA (-0.71 at month 3) and general populations (-0.4 at months 12 and 24). Improvements in vasomotor domain exceeded the CID with both doses in symptomatic VMS populations and with the higher dosage in women with symptomatic VVA; for total MENQOL, the CID was exceeded with the higher dose in symptomatic VMS populations., Conclusions: CE/BZA significantly improved overall and vasomotor-related MSQOL across populations of postmenopausal women with varying baseline symptom statuses. Women with greater menopausal symptoms at baseline were more likely to experience clinically meaningful changes., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The bothersome vasomotor and vaginal symptoms and bone loss that accompany the menopausal transition are associated with significant direct costs due to physician visits and medication, as well as indirect costs from reduced health-related quality of life (HRQoL) and work productivity. With life expectancies increasing, the number of postmenopausal women is also increasing, and more women are remaining in the workforce. These factors have led to an increased burden of menopausal symptoms on healthcare systems. Hormone therapy (HT) has been shown to effectively reduce menopausal symptoms and significantly increase quality-adjusted life years in postmenopausal women, particularly in women experiencing severe symptoms. However, many women discontinue use of HT before their symptoms have dissipated due to safety and tolerability concerns. The tissue selective estrogen complex (TSEC) that pairs bazedoxifene (BZA) with conjugated estrogens (CE) has been developed to provide relief of menopausal symptoms and prevent bone loss without stimulating the breast or endometrium, and to have improved tolerability compared with HT. In this context, BZA 20mg/CE 0.45 and 0.625 mg were shown to prevent bone loss and effectively treat menopausal symptoms in postmenopausal women with an intact uterus, while also demonstrating a favorable safety/tolerability profile. BZA 20mg/CE 0.45 and 0.625 mg were further associated with clinically significant improvements in HRQoL, sleep, and treatment satisfaction. Taken together, the reduction in menopausal symptoms, improvement in HRQoL, and favorable safety/tolerability profile associated with BZA/CE suggest that it is a cost-effective alternative to HT for managing the burden of menopausal symptoms., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Although hormone therapy using estrogens plus progestogens (EPT) is effective for the management of menopausal symptoms (e.g., vasomotor symptoms and vulvar/vaginal atrophy) and prevention/treatment of postmenopausal osteoporosis, EPT is associated with safety and tolerability concerns. A new alternative to EPT is the tissue selective estrogen complex (TSEC), which partners a selective estrogen receptor modulator (SERM) with one or more estrogens and is designed to treat menopausal symptoms and prevent postmenopausal osteoporosis without the tolerability concerns associated with EPT. The first TSEC to reach advanced clinical development is a combination of the SERM bazedoxifene (BZA) with conjugated estrogens (CE). BZA has been shown to inhibit the stimulatory activity of CE on uterine tissue and breast in vitro and in vivo. In clinical studies, BZA/CE treatment has been associated with significant improvements in menopausal symptoms including hot flushes and vulvar/vaginal atrophy and significant increases in bone mineral density, coupled with reductions in bone turnover marker levels and improvements in sleep and health-related quality of life. Additionally, BZA/CE has been shown to have a neutral effect on endometrial and breast tissue because BZA inhibits the stimulatory effects of estrogens in tissue-selective fashion in these 2 organs. Taken together, results of these preclinical and clinical studies indicate that the benefits of estrogens for treating menopausal symptoms are maintained with BZA/CE without endometrial or breast stimulation, resulting in a safe and effective treatment for symptomatic postmenopausal women., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

