Sex Differences In Health Research Articles

Sex differences in health of working population in Russia

Sex differences in health of working population in Russia

Large-scale in silico identification of drugs exerting sex-specific effects in the heart

BackgroundMajor differences exist between men and women in both physiology and pathophysiology. Dissecting the underlying processes and contributing mechanisms of sex differences in health and disease represents a crucial step towards precision medicine. Considering the significant differences between men and women in the response to pharmacotherapies, our aim was to develop an in silico model able to predict sex-specific drug responses in a large-scale.MethodsFor this purpose, we focused on cardiovascular effects because of their high morbidity and mortality. Our model predicted several drugs (including acebutolol and tacrine) with significant differences in the heart between men and women. To validate the sex-specific drug responses identified by our model, acebutolol was selected to lower blood pressure in spontaneous hypertensive rats (SHR), tacrine was used to assess cardiac injury in mice and metformin as control for a non-sex-specific response.ResultsAs our model predicted, acebutolol exhibited a stronger decrease in heart rate and blood pressure in female than male SHRs. Tacrine lowered heart rate in male but not in female mice, induced higher plasma cTNI level and increased cardiac superoxide (DHE staining) generation in female than male mice, indicating stronger cardiac toxicity in female than male mice. To validate our model in humans, we employed two Chinese cohorts, which showed that among patients taking a beta-receptor blocker (metoprolol), women reached significantly lower diastolic blood pressure than men.ConclusionsWe conclude that our in silico model could be translated into clinical practice to predict sex-specific drug responses, thereby contributing towards a more appropriate medical care for both men and women.

Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks

Sex-specific transcriptional and epigenomic profiles are detectable in the embryo very soon after fertilization. I propose that in male (XY) and female (XX) pre-implantation embryos sex chromosomes establish sexually dimorphic interactions with the autosomes, before overt differences become apparent and long before gonadogenesis. Lineage determination restricts expression biases between the sexes, but the epigenetic differences are less constrained and can be perpetuated, accounting for dimorphisms that arise later in life. In this way, sexual identity is registered in the epigenome very early in development. As development progresses, sex-specific regulatory modules are harbored within shared transcriptional networks that delineate common traits. In reviewing this field, I propose that analyzing the mechanisms for sexual dimorphisms at the molecular and biochemical level and incorporating developmental and environmental factors will lead to a greater understanding of sex differences in health and disease. Also see the video abstract here: https://youtu.be/9BPlbrHtkHQ.

Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies.

To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations. One standard deviation increase of TL was associated with 0.021 unit increase (95% confidence interval [CI]: 0.001, 0.042) of standardized mean general cognitive ability. After controlling for sex, the point estimate remained similar (0.019) with a wider CI (95% CI:-0.002, 0.039). The association was attenuated with adjustment for educational attainment (0.009, 95% CI:-0.009, 0.028). No strong evidence was observed for the association of TL and decline in general cognitive ability. Longer TL was associated with higher general cognitive ability levels in the age-adjusted models but not in the models including all covariates, nor with cognitive decline.

Mortal Beings: How Evolution Helps Us Understand Illness and Aging

In these two books, biological anthropologist Richard Bribiescas and developmental psychologist David Geary address sex differences in health and aging from the perspectives of evolutionary biology and psychology. Bribiescas explores the aging process in men and describes why and how men age differently from women, with earlier mortality and greater susceptibility to the diseases of aging. Geary provides a comprehensive survey of the animal and human literature on sex differences in vulnerabilities to the effects of stress on psychological and physical traits. Both authors focus on the role of Darwinian sexual selection as the source of different health outcomes for men and women. These works make valuable contributions to our understanding of why humans get sick and age and argue convincingly for approaching medical research with a greater sensitivity to the role played by biological sex in poor health.

Prohibitin: A new player in immunometabolism and in linking obesity and inflammation with cancer

Immunometabolism, which has important implications in cancer biology, has emerged as a major regulator of different immune cell types. Various factors that integrate metabolic switches within immune cells with signal directed program that promote or inhibit their functions remain largely unidentified. Furthermore, sex differences are known to exist in immune functions and cancer incidences in the body and sex steroid hormones are integral component of these differences. However, factors that mediate such differences, and the potential link between the two fundamental aspects of immune cell biology that contributes to sex differences in health and disease remain unexplored. New evidence derived from novel tissue-specific transgenic mouse models of prohibitin (PHB) has revealed its crucial role in sex differences in adipocyte and macrophage functions and a potential role in endocrine-immune crosstalk. This review provides a point of view on the emerging role of PHB in immune functions with special focus on immunometabolism and on the immunomodulatory effects of sex steroids. We propose that PHB plays a crucial role in integrating cell signaling events with metabolic switches, and may serve as a potential target for cancer immunotherapeutic.

Index to Titles and Authors/Editors of Books Reviewed Volume 92 (2017)

Index to Titles and Authors/Editors of Books Reviewed Volume 92 (2017)

Fetal microchimerism in human brain tumors.

Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively.

Women's and Men's Differing Experiences of Health, Lifestyle, and Aging with Multiple Sclerosis.

