Age at natural menopause and life expectancy with and without type 2 diabetes.

OBJECTIVE: Effective interventions of future health care require a better understanding of the health risks associated with early onset of menopause and diabetes, but the necessary data are scarce. Little quantitative information is available about the combined association of early menopause and diabetes on life expectancy and the number of years lived with and without diabetes. METHODS: We included 3,650 postmenopausal women aged 45+ years from the Rotterdam Study, a prospective population-based cohort study. Age at menopause categories were defined as follows: early (≤44 y old), normal (45-54 y old), and late (≥55 y old). For life table calculations, we used prevalence, incidence rates, and hazard ratios for three transitions (free of diabetes to diabetes, free of diabetes to death, and diabetes to death) stratifying by age at menopause categories and adjusting for confounders. RESULTS: Compared with late menopause, the difference in life expectancy for women who experienced early menopause was -3.5 (95% CI, -6.6 to -0.8) years overall and -4.6 (95% CI, -8.9 to -0.9) years without diabetes. Compared with age at normal menopause, the difference in life expectancy for women who experienced early menopause was -3.1 (95% CI, -5.1 to -1.1) years overall and -3.3 (95% CI, -6.0 to -0.6) years without diabetes. CONCLUSIONS: Women who experienced early menopause lived less long and spent fewer years without diabetes than women who experienced normal or late menopause.

Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis.

Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15-4.52) for CHD incidence, 2.09 (95% CI 1.51-2.89) for stroke incidence, 2.76 (95% CI 1.62-4.71) for CVD mortality and 2.22 (95% CI 1.92-2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67-0.80) for overall CVD, 0.71 (95% CI 0.67-0.75) for CHD, 0.77 (95% CI 0.70-0.85) for stroke, 0.70 (95% CI 0.58-0.84) for CVD mortality and 0.71 (95% CI 0.65-0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56-0.91) for CHD, 0.63 (95% CI 0.57-0.71) for CVD mortality and 0.80 (95% CI 0.76-0.84) for all-cause mortality. For women with BMI 30-35 kg/m2 the risk was 1.67 (95% CI 1.24-2.25) for CHD and 2.3 (95% CI 1.56-3.40) for CVD mortality, compared to normal weight. Each 5 kg/m2 increase in BMI was associated with 24% (95% CI 16-33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.

High Androgens in Postmenopausal Women and the Risk for Atherosclerosis and Cardiovascular Disease: The Rotterdam Study.

Context: Polycystic ovary syndrome (PCOS) is closely linked to hyperandrogenism (HA). In PCOS, HA has been associated with metabolic disturbances that increase the risk for cardiovascular disease (CVD). Objective: To assess the association of high serum androgen levels, as a postmenopausal remnant of PCOS, with the prevalence of atherosclerosis and incidence of CVD in postmenopausal women. Design: The Rotterdam Study, a prospective population-based cohort study. Median follow-up was 11.36 years. Setting: General community. Participants: A total of 2578 women aged >55 years. Exclusion criteria were missing informed consent or follow-up data, perimenopausal status, and menopause by surgical intervention or at an unnatural age (age <40 or >62). Intervention: None. Main Outcomes and Measures: Linear, logistic, and Cox regression models assessed the association of top quartiles (P75) of serum testosterone, free androgen index (FAI), dehydroepiandrosterone, and androstenedione and sex hormone-binding globulin with coronary artery calcium, carotid intima-media thickness (IMT), pulse wave velocity, peripheral artery disease, and incidence of coronary heart disease (CHD), stroke, and CVD. Results: Mean age (standard deviation) was 70.19 (8.71) years, and average time since menopause was 19.85 (9.94) years. Highest quartile FAI was associated with higher pulse wave velocity (ß [95% confidence interval (CI)], 0.009 [0.000 to 0.018]). Highest quartile dehydroepiandrosterone [ß (95% CI), -0.008 (-0.015 to -0.001)] and androstenedione [ß (95% CI), -0.010 (-0.017 to -0.003)] levels were associated with a lower IMT. We found no association between high androgen levels and incident stroke, CHD, or CVD. Conclusion: Postmenopausal high androgen levels were not associated with an elevated risk for CVD. Cardiovascular health in women with PCOS might be better than was anticipated.