HRT is known to be effective for the relief of menopausal symptoms and prevention of osteoporosis. HRT should be tailored to the woman, enhancing the beneficial effects of the treatment while minimizing the risks. It is difficult to evaluate data on particular preparations of HRT and the different dosages in isolation. The purpose of this review is to highlight the efficacy and safety specific to oral estradiol and dydrogesterone combinations of four different dose strengths. A systematic literature search using Medline was carried out to identify studies containing efficacy or safety data. The findings of the retrieved publications confirm that estradiol and dydrogesterone combinations give very effective menopausal symptom relief and prevention of osteoporosis whilst maintaining a good safety profile. Data also show that these combinations of HRT give additional benefit to certain metabolic parameters including lipids, insulin, glucose and body fat distribution. By selecting the treatment and dose most suitable for each individual woman at her particular stage of menopause, the benefits can be optimized whilst mitigating the risks. HRT plays an important role in improving and maintaining women's health when used appropriately., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Several selective estrogen receptor modulators are in clinical development for postmenopausal osteoporosis. Bazedoxifene has shown significant reductions in vertebral and non-vertebral (in higher-risk women) fracture risk, with no evidence of breast or endometrial stimulation. Lasofoxifene has demonstrated significant reductions in vertebral and non-vertebral fracture risk, but has been associated with endometrial/uterine effects. Both selective estrogen receptor modulators were generally safe and well tolerated but have been associated with some "class effects" (e.g., hot flushes, venous thromboembolic events). A tissue selective estrogen complex partnering bazedoxifene with conjugated estrogens is under clinical investigation for the treatment of menopausal symptoms and osteoporosis prevention. Future directions in selective estrogen receptor modulator research include ospemifene and RAD 1901., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: The aim of the present study was to investigate the health risks of excess body weight in the light of its protective effects on bone fragility., Methods: Femoral neck and lumbar spine dual X-ray absorptiometry was performed for 1970 Finnish women with a mean baseline age of 58.8 years (range 53.1-65.7 years) in 1994 and 2004. Women were categorized according to baseline BMI into normal <25 kg/m2, overweight 25-29.9 kg/m(2) and obese ≥30 kg/m(2). Weight change (kg) was categorized into tertiles. Co-morbidities, not allowed to be present at baseline, was based on self-reports. Osteoporosis was defined as femoral neck or spinal (L2-L4) T-score <-2.5 SD at 10-year follow-up or <-2.0 SD+low trauma energy follow-up fracture. Uni- and multivariate logistic regression models were used to estimate the 10-year risk of incident health disorders. Adjustment for age, number of diseases, alcohol intake and smoking was used in the multivariate models., Results: Obesity (Ob) and overweight (Ow) were related with higher 10-year risk of hypertension (OR=2.6 (Ob)/OR=1.7 (Ow), p<0.001), coronary artery disease (OR=1.6, p<0.05/OR=1.2, p=NS), diabetes (OR=11.7/OR=5.3, p<0.001), osteoarthritis (OR=1.4, p<0.05/OR=1.1, p=NS), chronic back pain (OR=1.6, p=0.007/OR=1.2, p=NS) and poor self-rated health (OR=2.4, p<0.05/OR=1.5, p=NS) and lower risk of osteoporosis (OR=0.13/OR=0.28, p<0.001). Weight change of less than +1 kg was associated 1.8 and 2.6 times lower 10-year risk of having hypertension and breast cancer than weight change over 6.2 kg. Among obese women the absolute risk increase of hypertension was 17%, of diabetes 12%, and absolute risk reduction of osteoporosis 14% in comparison to BMI <25 kg/m(2)., Conclusions: Health related risks of high BMI outweigh its protective effects on bone. Weight gain increases the risk hypertension and breast cancer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Sex hormones are fundamental for female development and they are important physiologically to maintain the health and normal functioning of several organs such as the brain, heart and bone. It is now clear that the hormonal changes that occur during a woman's life, particularly her estrogen status, can modulate disease activity. This is especially true for cardiovascular and musculo-skeletal diseases, which are two leading causes of morbidity and mortality in women. With the general aging of the population they represent a serious and growing public health concern. Estrogen synthesis and blood levels fluctuate during a woman's life and in this review three broad periods will be considered: reproductive phase, transition and postmenopausal phase. Generally speaking, women in the reproductive phase of their life are at low risk of cardiovascular and musculo-skeletal disorders. However, the onset of menopause and the loss of ovarian function is associated with a significant increase in the prevalence of diseases such as coronary heart disease, osteoarthritis and osteoporosis. The prevalence of these debilitating diseases continues to increase through the postmenopausal period. Estrogen replacement is an obvious treatment approach to counter the problems associated with the loss of ovarian function and subsequent estrogen deficiency. Overall, oral and transdermal estrogen replacement are similarly effective in relieving menopausal symptoms and disorders that manifest during this period of a woman's life. Transdermal estrogen may be preferable in older women because of its lower thrombogenic potential. In this journey through a woman's life current best evidence relating to cardiovascular and musculo-skeletal risk will be reviewed in line with well documented management strategies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Adequate calcium intake is important for optimal bone health. Assessing dietary calcium intake, however, is neither widely done nor standardized in North American clinical practices., Objective: Our goal was to validate a calcium assessment tool (CAT), a modified version of the Calcium Calculator™, against the 3-day food record., Methods: Data were obtained from 348 participants in the ECKO (Evaluation of the Clinical use of vitamin K supplementation in postmenopausal women with Osteopenia) trial. In this study, CAT data was collected at baseline and 3-day food records (FRs) were collected at baseline and 3 months by trained study coordinators. CAT and 3-day FR data were compared using correlations and Bland-Altman plots. Additionally, receiver operator characteristic (ROC) curves of CAT were constructed to identify subjects with low calcium intake at thresholds of 500 mg/day and 1000 mg/day on the 3-day FR curves., Results: Mean calcium intake values per day were 902 mg for the 3-day FRs and 781 mg for the CAT. The Pearson correlation was 0.57 (95% CI: 0.50-0.64). Areas under the ROC curves at thresholds of 500 and 1000 mg calcium were 0.81 (95% CI: 0.73-0.89) and 0.82 (95% CI: 0.78-0.86), respectively., Conclusions: The CAT is a valid tool for the measurement of dietary calcium intake using cut-off values of 500 mg and 1000 mg in postmenopausal women, even though there is only moderate correlation between the CAT and 3-day FR. This tool may facilitate the determination of whether calcium supplements are needed in the clinical setting., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Estrogen deficiency during menopausal transition is associated with rapid bone loss. The purpose of this study was to examine the time of onset, the rate, and predictors of menopausal bone loss., Study Design: Prospective data were analyzed from 160 Chinese women between the ages of 45 to 55 years who participated in the Hong Kong Osteoporotic Study., Main Outcome Measures: All participants were studied yearly for 4 years. Demographic information, menstrual status according to the Stages of Reproductive Aging Workshop (STRAW), and lifestyle habits were recorded as well as bone mineral density (BMD) measured every visit. Baseline follicular stimulating hormone, sex hormone binding globulin, parathyroid hormones, C-terminal telopeptides of type 1 collagen, estradiol and testosterone were also measured., Results: There was no significant bone loss at the spine, femoral neck and total hip in premenopausal women. Maximal bone loss occurred within the STRAW stage -2 and -1. Age at menopause, baseline age, body weight and FSH were independent predictors of bone loss. Subjects in the lowest quartile of baseline body weight (<50 kg) lost bone 2 times faster at spine compared with those in the highest quartile (>61 kg). Subjects in the highest quartile of baseline FSH (>40 IU/l) lost bone 1.3-2.3 times faster at all 3 sites compared with those in the lowest quartile (<5.8 IU/l)., Conclusion: Strategies to retard bone loss should be stressed to middle aged women, especially those with lean body built or with early menopause, to prevent osteoporosis later on in life., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm(2)) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed. The annual mean (SD) change in femoral neck BMD was -0.31% (1.38) in total trochanter -0.35% (1.15) and total hip -0.34% (1.10) and did not differ significantly between measurement sites. Bisphosphonate users had a 2.9%, 1.7% and 1.9% mean adjusted increase in femoral neck, total trochanter and total hip BMD respectively, different from none-users (p<0.05). Subjects with more than three weekly physical activity sessions had less femoral neck bone loss than less active women (p<0.05). The proportion of the variance in BMD changes explained by multivariate models (R(2)) was 12-13%. Women gaining weight had less loss of BMD than those losing weight in the trochanter and the total hip (p<0.001), and in the femoral neck (p=0.055). Elderly women should be advised to maintain their body weight and participate in physical activity. Despite the large number of variables examined in this study, bone loss occurring with increased age is not thoroughly explained., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this review is to summarize the effectiveness of select vitamins, minerals and trace elements in postmenopausal women for their effects on bone health, cardiovascular health, breast cancer, cognition and vasomotor symptoms., Methods: Review of the relevant literature and results from recent clinical studies, as well as critical analyses of published systematic reviews and meta-analyses were obtained from PubMed and Cochrane Library of Reviews. Vitamin A, the B vitamins, vitamin C, calcium, vitamin D, vitamin E, vitamin K, magnesium, selenium and zinc were selected for review. In circumstances where the vitamin, mineral or trace element has not been studied for a given condition, no information was provided., Results and Discussion: All vitamins, minerals and trace elements play an important role in maintaining health and wellbeing among menopausal women. Adequate dietary intake is essential and supplementation should be considered in women with documented malabsorption syndromes or deficiencies. Based on a review of the literature, supplementation with vitamin C, D, K and calcium can also be recommended for proper maintenance of bone health. The only supplement studied for vasomotor symptoms was vitamin E and this vitamin lacked clinical support. Supplementation in healthy postmenopausal women with vitamins and minerals in diet or pill forms cannot be recommended currently for any other indications., (Published by Elsevier Ireland Ltd.)