The growing population of older people with multiple sclerosis (MS) has led to more interest in understanding factors associated with healthy aging. We aimed to determine whether older women and men with MS have different health and lifestyle behaviors and whether there are sex differences in contributors to perceived health. Data were obtained from a postal survey involving 743 Canadians older than 55 years with MS for at least 20 years. Sex differences in health, lifestyle, mood, and socioeconomics were examined using analysis of variance. Multiple regression was used to build explanatory models of health perception. Despite no differences in age, years with MS, disability, fatigue, or social support, older men (n = 166) experienced lower perceived health and lower resilience and participated less in life roles than older women (n = 577). Men experienced more depressive symptoms, and women reported more anxiety. Depression was the strongest predictor of health perception in both women and men (β = -2.40 and -5.19, respectively, for each 3-point increase in depressive symptoms). Other contributors included household participation, fatigue, resilience, and disability in women and physical activity, financial flexibility, and alcohol use in men. Older men exhibit poorer adaptation to aging with MS than older women.

Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection

Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism that has been proposed to account for this difference is the immunocompetence handicap model, which posits that the greater infectious disease burden in males is due to testosterone, which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors also may contribute to the sex differences in infectious disease burden. Using a murine model of influenza A virus (IAV) infection and a panel of chromosome Y (ChrY) consomic strains on the C57BL/6J background, we present data showing that genetic variation in ChrY influences IAV pathogenesis in males. Specific ChrY variants increase susceptibility to IAV in males and augment pathogenic immune responses in the lung, including activation of proinflammatory IL-17-producing γδ T cells, without affecting viral replication. In addition, susceptibility to IAV segregates independent of copy number variation in multicopy ChrY gene families that influence susceptibility to other immunopathological phenotypes, including survival after infection with coxsackievirus B3. These results demonstrate a critical role for genetic variation in ChrY in regulating susceptibility to infectious disease.

Cellular Mechanisms Driving Sex Differences in Adipose Tissue Biology and Body Shape in Humans and Mouse Models.

Sex differences in adipose tissue distribution and the metabolic, endocrine, and immune functions of different anatomical fat depots have been described, but they are incompletely documented in the literature. It is becoming increasingly clear that adipose depots serve distinct functions in males and females and have specific physiological roles. However, the mechanisms that regulate the size and function of specific adipose tissues in men and women remain poorly understood. New insights from mouse models have advanced our understanding of depot differences in adipose growth and remodeling via the proliferation and differentiation of adipose progenitors that can expand adipocyte number in the tissue or simply replace dysfunctional older and larger adipocytes. A limited ability of a depot to expand or remodel can lead to excessive adipocyte hypertrophy, which is often correlated with metabolic dysfunction. However, the relationship of adipocyte size and function varies by depot and sex. For example, femoral adipose tissues of premenopausal women appear to have a greater capacity for adipose expansion via hyperplasia and hypertrophy; although larger, these gluteal-femoral adipocytes remain insulin sensitive. The microenvironment of specific depots, including the composition of the extracellular matrix and cellular composition, as well as cell-autonomous genetic differences, influences sex- and depot-dependent metabolic and growth properties. Although there are some species differences, studies of the molecular and physiological determinants of sex differences in adipocyte growth and function in humans and rodents are both needed for understanding sex differences in health and disease.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span.

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Review of David C. Geary’s Evolution of Vulnerability: Implications for Sex Differences in Health and Development

Two key questions drive this book: Why are some traits more easily disrupted by stressors than others? Why does the impact of environmental stressors often differ between the sexes? For example, poor nutrition during adolescence disrupts height and physical fitness—but more so in boys than girls. Early Alzheimer’s affects language competencies—but more so in women than men. Not to keep the reader in suspense, Geary announces the answers his questions on page 2: “Traits that have been elaborated through social and sexual selection are especially vulnerable to disruption by environmental and social stressors.” Sexual selection drives these traits to ever greater elaboration, steadily increasing the challenge of pulling them off successfully. Greater upper-body strength makes a male more successful in combat. Peacocks’ elaborate plumage attracts mates despite being detrimental to locomotion and increasing predation risk. But in both cases a cost is associated with their successful expression, and only the best can afford to pay it. These sexually selected traits have an important communicative function. They are honest indicators of gene quality or competitive success. The difficulty of successfully carrying off these handicapping traits makes them especially vulnerable to disruption. And such disruption is valuable to competitors and prospective mates who recognize these disruptions for what they are—clear evidence of a failed bluff. Chapter 2 reviews sexual selection and considers some of the issues that have recently received scrutiny, such as the automatic equation of males with competition Hum Nat (2016) 27:98–103 DOI 10.1007/s12110-015-9249-0

Where There is a Will: Fertility Behavior and Sex Bias in Large Families

This paper argues that the social institutions of lineage maintenance, patrilocality and joint families have a significant role in explaining sex differences in survival and health outcomes in rural India, even when parents do not treat boys and girls differently. Tests using panel data from rural households confirm this explanation, which accounts for 7 percent of excess female mortality in Haryana and Rajasthan and 4 percent in Punjab. An institutional explanation suggests limits on the role for public policy in addressing large sex differences in health and mortality outcomes.

