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

Background-The increased incidence of coronary artery disease in men compar ed with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effec ts 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 ar tery disease. They underwent measurement of coronary artery diameter and bl ood flow after a 3-minute intracoronary infusion of vehicle control (ethano l) 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 determ ined, and the acetylcholine infusions were repeated. Finally, an intracoron ary bolus of isosorbide dinitrate (1000 mu g) was given. Coronary blood flo w was calculated from measurements of blood flow velocity using intracorona ry Doppler and coronary artery diameter using quantitative coronary angiogr aphy. Testosterone significantly increased coronary artery diameter compare d 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 testosteron e 10(-9) to 10(-7) mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with ba seline (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, respecti vely). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone. Conclusions-Short-term intracoronary administration of testosterone, at phy siological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.