Objectives: To develop and validate the Osteoporosis Patient Satisfaction Questionnaire (OPSQ) and to assess the opinion of postmenopausal osteoporotic women towards pharmaceutical care., Methods: A 16-item instrument was designed. Each response consists of a five-point Likert-like scale with higher scores indicating greater satisfaction. The face and content validity was established via consultation with an endocrinologist and three pharmacists as well as feedback from participants in a preliminary study. Postmenopausal osteoporotic women taking bisphosphonates were recruited and randomly allocated to the intervention (n=90) and control groups (n=90). Pharmaceutical care was provided at month 2 to the intervention group while the control group received standard pharmacy services. The OPSQ was administered at month 6 (end of the intervention period), to assess patients' satisfaction. Factor analysis was performed using varimax rotation. Internal reliability was established using Cronbach's alpha. Construct validity was performed by using the Mann-Whitney U test., Results: The internal reliability of the OPSQ produced a Cronbach's alpha of 0.86. Factor analysis identified one component in the OPSQ, which measured patient satisfaction. The intervention group showed significantly better overall OPSQ score than the control group (91.89+/-7.22% versus 84.32+/-7.48%, p<0.001). This indicates that the OPSQ was able to differentiate between participants who received pharmaceutical care from those who did not., Conclusions: The 16-item OPSQ developed in this study has high internal reliability and is a valid instrument for assessing osteoporotic women's satisfaction with pharmaceutical care service in Malaysia.

Background: To analyse prospectively the effect of calcium or calcium+D supplementation on coronary heart disease (CHD) in 52-62-year-old women., Methods and Results: 10,555 52-62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994-2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium+D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium+D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02-1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium+D supplements was 1.26 (95% CI 1.01-1.57)., Conclusions: Calcium or calcium+D supplementation appears to increase the risk of CHD among women before old age.

Context and Objective: Osteoporosis causes an increase in bone fragility. Its clinical significance mainly refers to (hip) fractures secondary to (low or moderate) trauma. In Europe and North America about 6% of men and 21% of women aged 50-84 years are classified to have osteoporosis. Although it is well accepted that exercise is essential for the management of osteoporosis, the exact role of physical activity in the primary and secondary prevention of osteoporotic fractures is still controversial., Methods: The MEDLINE database and reference lists of selected publications were systematically searched for randomized controlled trials and prospective cohort studies, respectively, published since January 2000 regarding the association of physical activity and osteoporosis in postmenopausal women., Results: Two prospective cohort studies indicate the clinical relevance of this association by showing an inverse relationship between physical activity and the risk of hip fracture. There is convincing evidence that physical activity effectively slows bone loss in postmenopausal women in a dose-dependent manner. Exercise programs may increase bone mineral density., Conclusion: In order to maximize the goals of public health most effective, individually adapted, intense, high impact exercise programs are needed. However, they may be complicated to communicate and adherence on the population level may be hard to achieve. These programs must be weighed against popular and applicable existing programs (e.g. aerobic classes, Tai Chi, and walking) which appear to be easier to adhere to but appear to be less effective in the prevention of osteoporotic fractures in the individual postmenopausal women.

Both osteoporosis with fracture and breast cancer are important health issues for postmenopausal women. It is well known that estrogen and estrogen receptors (ERs) play an important role in the pathogenesis of both diseases. In past decades, hormone therapy (HT), mainly estrogen plus progestin (EPT), has been frequently used for the purpose of preventing and treating postmenopausal osteoporosis because of its efficacy, but it also contributes to a significant increase in breast cancer. Currently, there is a dilemma regarding the use of estrogen for postmenopausal women. Fortunately, an increasing understanding of the action of estrogen has led ultimately to the design of new drugs that work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs), and are not only effective in preventing osteoporosis and managing those with osteoporosis, but also in decreasing the incidence of breast cancer. Among these SERMs, raloxifene may be the most attractive agent based on the evidence from five recent large trials (Multiple Outcomes of Raloxifene Evaluation [MORE], Continuing Outcomes Relevant to Evista [CORE], Raloxifene Use for the Heart [RUTH], Study of Tamoxifen and Raloxifene [STAR], and Evista Versus Alendronate [EVA]). The former three trials showed that raloxifene not only decreases the incidence of osteoporosis-associated fractures, but also has efficacy in breast cancer prevention. The head-to-head comparison with the anti-fracture agent alendronate (EVA trial) and the chemoprevention agent tamoxifen (STAR trial) further confirmed that raloxifene is a better choice. We concluded that since there is an absence of a therapeutic effect on relieving climacteric symptoms and there is the presence of a potential risk of thromboembolism in the use of raloxifene, this drug can be prescribed for clear indications, such as the management of osteoporosis, the prevention of fracture, and decreasing the incidence of invasive breast cancer, with careful monitoring for thromboembolism. It is reasonable to use raloxifene as an appropriate medicine that targets climacteric symptom-free postmenopausal women because of its overall favorable risk-benefit safety profile using the global index proposed by the Women's Health Initiation (WHI).

