Sex-Specific Determinants of Coronary Artery Disease and Atherosclerotic Risk Factors: Estrogen and Beyond

The way we view coronary artery disease in women has changed dramatically over the past decades. From an initial perspective that coronary artery disease was a male disorder and that women were protected by estrogens, there has been the gradual appreciation that this is an equal opportunity disease. Postmenopausal women are more likely than men to be hypertensive, dyslipidemic, and have multiple risk factors. Beyond the appreciation of estrogen's global effects on cardiovascular and metabolic function, our further advances in the understanding of sex-specific risks and management will be based on a greater understanding of the diversity of estrogen-mediated receptor pathways, including appreciation of the sometimes divergent effects of estrogen when acting either via the classic estrogen receptor or the more recently appreciated G protein-coupled estrogen receptor. In addition, the importance of sex-specific regulation of cardiometabolic processes beyond the sex hormones, specifically via SRY regulation, is only beginning to be understood. Finally, the author summarizes his recent studies demonstrating sex-specific G protein-coupled estrogen receptor regulation of blood pressure and cholesterol metabolism that may serve as a paradigm for the elucidation of sex-specific determinants of cardiovascular risk and the basis for sex-specific management of those risks.