Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease

Background-The increased incidence of coronary artery disease in men compared with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effects on coronary arteries in animals, as shown both in vitro and in vivo. The effect of testosterone on the human coronary circulation remains unknown. Methods and Results-We studied 13 men (aged 61+/-11 years) with coronary artery disease. They underwent measurement of coronary artery diameter and blood flow after a 3-minute intracoronary infusion of vehicle control (ethanol) followed by 2-minute intracoronary infusions of acetylcholine (10(-7) +/- to 10(-5) mol/L) until peak velocity response. A dose-response curve to 3-minute infusions of testosterone (10(-10) to 10(-7) mol/L) was then determined, and the acetylcholine infusions were repeated. Finally, an intracoronary bolus of isosorbide dinitrate (1000 mu g) was given. Coronary blood flow was calculated from measurements of blood flow velocity using intracoronary Doppler and coronary artery diameter using quantitative coronary angiography. Testosterone significantly increased coronary artery diameter compared with baseline (2.78+/-0.74 mm versus 2.86+/-0.72 mm [P=0.05], 2.87+/-0.71 mm [P=0.038], and 2.90+/-0.75 mm [P=0.005] for baseline versus testosterone 10(-9) to 10(-7) mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with baseline (geometric mean [95% CI]: 32 [25, 42] versus 36.3 [27, 48] {P=0.006}, 35.3 [26, 47] {P-0.029} 36.8 [28, 49] {P=0.002}, and 37 [28, 48] {P=0.002} mL/min for baseline versus testosterone 10(-10) to 10(-7) mol/L, respectively). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone. Conclusions-Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.