Unlabelled: The available courses of therapy to osteoporosis in menopausal women are limited by several side effects generated. A need therefore arises to explore herbal alternatives that are effective and safe., Objective: Present animal studies were conducted to investigate the potential of Tinospora cordifolia (TC) ethanolic stem extract as an antiosteoporotic agent., Methods: Three-month-old female Sprague-Dawley rats were either ovariectomized (ovx) or sham operated and treated with vehicle (benzyl benzoate:castor oil; 1:4), E(2) (1 microg/day) or TC (10, 50, 100 mg/kg b.wt) subcutaneously for 4 weeks. At the end of experiment bone mineral density of tibiae was measured by quantitative computer tomography. Serum was analyzed for the activity of alkaline phosphatase and levels of osteocalcin, cross-laps and lipids. Uterus and mammary gland were processed for histological studies., Results: Ovx rats treated with TC (10 mg/kg b.wt) showed an osteoprotective effect as the bone loss in tibiae was slower than ovx controls. Serum osteocalcin and cross-laps levels were significantly reduced. All the above effects of TC were much milder than those produced by E(2). Alkaline phosphatase activity was higher in TC treatment groups. Total cholesterol and LDL levels remained unaltered but HDL levels were significantly lowered with TC (50 mg/kg b.wt) treatment. Uterus and mammary gland showed no signs of proliferation after treatment with TC extract., Conclusion: TC extract showed estrogen like effects in bone but not in reproductive organs like uterus and mammary gland. Thus, this study demonstrates that extract of T. cordifolia has the potential for being used as antiosteoporotic agent.

Objective: Natural medicines derived from plants have aroused increasing interest in the prevention and treatment of osteoporosis. This is due to their unique characteristics as these are more suitable for long-term use compared with synthesized chemicals and have apparently fewer adverse effects. Curculigo orchioides (CO) has a long history in the treatment of postmenopausal osteoporosis in traditional Chinese medicine. The present study was designed to investigate the protective effects of ethanol extracts of CO on ovariectomy-induced bone loss., Methods: Sixty female (4.5-month-old) Sprague-Dawley rats were assigned to sham and OVX groups. The OVX rats were further divided into five subgroups treated respectively, with vehicle, nylestriol (1 mg/kg, i.g.) and CO extract (0.5, 1.0, and 2.0 g/kg, i.g.) for 12 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured by peripheral quantitative computerized tomography (pQCT) densitometry. Serum phosphorus, calcium, ACTH, corticosterone, deoxypyridinoline crosslinks to creatinine ratio (DPD/Cr), alkaline phosphate (ALP), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin (OPG), IL-6, and TNF-alpha were also determined., Results: Administration of CO extract prevented bone loss in the trabecular bone of the tibia in ovariectomized rats without affecting the weight of the body and the uterus, and increased serum phosphorus, calcium, and OPG levels, decreased serum DPD/Cr, TRAP, ACTH, and corticosterone levels, but did not alter serum TNF-alpha, IL-6, and ALP levels in ovariectomized rats., Conclusion: CO ethanol extract has a definite protective effect on bone loss in ovariectomized rats by inhibiting bone resorption and increasing serum phosphorus and calcium levels, without affecting bone formation. Therefore, CO can be considered a potential antiosteoporosis herbal plant, although more studies are needed to clarify its real potential chemical constituents and their mechanism of action.

Objectives: The social and economic burden of osteoporosis is important since it concerns a continuously aging population, while the disease is silent until the emergence of fractures. Aim of the study was to assess female population knowledge about osteoporosis risk factors and to identify the risk factors of the studied population., Methods: A sample of 99 (aged: 61.59+/-9.61 years) women under treatment for osteoporosis or osteopenia answered the questionnaire provided by their pharmacists and were included in the study's analysis. Various parameters on osteoporosis awareness and risk factor knowledge of the population sample studied were analyzed., Results: It was revealed that 96% of the participants knew osteoporosis definition and sources of this knowledge were one or more of the following: doctors (86.3%), mass media (20%) and friends or relatives (13.7%). It was found that the older age was associated with less knowledge (OR=0.93, CI: 0.88-0.97, p=0.004), and higher education with increased knowledge (OR=1.68, CI: 1.10-2.55, p=0.014) about osteoporosis. 56.4% of the participants were aware of at least one osteoporosis risk factor. In multivariate analysis, it was revealed that the participants who referred increased milk products consumption in childhood (OR=3.72, CI: 1.34-10.36, p=0.012) and current performance of physical activity (OR=13.06, CI: 3.22-53.05, p<0.001) were more likely to be informed about osteoporosis risk factors; age >61 years was associated with decreased knowledge of risk factors (OR=0.27, CI: 0.09-0.82, p=0.018)., Conclusions: This study implies that a higher degree of participant's health education may result in the avoidance of osteoporosis risk factors. Increasing knowledge of osteoporosis should be a priority for future intervention programs in order to promote specific behavioural strategies for osteoporosis prevention.

Objectives: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women., Methods: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months., Results: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women., Conclusions: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.

Vitamin D is a hormone that controls phosphorus, calcium, and bone metabolism and neuromuscular function. Vitamin D synthesis is a process in which the skin, liver, and kidney are sequentially involved. The vitamin D pool is completed by the amount taken with food and supplements. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes a painful disease, osteomalacia, and increases muscle weakness, which worsens the risk of falls and fractures. A high prevalence of vitamin D insufficiency exists in the apparently healthy population, osteoporotic patients, and patients with prior fractures. Factors contributing to low vitamin D levels include low sunlight exposure, decreased skin synthesis and intestinal absorption, and inadequate diet. The simplest way to correct hypovitaminosis is adequate nutrition and supplements. However, few patients with osteoporosis and/or fractures, receive adequate supplements. Vitamin D insufficiency may alter the regulatory mechanisms of parathyroid hormone and may induce a secondary hyperparathyroidism that increases the risk of osteoporosis and fractures, although the necessary degree of this is not established. Monitoring of serum 25-hydroxyvitamin D levels is the only way to assess vitamin D status. The ideal healthy blood levels of 25-hydroxyvitamin D are controversial, although a range from 30 to 60ng/mL is widely accepted. The role of vitamin D supplementation is to provide humans with the nutrient in an amount closer to the biological norm for our species. This amount of vitamin D results in optimal function of many aspects of health, including balance and muscle strength, thus reducing the risk of fracture beyond what is possible via the quality and quantity of bone itself.