Sex differences in health and mortality in Moscow and Denmark

In high income countries females outlive men, although they generally report worse health, the so-called male-female health-survival paradox. Russia has one of the world's largest sex difference in life expectancy with a male disadvantage of more than 10 years. We compare components of the paradox between Denmark and Moscow by examining sex differences in mortality and several health measures. The Human Mortality Database and the Russian Fertility and Mortality Database were used to examine sex differences in all-cause death rates in Denmark, Russia, and Moscow in 2007-2008. Self-reported health data were obtained from the Study of Middle-Aged Danish Twins (n = 4,314), the Longitudinal Study of Aging Danish Twins (n = 4,731), and the study of Stress, Aging, and Health in Russia (n = 1,800). In both Moscow and Denmark there was a consistent female advantage at ages 55-89 years in survival and a male advantage in self-rated health, physical functioning, and depression symptomatology. Only on cognitive tests males performed similarly to or worse than women. Nevertheless, Muscovite males had more than twice higher mortality at ages 55-69 years compared to Muscovite women, almost double the ratio in Denmark. The present study showed that despite similar directions of sex differences in health and mortality in Moscow and Denmark, the male-female health-survival paradox is very pronounced in Moscow suggesting a stronger sex-specific disconnect between health indicators and mortality among middle-aged and young-old Muscovites.

Where There Is a Will: Fertility Behavior and Sex Bias in Large Families

This paper demonstrates that the social institutions of lineage maintenance, patrilocality, and joint families have a significant role in explaining sex differences in survival and health outcomes in rural India. Tests using panel data from rural households support this explanation, which accounts for 7 percent of excess female mortality in Haryana and Rajasthan and 4 percent in Punjab. An institutional explanation suggests limits on the role for public policy in addressing large sex differences in health and mortality outcomes.

Where There Is a Will

Abstract This paper demonstrates that the social institutions of lineage maintenance, patrilocality, and joint families have a significant role in explaining sex differences in survival and health outcomes in rural India. Tests using panel data from rural households support this explanation, which accounts for 7 percent of excess female mortality in Haryana and Rajasthan and 4 percent in Punjab. An institutional explanation suggests limits on the role for public policy in addressing large sex differences in health and mortality outcomes.

Why research sex differences and similarities?

Why research sex differences and similarities?

An emerging role for microRNAs in sexually dimorphic neurobiological systems

Over the past 20years, our understanding of the basic mechanisms of gene regulation has vastly expanded due to the unexpected roles of small regulatory RNAs, in particular microRNAs (miRNAs). miRNAs add another layer of complexity to the regulation of effector molecules for nearly every physiological process, making them excellent candidate molecules as therapeutic targets, biomarkers, and disease predictors. Hormonal contributions to mature miRNA expression, biosynthetic processing, and downstream functions have only just begun to be investigated. Elucidating the physiological consequences of miRNA sexual dimorphism, and their associated regulatory processes, may be key toward understanding both normal and pathological processes in the brain. This short review provides a basic overview of miRNA biosynthesis, their role in normal brain development, and potential links to neurological diseases. We conclude with a brief discussion of the current knowledge of sex-specific miRNA processes in both the brain and the heart to conceptually integrate the relevance of miRNAs with the overarching theme ("sex differences in health and disease: brain and heart connections") of this special topics issue.

Sex inequalities in physical and mental functioning of British, Finnish, and Japanese civil servants: Role of job demand, control and work hours

In general, women report more physical and mental symptoms than men. International comparisons of countries with different welfare state regimes may provide further understanding of the social determinants of sex inequalities in health. This study aims to evaluate (1) whether there are sex inequalities in health functioning as measured by the Short Form 36 (SF-36), and (2) whether work characteristics contribute to the sex inequalities in health among employees from Britain, Finland, and Japan, representing liberal, social democratic, and conservative welfare state regimes, respectively. The participants were 7340 (5122 men and 2218 women) British employees, 2297 (1638 men and 659 women) Japanese employees, and 8164 (1649 men and 6515 women) Finnish employees. All the participants were civil servants aged 40–60 years. We found that more women than men tended to have disadvantaged work characteristics (i.e. low employment grade, low job control, high job demands, and long work hours) but such sex differences were relatively smaller among employees from Finland, where more gender equal policies exist than Britain and Japan. The age-adjusted odds ratio (OR) of women for poor physical functioning was the largest for British women (OR = 2.08), followed by for Japanese women (OR = 1.72), and then for Finnish women (OR = 1.51). The age-adjusted OR of women for poor mental functioning was the largest for Japanese women (OR = 1.91), followed by for British women (OR = 1.45), and then for Finnish women (OR = 1.07). Thus, sex differences in physical and mental health was the smallest in the Finnish population. The larger the sex differences in work characteristics, the larger the sex differences in health and the reduction in the sex differences in health after adjustment for work characteristics. These results suggest that egalitarian and gender equal policies may contribute to smaller sex differences in health, through smaller differences in disadvantaged work characteristics between men and women.