Miller, Virginia M.

Sex refers to biological differences between men and women. Although sex is a fundamental aspect of human physiology that splits the population in two approximately equal halves, this essential biological variable is rarely considered in the design of basic physiological studies, in translating findings from basic science to clinical research, or in developing personalized medical strategies. Contrary to sex, gender refers to social and cultural factors related to being a man or a woman in a particular historical and cultural context. Unfortunately, gender is often used incorrectly by scientists and clinical investigators as synonymous with sex. This article clarifies the definition of sex and gender and reviews evidence showing how sex and gender interact with each other to influence etiology, presentation of disease, and treatment outcomes. In addition, strategies to improve the inclusion of female and male human beings in preclinical and clinical studies will be presented, and the importance of embedding concepts of sex and gender into postgraduate and medical curricula will be discussed. Also, provided is a list of resources for educators. In the history of medical concepts, physiologists have provided pivotal contributions to understanding health and disease processes. In the future, physiologists should provide the evidence for advancing personalized medicine and for reducing sex and gender disparities in health care.

ObjectiveIt is unclear why despite a comparable cardiometabolic risk profile, “metabolically benign” overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals.Design and MethodsIn cross‐sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at‐risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined “metabolically benign” with ≤ 1, and “at‐risk” with ≥2 components of the metabolic syndrome.ResultsCompared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04‐2.99), hepatic fat (OR: 1.90, 95% CI:1.12‐3.24) and leptin (OR: 2.15, 95% CI: 1.23‐3.76), and the bottom tertile of HMW‐adiponectin (OR: 2.90, 95% CI: 1.62‐5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22‐8.29), pericardial fat (OR: 9.27, 95% CI: 5.52‐15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77‐4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60‐3.94).ConclusionsLevels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.

Sex, a biological variable, and gender, a cultural variable, define the individual and affect all aspects of disease prevention, development, diagnosis, progression, and treatment. Sex and gender are essential elements of individualized medicine. However, medical education rarely considers such topics beyond the physiology of reproduction. To reduce health care disparities and to provide optimal, cost-effective medical care for individuals, concepts of sex and gender health need to become embedded into education and training of health professionals. In September 2012, Mayo Clinic hosted a 2-day workshop bringing together leading experts from 13 U.S. schools of medicine and schools of public health, Health Resources and Services Administration Office of Women's Health (HRSA OWH), the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH), and the Canadian Institute of Health and Gender. The purpose of this workshop was to articulate the need to integrate sex- and gender-based content into medical education and training, to identify gaps in current medical curricula, to consider strategies to embed concepts of sex and gender health into health professional curricula, and to identify existing resources to facilitate and implement change. This report summarizes these proceedings, recommendations, and action items from the workshop.