Tibolone has been widely accepted as remedy for vasomotor symptoms and for prevention of bone loss. Studies over the past 25 years have documented its effects on bone mineral density in younger and older women. Tibolone reduces bone turnover substantially (about the same amount as hormone therapy). Increases in bone mineral density (BMD) accompany this reduction in bone turnover, but like all other antiresorptive therapies, reduction in fracture risk (i.e. 50%) is always greater than would be predicted from BMD change. Finally, as with hormone therapies, dosage reductions have been prompted by new evidence of low dosage efficacy and concern over dose-related side effects. Solid evidence has now emerged from large, dose-ranging studies that the 1.25mg tibolone dosage is adequate for preservation of BMD and for reduction of fracture risk. Now that fracture efficacy has been added to the list of tibolone's documented bone benefits, physicians must consider this in the overall risks and benefits of its use.

Objective: A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT)., Methods: Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months., Results: The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss., Conclusion: Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.

Objectives: Current recommendations for hormone therapy (HT) are mainly based on findings from studies using standard dose regimens in older women who had a different health profile from those who start HT soon after the onset of menopause., Methods: We, therefore, reviewed controlled trials assessing the efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT) started for treatment of climacteric symptoms. This review is limited to oral cc-HT regimens over sequential regimens as most postmenopausal women prefer not to have a return of uterine bleeding, and to studies of at least 2 years in duration., Results: Low-dose cc-HT is effective in alleviating climacteric symptoms and in maintaining bone density over prolonged periods, although no data were available regarding fracture risk. No increased risk of coronary heart disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was reported in the long-term studies and no definitive evidence for an increased risk of breast cancer was found. Breakthrough bleeding during the first months of use is less common than with standard dose HT and amenorrhoea is achieved in most women over time. These regimens are safe for the endometrium and are well tolerated, with a low incidence of adverse events compared with standard doses., Conclusions: Current evidence from controlled trials indicates that low-dose oral cc-HT appears effective and safe. This makes it a good choice for the alleviation of climacteric symptoms, and for this purpose long-term administration of low-dose cc-HT does not seem to impose serious health risks. However, more long-term study data and direct head-to-head comparisons between various low-dose preparations are needed to support or rectify the safety aspects.

Objectives: The purpose of this study was to compare the health-related quality of life (HRQoL) of elderly users and non-users of hormone therapy (HT)., Subjects and Methods: Subjects were participants in an ongoing intervention study, which is aimed at elucidating the effectiveness of an educational program in the prevention of osteoporosis. A random sample (n=4200) of the female population in Southern Finland within the age group of 60-70 years was drawn from the population register and invited to take part in the trial; 2181 (52%) accepted the invitation and were randomized either to the educational program or to a control group. In 2002 all 2181 participants were asked by a postal survey about HRQoL (generic15D), education, profession, climacteric symptoms, use of HT, chronic diseases and medication. Of the 1663 respondents (76% of the participants; 40% of the original cohort) 585 (mean age 67.5 years) were HT users and 1078 (mean age 68.9 years) non-users., Results: After standardizing for age, education, number of continuous medication and ongoing diseases HRQoL of HT users was significantly better on the dimensions of usual activities, vitality and sexual activity. The effect of HT on overall HRQoL on a 0-1 scale was positive, but neither statistically significant nor clinically important. The number of medication and diseases had a statistically significant negative effect, but higher education a positive, but statistically non-significant effect on HRQoL overall., Conclusions: Among elderly women HT use has a statistically significant positive effect on some dimensions of HRQoL, but not on HRQoL overall. To improve HRQoL is not an indication for elderly postmenopausal women to use HT.

Objective: The objective of this study was to evaluate gynecologists' knowledge of the WHI study, and its repercussions on their attitudes and practice 3 years after publication., Design: A self-administered, anonymous questionnaire containing 19 questions was sent to 6000 gynecologists, members of the São Paulo Society of Obstetrics and Gynecology., Results: The response rate was 24.2% (1453 completed questionnaires) with a sample error of 2.23% and confidence level of 95%. Although 95.9% of the respondents were aware of the WHI study, only 24.4% knew of all the other studies mentioned (HERS I, HERS II and Million Women Study). Although 84.6% stated that the results of the WHI study could not be extrapolated to other forms of HT, 23.1% and 25.2%, respectively, stopped prescribing CEE or MPA, 63.7% decreased the dose, 55.2% opted for drugs such as bisphosphonates, tibolone and SERMS, and 46.3% began to prescribe tranquilizers, isoflavone and other natural medications. Moreover, 59.2% agreed that HT should be used for only 4-5 years. Prescriptions decreased significantly for all indications (p<0.0001). The principal reason for physicians to discontinue HT in a patient was increased risk of breast cancer (62.3%), whereas, according to the physicians, the most important factor for the patients was fear of HT (80.3%)., Conclusion: A high percentage of gynecologists in this study knew of the WHI study and followed its recommendations concerning cardiovascular prevention; consequently they changed their management of the treatment of postmenopausal women by restricting indications for HT and decreasing its duration of use and dose.

Objective: The aim of the current study was to examine whether a diet rich in dairy products followed by a nutrition education program for the prevention of osteoporosis could have any adverse effect on certain cardiovascular disease (CVD) risk factors over a 5-month intervention period., Methods: A total sample of 82 women (55-65 years old) was randomized to a dietary intervention group (IG: n=42), attending biweekly nutrition education program and provided with low-fat, fortified dairy products and to a control group (CG: n=40). Changes in dietary, biochemical and clinical indices related to CVD were determined at the end of the 5-month intervention period., Results: The IG was found to have a higher decrease in the percentage of energy intake derived from total fat and a higher increase in the intake of calcium, phosphorus, magnesium and potassium compared to the CG (p<0.05). Furthermore, the IG subjects were found to have a lower increase in BMI (0.7+/-0.1 versus 1.4+/-0.2 Kg/m(2), p=0.011) and systolic blood pressure (SBP) (2.5+/-2.9 versus 7.8+/-2.2 mmHg, p=0.040) and a higher decrease in serum total cholesterol (-5.2+/-3.3 versus 6.9+/-5.1 mg/dl, p=0.042) and LDL-cholesterol levels (-20.0+/-2.6 versus -12.4+/-4.2 mg/dl, p=0.034) compared to the CG., Conclusions: The findings of the current study indicate that a dietary intervention aiming to minimize the risk for osteoporosis did not have any adverse effects on CVD risk factors. On the contrary, it has induced favourable changes in BMI, serum lipids and SBP.