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study.

AIMS/HYPOTHESIS: In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators. METHODS: We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40-44 years; normal, 45-55 years; and late menopause, >55 years [reference]). Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits. HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens. RESULTS: During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes. After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (p trend <0.001). The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association. CONCLUSIONS/INTERPRETATION: Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women.

Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis.

It remains unclear whether endogenous sex hormones (ESH) are associated with risk of type 2 diabetes (T2D) in women. Data of 3,117 postmenopausal women participants of the Rotterdam Study were analyzed to examine whether ESH and sex hormone-binding globulin (SHBG) were associated with the risk of incident T2D. Additionally, we performed a systematic review and meta-analysis of studies assessing the prospective association of ESH and SHBG with T2D in women. During a median follow-up of 11.1 years, we identified 384 incident cases of T2D in the Rotterdam Study. No association was observed between total testosterone (TT) or bioavailable testosterone (BT) with T2D. SHBG was inversely associated with the risk of T2D, whereas total estradiol (TE) was associated with increased risk of T2D. Similarly, in the meta-analysis of 13 population-based prospective studies involving more than 1,912 incident T2D cases, low levels of SHBG and high levels of TE were associated with increased risk of T2D, whereas no associations were found for other hormones. The association of SHBG with T2D did not change by menopause status, whereas the associations of ESH and T2D were based only in postmenopausal women. SHBG and TE are independent risk factors for the development of T2D in women.

Design of a frailty index among community living middle-aged and older people: The Rotterdam study.

OBJECTIVES: To design a frailty index (FI) and evaluate three methods to handle missing data. Furthermore, we evaluated its construct (i.e., skewed distribution, correlation with age and sub-maximum score) and criterion validity (based on mortality risk). STUDY DESIGN: We included 11,539 participants (45± years) from a population-based cohort in the Netherlands. Frailty was measured with a FI, which we constructed based on the accumulation of 45 health-related variables, related to mood, cognition, functional status, diseases and conditions, biomarkers, and nutritional status. A total FI-score was calculated by averaging the scores of the deficits, resulting in a score between 0 and 1, with higher scores indicating increasing frailty. Mean imputation, single- and multiple imputation were applied. MAIN OUTCOME MEASURE: Mortality data were obtained by notification from the municipal administration. Median follow-up time was 9.5 years, during which 3902 (34%) participants died. RESULTS: The median FI for the full population was 0.16 (IQR=0.11-0.23). The distribution of the FI was slightly right-skewed, the absolute maximum score was 0.78 and there was a strong correlation with age (Pearson correlation=0.52;95%CI=0.51-0.54). The adjusted HR per unit increase in FI-score on mortality was 1.05 (95%CI=1.05-1.06). Multiple imputation seemed to provide more robust results than mean imputation. CONCLUSION: Based on our results we advise to the use of at least 30 deficits from different health domains to construct a FI if data are not imputed. Future research should use the continuous nature of the FI to monitor trajectories in frailty and find preventive strategies.

Happiness, rather than depression, is associated with sexual behaviour in partnered older adults.

