Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease.

Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions.

Gender-specific medicine in the genomic era.

This article is intended to illuminate several important changes in our concept of gender-specific medicine in the genomic era. It reviews the history of gender-specific medicine, pointing out the changes in our perception of the nature of biological sex and our expanding knowledge of how it affects the phenotype. The old debate about 'nature versus nurture' is now largely resolved; the two are inextricably intertwined as a result of epigenomic regulation of gene expression; many of the resulting phenotypic changes are inherited and affect future generations. More accurate, rapid and cheaper methods of editing genomic composition are implementing a more sophisticated understanding of how genes function and how individual components of the genome might be added or eliminated to maintain health and prevent disease. As Venter predicted, the new discipline of synthetic biology, based on the creation and use of novel 'designer' chromosomes is an inevitable expansion of our ability to decipher the naturally occurring genome and the factors that control its expression. As we move with unexpected and stunning rapidity into our exploration and manipulation of the genetic code, our investigations must acknowledge the solidly established fact that biological sex will have a profound impact on the interventions we have made and will make in the future. Unfortunately, in spite of the recent urging of the National Institutes of Health (NIH) that sex be included as an essential variable in all levels of scientific investigation, genuine issues remain to be resolved before all scientists accept not only the importance of doing this, but also how to implement it.

Gender-specific care of the patient with diabetes: review and recommendations.

BACKGROUND: Men and women differ in their experience of diabetes mellitus (DM). For optimal prevention and treatment of the disease, these differences must be acknowledged. Unfortunately, most studies of diabetes have focused almost exclusively on men. OBJECTIVE: The purpose of this review was to survey the literature about the sex-specific features of DM and to make recommendations for the gender-specific care of patients. METHODS: An initial literature search was performed with Google Scholar and MEDLINE (1995-2005) using the search terms sex/gender, women, diabetes mellitus, and coronary artery disease, and specific topic headings such as polycystic ovary syndrome. The bibliographies of articles were used extensively to augment the search, and more specific search terms were included. The strength of each recommendation was assessed. RESULTS: : Even when women were included in clinical trials, investigators typically made no attempt to assess the impact of sex differences on the reported results. Existing studies, however, reveal several differences between men and women with diabetes. The prevalence of DM is growing fastest for older minority women. Women with diabetes, regardless of menopausal status, have a 4- to 6-fold increase in the risk of developing coronary artery disease (CAD), whereas men with diabetes have a 2- to 3-fold increase in risk. Women with diabetes have a poorer prognosis after myocardial infarction and a higher risk of death overall from cardiovascular disease than do men with diabetes. Women with type 2 DM experience more symptoms of hyperglycemia than do their male counterparts. Obesity, an important contributor to type 2 DM, is more prevalent in women. Women with diabetes have an increased risk of hypertension compared with men with diabetes. Women have a more severe type of dyslipidemia than do men (low levels of high-density lipoprotein cholesterol, small particle size of low-density lipoprotein cholesterol, and high levels of triglycerides), and these risk factors for CAD have a stronger influence in women. Oxidative stress may confer a greater increase in the risk of CAD for women with diabetes than for men with diabetes. Many other sex differences in DM are due to women's reproductive physiology. Polycystic ovary syndrome is an important correlate of insulin resistance and the metabolic syndrome. Gestational diabetes mellitus (GDM) increases the risk of cardiovascular disease and type 2 DM. Women are less likely than men to receive aggressive treatment for CAD and to achieve treatment goals. Critical recommendations for women include exercise, testing for CAD, daily aspirin to counteract the prothrombotic state, depression screening, careful treatment to avoid weight gain, long-term follow-up of children of women with GDM, control of risk factors for CAD, and aggressive treatment with coronary angioplasty for CAD. Disease management programs for patients with diabetes have been shown to save money and improve outcomes, and should continue to incorporate information about sex-specific differences in DM as it becomes available. CONCLUSION: Gender-specific care of the patient with diabetes should be informed by evidence-based recommendations.

Integrating topics of sex and gender into medical curricula-lessons from the international community.

In the era of individualized medicine, training future scientists and health-care providers in the principles of sex- and gender-based differences in health and disease is critical in order to optimize patient care. International successes to incorporate these concepts into medical curricula can provide a template for others to follow. Methodologies and resources are provided that can be adopted and adapted to specific needs of other institutions and learning situations.

Beyond women's health the new discipline of gender-specific medicine.

At its best, women's health is not something to be developed as an isolated discipline. If instead biologic sex is used as an important variable in research protocols, studying and comparing men and women directly, the data prompt the formulation of questions that never otherwise would be asked. In answering those questions, one can fashion more accurate and complete models not only of human physiology, but also of the pathophysiology of disease.

The changing position of women in the medical marketplace: women's health morphs into gender-specific medicine.

Traditionally, society--including the academic medical community--has concentrated on the male patient. Women were protected from clinical investigation on human subjects. However, World War II brought about far-reaching changes. The experience of Americans during the prolonged struggle gave them an enduring confidence in the power of science to prolong and improve human life that culminated in the expansion of the National Institutes of Health under the leadership of James A. Shannon. The other profound change in American society was in the attitude of women, who, as a result of their enormously increased options during the war to hold jobs and enter professions that had previously been the exclusive province of men, united in the feminist movement. By the end of the 1980s, the voices of women themselves galvanized the United States government to effect a series of maneuvers that have revolutionized our concept of the importance of biological sex in human biology. This paper reviews the changes in American medical research, and the delivery of medical care, to men and women over the past century, which laid the foundation for an in-depth exploration of the impact of gender on normal human function and the way human beings experience disease.