Objectives: To study the fracture reducing potential of hormone replacement therapy (HRT) at a population level, the effect of age on the fracture reducing potential of HRT, and to examine whether socio-economic factors confound the effects of HRT on fracture risk., Subjects and Methods: Case-control study. All women who sustained any fracture during the year 2000 in Denmark served as cases (n=64,548). For each case, three age-matched controls were randomly drawn from the background population (n=193,641). The main exposure was the average daily dose of HRT (expressed as defined daily doses DDD/day). Adjustments were made for co-morbidity, socio-economic factors, and prior fracture., Results: A fracture risk reduction was seen in women aged>or=50 years using >or=0.3 DDD/day. The risk reduction for any fracture was larger in women aged>or=60 years (0.3-0.99 DDD/day: odds ratio (OR)=0.77, 95% confidence intervals (CI): 0.73-0.82, >or=1 DDD/day: OR=0.61, 95% CI: 0.56-0.67) than in women aged 50-59 years (0.3-0.99 DDD/day: OR=0.92, 95% CI: 0.85-0.99, >or=1 DDD/day: OR=0.77, 95% CI: 0.70-0.84). Larger risk reductions were seen for Colles' fractures (age 50-59 years: OR=0.64 for 0.3-0.99 DDD/day, and OR=0.57 for >or=1 DDD/day, age>or=60 years: OR=0.52 for 0.3-0.99 DDD/day, and OR=0.40 for >or=1 DDD/day). Adjustment only changed the estimates little. No difference between oral and dermal preparations could be found., Conclusions: Hormonal replacement therapy possesses a fracture-reducing potential at population level even at dosages lower than usually recommended. The risk reduction was larger with advancing age for any fracture and Colles' fractures.

Unlabelled: Tibolone is used in postmenopausal women to alleviate menopausal symptoms and to prevent osteoporosis, but it does not stimulate the endometrium and the breast. Up to date, little data are available on the effect of tibolone on breast cancer initiation and progression., Objective: In the present in vitro study, we investigated the effect of tibolone and its metabolites (3alpha-OH tibolone, 3beta-OH tibolone, the Delta4 isomer and the sulphated isoform) on invasion of human breast cancer cells., Methods: The effect on invasion was evaluated in the chick heart invasion assay using MCF-7/6 cells and in the collagen type I invasion assay using T47-D cells. Furthermore, the compounds were tested in aggregation and migration assays., Results: We observed that, at a concentration of 100 microM, tibolone and its 3beta-OH metabolite possess anti-invasive activities in the two different invasion assays. However, this was neither due to effects on cell-cell adhesion nor on motility. In an attempt to probe the mechanism underlying the anti-invasive effect, we found that pro-MMP-9 release was markedly reduced in the supernatant of MCF-7/6 breast cancer cells treated with tibolone, 3alpha-OH tibolone and the Delta4 isomer but, interestingly, not with the sulphated metabolite., Conclusion: We conclude that tibolone and its 3beta-OH metabolite have an anti-invasive effect on the tested breast cancer cell lines in vitro. This effect on invasion is not correlated with an effect on cell-cell adhesion or motility but coincides with a decreased release of pro-MMP-9 in the medium.

Objectives: To evaluate the pattern of mineral density in eumenorrhoic and oligomenorrhoic perimenopausal women, and assess the effects of different low dose oral contraceptives (OC) on bone metabolism and spine bone density., Methods: Spine bone density was evaluated in a longitudinal 2-year follow-up, randomized, unblinded, uncontrolled clinical trial conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrhoic women and in perimenopausal oligomenorrhoic women treated with an oral contraceptive containing 20 microg ethinyl estradiol plus 0.15 mg desogestrel, 0.100 mg levonorgestrel, 0.75 mg of gestodene (n=15 in each group). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate., Results: During the observation period, in normal menstruating women there were no changes in menstrual cycle, plasma FSH and estradiol levels, and spine bone density. In oligomenorrhoic untreated women an increase in cycle length, with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were evidenced (p<0.05). In this group a significant decrease in bone density (p<0.05) occurred. In OC-treated women, a significant (p<0.05) increase in bone density was observed, with no differences among different groups., Conclusion: Different progestins used in OC preparations do not modify the bone sparing effect of perimenopausal OC administration avoiding the decrease in bone density.

Oral daily bisphosphonates carry a potential for gastrointestinal (GI) adverse events, which has been partly addressed by introducing once-weekly regimens. Nevertheless, the need to follow inconvenient dosing instructions every week could still hinder long-term compliance and therapeutic outcome. In addition, survey data indicates that many patients would prefer a once-monthly rather than once-weekly bisphosphonate dosing regimen. Ibandronate is a potent, nitrogen-containing bisphosphonate specifically developed for less frequent administration. In a pivotal study in postmenopausal osteoporosis, oral ibandronate, administered daily or with a between-dose interval of >2 months, demonstrated robust antifracture efficacy and an overall incidence of upper GI adverse events similar to placebo, even in patients at increased risk of such events. This and other clinical studies conducted in postmenopausal women demonstrate that oral ibandronate has an excellent upper GI safety profile.

Objectives: To assess and compare various approaches for selecting women for a bone mineral density (BMD) examination in three different age groups: (1) the most commonly recommended strategy, i.e., selection based on the presence of at least one major risk factor for osteoporosis (personal history of fracture, maternal history of hip fracture, low weight, early menopause), (2) by weight, and (3) calculation of an individual risk score based on the predictive equation (logistic regression model) including the factors most predictive of osteoporosis in each age group., Methods: Data from three population-based samples of postmenopausal women of different ages 60-70 years (n=399), 70-80 years (n=392), and 80 years or older (n=3628). Within each age group, the value of these different approaches was primarily assessed in terms of their discriminant value (sensitivity and positive predictive value (PPV)) for osteoporosis. Other women besides osteoporotic women might also be considered at high risk of fracture (and hence treated), in particular osteopenic women (T-score<-1.5) with multiple risk factors for fracture. Hence, we also estimated and compared the overall number of selected women who might be considered at high risk of fracture after BMD testing, according to selection criteria., Results: In each age group and classifying a similar percentage of women at high risk, use of weight as a tool for identifying osteoporotic women has a higher sensitivity and PPV than the currently recommended approach. Increasing the cutoff for weight increases sensitivity. However, identifying the majority (around 80%) of all osteoporotic women requires testing more than half the population. Combining weight with other factors into more complex risk scores usually does not significantly improve the discriminant value of the assessment. When similar percentages of women are selected, more women with osteopenia and multiple risk factors are identified when selection is based on usual referral criteria. However, since more osteoporotic women are identified after selection by weight (higher PPV for osteoporosis), the overall number of women who might be considered at high risk of fracture after BMD testing is higher after selection by weight., Conclusions: In each age group considered, selecting women for BMD testing based on weight is the simplest and most effective screening method for identifying osteoporotic women as well as other subgroups of women who might also be considered to be at high risk of fracture.