Background: The relation between positive psychological well-being (PPWB) and sexual behaviour is understudied in older adult groups. Objective: To examine the relation between PPWB (positive affect and life satisfaction) and sexual behaviour (sexual activity and physical tenderness) in older adults, and whether it is independent from depressive symptoms and uniform across older age groups. Design: Cross-sectional. Setting: Community-dwelling adults aged 65 years or older, Rotterdam, The Netherlands. Methods: Sexual behaviour, the Cantril Self-Anchoring Striving Scale, the Center for Epidemiological Studies Depression (CES-D) scale and partner status were assessed in 2,373 dementia-free older adults from the Rotterdam Study. Results: For partnered participants, greater positive affect and life satisfaction was associated with more sexual activity and physical tenderness. Although CES-D was negatively associated with sexual behaviour within partnered older adults, there was no association between the negative affect sub-scale and sexual behaviour. The relations were independent of depressive symptoms, physical health and chronic disease status and were observed for both sexes at all older ages. For unpartnered participants, greater life satisfaction and was associated with more physical tenderness. There was low prevalence of sexual behaviour in unpartnered participants, limiting further stratification. Conclusion: Greater PPWB was associated with more sexual behaviour in partnered, community-dwelling older adults. We are the first to demonstrate that sexual behaviour is associated with PPWB, rather than lack of depressive symptoms; and that the association was present at all ages for partnered older adults. Limited conclusions can be drawn for unpartnered older adults as their sexual behaviour was infrequent.

Development of a Healthy Aging Score in the Population-Based Rotterdam Study: Evaluating Age and Sex Differences.

OBJECTIVES: To develop a healthy aging score (HAS), to assess age and sex differences in HAS, and to evaluate the association of the HAS with survival. DESIGN: Prospective population-based cohort. SETTING: Inhabitants of Ommoord, Rotterdam, The Netherlands. PARTICIPANTS: A total of 1405 men and 2122 women, mean (standard deviation) age 75.9 (6.4) years. MAIN MEASURES: We included 7 domains in the total score of HAS: chronic diseases, mental health, cognitive function, physical function, pain, social support, and quality of life; each scored 0, 1, or 2 in each domain. A total score (range 0-14) was constructed and was assessed continuously and in tertiles (13-14: healthy aging, 11-12: intermediate aging, 0-10: poor aging). Sex-specific change in the mean HAS was computed for the age categories of 65-69, 70-74, 75-79, 80-84, and ≥85 years. The association between HAS and mortality was assessed with Cox proportional hazards models. RESULTS: Mean follow-up was 8.6 (3.4) years. Men had poorer scores in the chronic disease domain than women. However, women had poorer mental health, worse physical function, more pain, and lower quality of life compared with men. The prevalence of healthy aging was higher in men (n = 396, 28.2%), than in women (n = 526, 24.8%). The mean (standard deviation) HAS was 11.1 (2.2) in men and 10.7 (2.3) in women. Mean HAS was higher in men than in women for all age categories. The ß for change in mean HAS across the 5 increasing age categories was -0.55 (-0.65 to -0.45) in men and -0.65 (-0.73 to -0.57) in women. The age-adjusted hazard ratio per unit increase in HAS with mortality was 0.86 (0.83-0.89) in men, and 0.89 (0.87-0.91) in women. CONCLUSIONS: Levels of HAS were lower in women compared with men, in all age categories. The HAS declined with increasing age for both sexes, albeit slightly steeper in women. The HAS was strongly associated with mortality in both sexes. A better understanding of population healthy aging and sex differences in this regard could aid to implement strategies for sustainable healthcare in aging populations.

Fertile lifespan characteristics and all-cause and cause-specific mortality among postmenopausal women: the Rotterdam Study.

