Sex and Sex Hormone–Dependent Cardiovascular Stress Responses

Abstract

Different stimuli confer mechanical and hormonal stress to the heart. Pressure overload (PO) affects the myocardium, kidney, and peripheral fat. The latter may be considered simultaneously as a novel end organ and as a mediator in cardiovascular damage and, by its interplay with the heart, contributes to the development of pathological myocardial hypertrophy (MH). In contrast to pathological MH, in physiological MH the heart serves as an end organ for recurrent pressure spikes without the development of pathology. Complex stressors such as mineralocorticoid excess and salt challenge induce complex pathological cardiac and renal phenotypes. Understanding the underlying sex-specific mechanisms mediating these processes may help to design new therapeutic strategies. The major goal of this review is to analyze sex differences in physiological and pathological forms of cardiovascular stress and its effects on different organs, including the heart, kidney, and peripheral fat. Exercise-induced physiological MH differs markedly from pathological MH resulting from hypertension, valve disease, or other challenges. Physiological MH is reversible, associated with improved cardiac function and lack of fibrosis.1 At the level of cardiac metabolism, MH during the course of physical training is accompanied by enhanced fatty acid oxidation and reduced glucose use. ### Clinical Impact and Relevance in Humans Studies in humans comparing exercise-mediated MH in both sexes are limited. Left ventricular mass (LVM) is significantly increased in male endurance athletes by 36±14% compared with untrained control subjects.2 In young adult elite athletes, both sexes exhibited similar increases in LVM and LVM indices when compared with their sex-matched sedentary controls.3 However, limitations of these studies in humans have to be taken into account: despite a comparable training duration (hours/week and years at elite level) in female and male athletes, no detailed information about training intensity was provided.3 Putative sex differences in training intensity might have influenced exercise-induced cardiac remodeling. A lower …