Objectives: Intestinal bacterial metabolize the soy isoflavone daidzein to O-desmethylangolensin (O-DMA) or equol. Some individuals do not excrete O-DMA or equol after soy consumption, suggesting they do not harbor bacteria capable of producing these metabolites. The aim of this study was to evaluate bone mineral density (BMD) in relation to presence of these urinary metabolites., Methods: BMD, determined by whole-body dual X-ray absorptiometry scan, was age-adjusted and evaluated in relation to O-DMA-producer and equol-producer phenotypes in 92 postmenopausal women, aged 50-75 years. Women consumed supplemental soy foods (daidzein source) for 3 days and collected a first-void urine sample on the fourth day in order to determine metabolic phenotypes., Results: In O-DMA producers (n=76) compared to O-DMA non-producers (n=16), greater total, leg and head BMD (p<0.05) were observed. Total BMD among the O-DMA producers (geometric mean=1.04 g/cm2) was 6% greater than total BMD among the O-DMA non-producers (geometric mean=0.98 g/cm2). Total and site-specific BMD did not differ between equol producers (n=24) and non-producers (n=68) (p>0.05). In exploratory analyses, among regular soy consumers, spinal BMD was 20% lower among the equol producers than non-producers, whereas, among soy non-consumers, no such difference was observed (p-interaction<0.05). Among equol producers, circulating estrone and free estradiol concentrations were inversely or not associated with total BMD, whereas, among equol non-producers, these hormones were positively associated (p-interaction<0.05)., Conclusions: Our results provide evidence that intestinal bacterial composition may influence BMD in postmenopausal women. Further studies characterizing associations of intestinal bacterial profiles with BMD are warranted.

Objective: Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT., Methods: Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months., Results: BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported., Conclusion: Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.

Women make up 55% of the total world population. This percentage is set to steadily increase over the next three decades. Europe also has the highest proportion of older women in the world. In fact, there are now approximately 3 women for every 2 men over 65. All of this data confirms the importance of prevention. An ideal approach for the female post-menopausal population would be treatment of any condition that can improve physical, mental and social well-being. Nevertheless, it is understood that the efficacy and cost/benefits of every screening programme need to be analysed. One of the largest and most neglected groups that could benefit from prevention consists of women without hot flushes (asymptomatic women), but with risk factors. The strategic measures are information, research and development of programmes. The more practical approach would be to identify patients and therefore yield better results in terms of health status and improvement. Statistics show that the three main causes of mortality and disability in developed countries for post-menopausal women are cardiovascular disease (CVD), cancer and osteoporosis-associated fractures. There are agreed recommendations to include some preventive measures for these three disorders in clinical practice for health professionals, at least at the minimal level. Research into the role that other diseases play will allow strategies to be developed in order to enhance prevention. Disorders such as urinary incontinence, dyspareunia, visual and hearing impairment and cognitive dysfunction are seen in significant percentages in post-menopausal women and may affect their quality of life. Health care professionals should bear in mind that many women may be reluctant to raise questions about some disorders spontaneously. Physicians should therefore search for patients with risk factors for these diseases. Prevention and treatment to avoid medical accidents will improve the quantity and quality of life.

To consider what a correct preventive approach for osteoporosis should be in the management of the asymptomatic post-menopausal woman. Literature review and opinions on this issue shared by a group of professionals with wide clinical experience in health care for peri- and post-menopausal women. There is agreement that osteoporosis combines most of the ideal requirements for the application of a preventive strategy. The natural evolution of this pathology leads to serious events, fractures, but it provides various opportunities for prevention. Osteoporosis can be avoided and in particular, fractures due to bone fragility and their consequences should be avoided. Nowadays, there are different courses of action (pharmacological or otherwise) with proven effectiveness for the prevention osteoporosis and osteoporotic fractures. However, long-term action is required for a broad segment of the population, so a certain strategy is necessary to guide clinical decisions for different profiles of women. There is little data in the literature to justify a different preventive approach, depending on the presence or absence of vasomotor symptoms, but clinical experience shows that their absence is not associated with a lower osteoporosis risk. Different strategies have been tried for the prevention of osteoporosis and its complications and some of them might be effective, but there is no analysis with conclusive results. A preventive strategy for osteoporosis should be included in the management of asymptomatic post-menopausal women, because this is an avoidable pathology and the absence of vasomotor symptoms does not reduce the risk of its development. Nevertheless, a well-designed cost-benefit analysis is needed to justify the implementation of any strategy at a community level, because adverse effects and economic cost could exceed the benefits obtained in low fracture risk populations.

The age at which menopause occurs is a critical factor in the magnitude of its consequences. Most of the medium-to-long-term effects of oestrogen deprivation depend on their duration. The timing of the last menstruation is therefore important, but hypoestrogenic amenorrhoea during the reproductive age is also a relevant factor in the evaluation of individual risks. In recent years, moving post-menopausal women from the lowest point of ovarian hypofunction has been the most important motivation for developing guidelines for the hormonal management of menopause. However, recent data suggest that this may be associated with an unacceptable increase in morbidity in a number of women. Concerns about long-term hormone replacement therapy (HRT) at menopause have recently enhanced interest in a group of molecules that act on the oestrogen receptor with selective effects, known as selective oestrogen receptor modulators (SERMs). Of these, Raloxifene has been approved for the treatment and prevention of osteoporosis, and exhibits a pattern of actions particularly well matched to the needs and concerns of post-menopausal women. Further studies on SERMs may open up new vistas in patient-specific management of post-menopausal health. Finally, debates on the specific health consequences of menopause deal mainly with the risk of chronic disease. Gynaecologists and other health professionals would be advised to develop intervention strategies at menopause according to the continuum of a woman's life, beginning at the post-menarche and extending into later life.

