Male sex is an acknowledged risk factor for many forms of cardiovascular disease, and vascular disease prevalence patterns appear to be different in men versus women. The vascular properties of the principal mammalian androgen, testosterone, are complex and linked to dose, duration of exposure, presence of underlying vascular disease, and, possibly, biological sex. Data from isolated vessels and animal models suggest that pharmacological doses of testosterone, or its
potent intracellular metabolite dihydrotestosterone, produce vasodilation. Testosterone?s major effect on vascular beds at physiologic concentrations
remains unclear, with documentation of both vasodilatory and vasoconstrictive actions. Results of various studies suggest that testosterone can alter vascular tone through both endothelium-dependent
and endothelium-independent mechanisms in a variety of vascular beds and vessel types. Testosterone?s endothelium-dependent effects are likely mediated at least in part through nitric oxide (NO) elaboration, whereas mechanisms of endothelium-independent effects involve 1 or more types of smooth muscle ion conductance channels. Data from clinical studies indicate that, in men, androgen replacement may provide beneficial effects when coronary artery disease is present. Conversely, in women, testosterone may augment existing hypertension, increase risk for cardiovascular events, or promote atherogenesis. However, it should be emphasized that most of these observations are anecdotal or come from small-scale clinical studies, and limited information is available in
women. New research is required to understand the potential efficacy of androgen therapy, or lack thereof. This review focuses on current understanding of testosterone?s physiological effects on vascular behavior and of testosterone?s putative role in vascular health and disease. |