OBJECTIVE: To characterize the relation between established and previously unexplored characteristics of the fertile life with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 4,076 postmenopausal women. INTERVENTION(S): Women's fertile lifespan (age at menarche to menopause), number of children, maternal age at first and last child, maternal lifespan (interval between maternal age at first and last child), postmaternal fertile lifespan (interval between age at last child and menopause), lifetime cumulative number of menstrual cycles, and unopposed cumulative endogenous estrogen (E) exposure. MAIN OUTCOME MEASURE(S): Registry-based all-cause and cause-specific mortality. RESULT(S): A total of 2,754 women died during 14.8 years of follow-up. Compared with women with 2-3 children, a 12% higher hazard of dying was found for women having 1 child (hazard ratio [HR], 1.12; 95% confidence interval [CI] 1.01-1.24), which became nonsignificant in models adjusted for confounders (HR, 1.08; 95% CI 0.96-1.21). Late age at first and last birth were associated with a 1% lower hazard of dying (HR, 0.99; 95% CI 0.98-1.00). Longer maternal and postmaternal fertile lifespan (HR 1.01; 95% CI 1.00-1.02), longer fertile lifespan (HR 1.02; 95% CI 1.00-1.05), and unopposed cumulative E exposure (HR, 1.02; 95% CI 1.00-1.04) were significantly harmful for all-cause mortality. Findings differed with regard to direction, size, and statistical significance when stratifying for cardiovascular disease, cancer, and other mortality. CONCLUSION(S): Overall, we found that late first and last reproduction were protective for all-cause mortality, whereas a longer maternal lifespan, postmaternal fertile lifespan, and E exposure were harmful for all-cause mortality. More research is needed in contemporary cohorts with larger sample sizes and more extreme ages of birth.

Maternal weight status, diet, and supplement use as determinants of breastfeeding and complementary feeding: a systematic review and meta-analysis.

CONTEXT: Infant feeding practices are influenced by maternal factors. OBJECTIVE: The aim of this review is to examine the associations between maternal weight status or dietary characteristics and breastfeeding or complementary feeding. DATA SOURCES: A systematic literature search of the Embase, Cochrane Library, Google Scholar, MEDLINE, PubMed, and Web of Science databases was performed. STUDY SELECTION: Interventional and cohort studies in healthy mothers and infants that reported on maternal weight status, diet, or supplement use were selected. DATA EXTRACTION: Outcomes assessed included delayed onset of lactogenesis; initiation, exclusivity, duration, and cessation of breastfeeding; and timing of complementary feeding. DATA ANALYSIS: Eighty-one studies were included. Maternal underweight, diet, and supplement use were not associated with infant feeding practices. Obese women had a relative risk of failure to initiate breastfeeding (risk ratio [RR] = 1.23; 95%CI, 1.03-1.47) and a delayed onset of lactogenesis (RR  =  2.06; 95%CI, 1.18-3.61). The RR for breastfeeding cessation was 1.11 (95%CI, 1.07-1.15) per increase in category of body mass index. CONCLUSIONS: Prevention of obesity in women of reproductive age, as well as counseling of obese women after delivery, could be targeted to improve infant feeding practices.

The functions of estrogen receptor beta in the female brain: A systematic review.

Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERß) has been suggested as a therapeutic target. However, little is known about the role of ERß in the female brain. Six electronic databases were searched for articles evaluating the role of ERß in the female brain and the influence of age and menopause on ERß function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERß phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERß may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERß, future studies should be conducted in humans to further our understanding of the importance of ERß in women's mental and cognitive health.

Sex Steroids, Sex Hormone-Binding Globulin and Cardiovascular Health in Men and Postmenopausal Women: The Rotterdam Study.

CONTEXT: The concept of cardiovascular health was recently introduced. Sex steroids and sex hormone-binding globulin (SHBG) influence different health domains, but no studies assessed their role in cardiovascular health. OBJECTIVE: To assess the association between estradiol (E2), testosterone (T), SHBG, and free androgen index (FAI) with cardiovascular health. DESIGN, SETTING, AND PARTICIPANTS: Analyses included 1647 men (68.6 y) and 1564 naturally postmenopausal women (69.6 y) with available data on sex steroids and cardiovascular health from the population-based Rotterdam Study. EXPOSURES: E2, T, SHBG, and FAI. OUTCOME: To define cardiovascular health, 7 metrics including 3 health factors (total cholesterol, fasting glucose, and blood pressure) and 4 health behaviors (physical activity, smoking, body mass index, and diet) were adopted. Three category levels of each metric were added up to a total score ranged 0-14. Logistic regression was performed to explore the association between E2, T, SHBG, and FAI and optimal cardiovascular health (OCH) (score of 11-14). RESULTS: OCH was reached by 153 men (9.3%) and 162 women (10.4%). The prevalence of OCH was higher in the lowest tertile of E2 (38.9%), and of T (43.8%), and the highest tertile of SHBG (48.1%) in women, and the highest tertile of T (43.1%) and SHBG (47.1%) in men. After adjustment for confounders, OCH was associated with lower T (odds ratio and 95% confidence interval, 0.69 [0.48-1.00]) and lower FAI (0.43 [0.32-0.57]) and higher levels of SHBG (4.55 [2.99-6.94]) among women and with higher levels of SHBG (2.56 [1.45-4.49]) in men. CONCLUSIONS: OCH was associated with sex steroids and with SHBG in both men and women. The complexity and temporality of the interrelation between sex steroids, SHBG, and cardiovascular health requires further investigation.

Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis.

IMPORTANCE: In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. DATA SOURCES: Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. STUDY SELECTION: Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. MAIN OUTCOMES AND MEASURES: Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. RESULTS: Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Women's mean global impression of improvement scores indicated minimal improvement to no change. CONCLUSIONS AND RELEVANCE: Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.

Estrogen receptor ß actions in the female cardiovascular system: A systematic review of animal and human studies.

Five medical databases were searched for studies that assessed the role of ERß in the female cardiovascular system and the influence of age and menopause on ERß functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERß signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERß signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERß may be vessel specific and may differ by age and menopause status. ERß seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERß-ligands might contribute to cardiovascular disease prevention.

The global impact of non-communicable diseases on macro-economic productivity: a systematic review.

Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case-control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million US dollars (USD) for COPD to 20.9 billion USD for colon cancer. CHD costs the Australian economy 13.2 billion USD per year. People with DM, COPD and survivors of breast and especially lung cancer are at a higher risk of reduced labor market participation. Overall NCDs generate a large impact on macro-economic productivity in most WHO regions irrespective of continent and income. The absolute global impact in terms of dollars and DALYs remains an elusive challenge due to the wide heterogeneity in the included studies as well as limited information from low- and middle-income countries.

Health in middle-aged and elderly women: A conceptual framework for healthy menopause.

Middle-aged and elderly women constitute a large and growing proportion of the population. The peri and postmenopausal period constitutes a challenging transition time for women's health, and menopausal health is a crucial aspect in healthy and successful aging. Currently, no framework for the concept of healthy menopause exists, despite its recognized importance. Therefore, we aimed to: (i) characterize healthy menopause; (ii) identify aspects that contribute to it; and (iii) explore potential approaches to measure it. We propose healthy menopause as a dynamic state, following the permanent loss of ovarian function, which is characterized by self-perceived satisfactory physical, psychological and social functioning, incorporating disease and disability, allowing the attainment of a woman's desired ability to adapt and capacity to self-manage. The concept of healthy menopause applies to all women from the moment they enter the menopausal transition, up until they reach early and late postmenopause and includes women with spontaneous, iatrogenic, and premature menopause. This conceptualization can be considered as a further step in the maintenance and improvement of health in menopausal women from different perspectives, foremost the woman's own perspective, followed by the clinical, public health, and societal perspectives, and can be seen as a further step in delineating lines for future research. Furthermore, it could facilitate the improvement of adequate preventive and treatment strategies, guide scientific efforts, and aid education and communication to health care practitioners and the general public, allowing women the achievement of their potential and the fulfillment of their fundamental role in society.

The global impact of non-communicable diseases on healthcare spending and national income: a systematic review.

