Testosterone as a modulator of vascular behavior.
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.
Littleton-Kearney
Marguerite
M
Johns Hopkins Schools of Nursing and Medicine, 525 N. Wolfe Street, Room 460, Baltimore, MD 21205-2110, USA. mkearney@jhmi.edu
Hurn
Patricia D
PD
D000328:Adult; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D013739:Testosterone