Objectives: To estimate the number of women aged 50-69 years treated by hormone therapy (HT) in France before Women's Health Initiative's (WHI) results and to evaluate the potential decrease of HT prescriptions since the publication of WHI clinical trial., Methods: We used data from eight computerized databases of French cohort studies providing information on HT and constituted by women aged over 50 years living in metropolitan France. From these, we used direct standardization on the French population to estimate the prevalence of HT users across 5 years age groups. Data from the National Health Insurance Agency on two time-periods November 2002-January 2003 and November 2003-January 2004 were used to evaluate the evolution of HT prescriptions since WHI's publication among women aged 50-69 years living in the Rhône-Alpes region., Results: The crude prevalence of HT users among women aged 50-69 years was 52.3% (51.8-52.8) and corresponds to a standardized prevalence of 35.7% (35.1-36.4), that is about 2.56 (2.51-2.59) million women. Standardized prevalence was the highest in 50-54 years age group then it decreased significantly across the older age groups (p<10(-6)). HT reimbursements decreased significantly between the two studied time-periods in the Rhône-Alpes region (p<10(-6)) from -14 to -45%, depending on the considered age groups (65-69 or 50-54 years)., Conclusions: Although WHI results have been criticized by French professional societies based on the fact that treatments used were different in France--mainly transdermal estrogens--and that French postmenopausal women were at lower vascular risk than those of the WHI, the release of this study had effect on the prescription before the French regulatory agency (AFSSAPS) edited limiting recommendations for HT prescription. Further efforts have to be made to collect systematically information on preventive treatments used at menopause followed by evaluation studies.

Objectives: Following the results of recent randomized controlled trials on the risks and benefits of the long-term use of hormonal therapy (HT), practice guidelines regarding HT use have been revised. The aim of the study is to assess the prevalence and the correlates of HT use in Israel in 2003., Methods: This is a cross-sectional study, conducted on a representative sample of the general population in Israel aged 21 years and over. The study questionnaire is based on the European Health Interview Survey (EUROHIS) project, aimed to develop uniform study tools, to enable international comparisons. The current module of the survey focused on women's health, and telephone interviews were conducted with 1396 women by trained interviewers in the year 2003., Results: Out of a total of 1396 participants, 535 were defined as peri- or postmenopausal (38%). Of them, 9.9% were currently using HT (11.7% and 2.9% among the Jewish and Arab participants, respectively), and their mean age (S.D.) was 57.7 (6.5) years. Mean duration of HT use was 8.0 (5.5) years. Treatment of menopausal symptoms was the most common reason for HT use (69.2%). Significant correlates of HT use were age, being secular and having seen a gynecologist in the previous 12 months., Conclusions: Current HT use rates reported are lower than those reported 3 years ago for Israeli women. Awareness of both physicians and patients to the WHI results (2002), may have accounted for this trend, at least partially.

It is generally accepted, that raloxifene administration does not have adverse effects on the uterus. We report the cases of two relatively young postmenopausal patients, who presented with vaginal bleeding, due to endometrial pathology, approximately 1 year after the initiation of raloxifene administration. The women were 43 and 44 years old, and received 60 mg/day of oral raloxifene for 11.5 and 10.5 months, respectively. In both cases, raloxifene was given for osteoporosis prevention in the absence of vasomotor symptoms. The first patient underwent Pipelle-biopsy and hysteroscopy with histopathology revealing simple endometrial hyperplasia. The second patient underwent hysteroscopy with removal of an endometrial polyp, with no histopathological signs of malignancy. Continuation of raloxifene administration was decided in both cases, and follow-up did not reveal any sign of recurrence. Uterine bleeding may rarely occur in postmenopausal women under raloxifene therapy. Patients should be encouraged to report bleeding or spotting and appropriate diagnostic and therapeutic management should follow as in any other case.

Osteoporosis is a common condition in postmenopausal women and is associated with significant healthcare costs, morbidity and mortality. It is clear that long-term hormone replacement therapy (HRT) has a role to play in preventing osteoporosis by increasing bone mineral density and reducing fracture rate. It is important that these benefits, as well as those on climacteric symptoms, quality of life, colorectal carcinoma and cognition, are not underestimated in the face of the postulated risks with regard to breast cancer and cardiovascular disease. In conclusion, HRT should currently be used only for women with climacteric symptoms or an increased risk of osteoporosis, and it is important that there is an individualised approach to treatment based on each woman's risk profile.

The fourth Amsterdam Menopause Symposium (2-4 October 2004) was dedicated to practical recommendations to guide clinicians after the confusion, concerns, and controversies generated by study results over the previous several years. Those recommendations are summarized in this deliberately concise and user-friendly document, always recognizing that each clinician must help women with their decision-making according to individual needs, desires, and understanding of benefits and risks.

The HRT field has been dramatically affected by the publication on major randomised controlled trials of the long-term effects of HRT. The publicity surrounding the publication of these data has affected public and regulatory perceptions of HRT and its role in healthcare, including the relatively short-term use of HRT for the relief of menopausal symptoms. An evidence-based appraisal of the role of HRT today is best achieved by considering the different components of the effects of HRT individually, based on the best trial evidence, and then considering these together in the context of the age of woman concerned and the specific components relevant to that woman's health profile. This paper summarises the effects of HRT using this approach in the context of European practice today and describes the events surrounding the regulatory and scientific society position statements.

Aim: To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis., Methods: 212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S.D. of the premenopausal mean value) postmenopausal women aged 45-65 years participated in a 2-year prospective study. Treatments were 45 microg 17beta-estradiol combined with 30 (n = 69) or 40 microg (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day patch. All received a daily supplement of 500 mg calcium. BMD at lumbar spine (L2-L4), hip and total body, as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase (sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured regularly., Results: BMD at the lumbar spine, hip and total body increased by 8, 6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from baseline (all P < 0.001)), except for uCa that did not change significantly. No significant dose-related effect of levonorgestrel was found. Vaginal bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the study period. Skin tolerance was good in 84% of the women with no difference between the study groups. No incidences of endometrial hyperplasia, uterine or mammary cancer occurred., Conclusion: The transdermal combination of 17beta-estradiol and levonorgestrel has a positive effect on BMD in an osteopenic postmenopausal population. Furthermore, a high safety profile was observed.