The impact of non-communicable diseases (NCDs) in populations extends beyond ill-health and mortality with large financial consequences. To systematically review and meta-analyze studies evaluating the impact of NCDs (including coronary heart disease, stroke, type 2 diabetes mellitus, cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease and chronic kidney disease) at the macro-economic level: healthcare spending and national income. Medical databases (Medline, Embase and Google Scholar) up to November 6th 2014. For further identification of suitable studies, we searched reference lists of included studies and contacted experts in the field. We included randomized controlled trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and ecological studies carried out in adults assessing the economic consequences of NCDs on healthcare spending and national income without language restrictions. All abstracts and full text selection was done by two independent reviewers. Any disagreements were resolved through consensus or consultation of a third reviewer. Data were extracted by two independent reviewers using a pre-designed data collection form. Studies evaluating the impact of at least one of the selected NCDs on at least one of the following outcome measures: healthcare expenditure, national income, hospital spending, gross domestic product (GDP), gross national product, net national income, adjusted national income, total costs, direct costs, indirect costs, inpatient costs, outpatient costs, per capita healthcare spending, aggregate economic outcome, capital loss in production levels in a country, economic growth, GDP per capita (per capita income), percentage change in GDP, intensive growth, extensive growth, employment, direct governmental expenditure and non-governmental expenditure. From 4,364 references, 153 studies met our inclusion criteria. Most of the studies were focused on healthcare related costs of NCDs. 30 studies reported the economic impact of NCDs on healthcare budgets and 13 on national income. Healthcare expenditure for cardiovascular disease (12-16.5 %) was the highest; other NCDs ranged between 0.7 and 7.4 %. NCD-related health costs vary across the countries, regions, and according to type of NCD. Additionally, there is an increase in costs with increased severity and years lived with the disease. Low- and middle-income (LMI) countries were the focus of just 16 papers, which suggests an information shortage concerning the true economic burden of NCDs in these countries. NCDs pose a significant financial burden on healthcare budgets and nations' welfare, which is likely to increase over time. However further work is required to standardize more consistently the methods available to assess the economic impact of NCDs and to involve (hitherto under-addressed) LMI populations across the globe.

The global impact of non-communicable diseases on households and impoverishment: a systematic review.

The global economic impact of non-communicable diseases (NCDs) on household expenditures and poverty indicators remains less well understood. To conduct a systematic review and meta-analysis of the literature evaluating the global economic impact of six NCDs [including coronary heart disease, stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on households and impoverishment. Medline, Embase and Google Scholar databases were searched from inception to November 6th 2014. To identify additional publications, reference lists of retrieved studies were searched. Randomized controlled trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and ecological studies carried out in adults and assessing the economic consequences of NCDs on households and impoverishment. No language restrictions. All abstract and full text selection was done by two independent reviewers. Data were extracted by two independent reviewers and checked by a third independent reviewer. Studies were included evaluating the impact of at least one of the selected NCDs and on at least one of the following measures: expenditure on medication, transport, co-morbidities, out-of-pocket (OOP) payments or other indirect costs; impoverishment, poverty line and catastrophic spending; household or individual financial cost. From 3,241 references, 64 studies met the inclusion criteria, 75% of which originated from the Americas and Western Pacific WHO region. Breast cancer and DM were the most studied NCDs (42 in total); CKD and COPD were the least represented (five and three studies respectively). OOP payments and financial catastrophe, mostly defined as OOP exceeding a certain proportion of household income, were the most studied outcomes. OOP expenditure as a proportion of family income, ranged between 2 and 158% across the different NCDs and countries. Financial catastrophe due to the selected NCDs was seen in all countries and at all income levels, and occurred in 6-84% of the households depending on the chosen catastrophe threshold. In 16 low- and middle-income countries (LMIC), 6-11% of the total population would be impoverished at a 1.25 US dollar/day poverty line if they would have to purchase lowest price generic diabetes medication. NCDs impose a large and growing global impact on households and impoverishment, in all continents and levels of income. The true extent, however, remains difficult to determine due to the heterogeneity across existing studies in terms of populations studied, outcomes reported and measures employed. The impact that NCDs exert on households and impoverishment is likely to be underestimated since important economic domains, such as coping strategies and the inclusion of marginalized and vulnerable people who do not seek health care due to financial reasons, are overlooked in literature. Given the scarcity of information on specific regions, further research to estimate impact of NCDs on households and impoverishment in LMIC, especially the Middle Eastern, African and Latin American regions is required.