Testosterone and Atherosclerosis Progression in Men

There is a widespread perception that the gender differences in the prevalence of coronary artery disease (CAD) are due to higher testosterone concentrations in men and that testosterone supplementation in men would adversely affect the plasma lipoprotein profile, therefore increasing the risk of atherosclerotic heart disease. The case reports of cardiovascular accidents among athletes who had abused androgenic steroids have strengthened this notion; however, there are no data substantiating a cause-and-effect relationship between androgens and cardiovascular disease. The manuscript by Fukui et al. (1) in this issue of Diabetes Care adds to a growing body of epidemiological data demonstrating that low testosterone concentrations in men are associated with a higher risk of CAD.

Since there are currently no intervention studies of the effects of long-term testosterone administration on CAD, inferences about the risks of testosterone administration have been derived from studies assessing the effect of testosterone on lipoprotein metabolism, markers of inflammation, and insulin sensitivity. The effects of androgen supplementation on plasma lipids depend on the dose, the route of administration (oral or parenteral), the type of androgen (aromatizable or not), and the subject population (whether young or old and hypogonadal or not). While supraphysiological doses of testosterone and nonaromatizable androgens undoubtedly decrease plasma HDL cholesterol levels (2–4), physiologic testosterone replacement in older men has been associated with only a modest or no decrease in plasma HDL cholesterol (5,6). Cross-sectional studies of middle-aged men (7) find a direct, rather than inverse, relationship between serum testosterone levels and plasma HDL cholesterol concentrations. It has also been suggested that the decrease in HDL cholesterol with testosterone administration might be the …