H igh androgen levels in men have been regarded as a risk factor for coronary artery disease (CAD). However, it has recently been demonstrated that supplements of androgens inhibit atheroma formation in castrated male animals, suggesting that testosterone may be antiatherosclerotic. In men with angina pectoris, a significant inverse correlation was found between plasma testosterone levels and the extent of CAD, demonstrating that low testosterone levels could be a risk factor for CAD. Other reports suggest that testosterone replacement therapy in men with CAD has a beneficial effect on angina pectoris and exercise-induced ST-segment depression. Another study showed that testosterone enhanced endotheliumindependent coronary artery dilation and flow-mediated brachial arterial vasoreactivity in men with CAD. In this study, we assessed the effects of oral testosterone administration on brachial arterial vasoreactivity in men with CAD. • • • Thirty-five men (aged 58 8 years) with CAD were randomized to placebo (n 17) or treatment group (n 18). Demographics of the study group are summarized in Table 1. Diagnostic criteria of CAD are a history of unstable and stable angina pectoris with angiographic evidence ( 50% stenosis of lumen diameter). Exclusion criteria were inflammatory disease or malignancy, ejection fraction 45%, clinical evidence of heart failure, and Q-wave myocardial infarction within 3 months before the study. The treatment group completed oral administration of 160 mg of testosterone undecanoate (Andriol, N.V. Organon, Oss, The Netherlands) daily for 4 weeks followed by 80 mg testosterone undecanoate for 8 weeks, in addition to their current medication. Using high-resolution ultrasound, we assessed brachial arterial vasoreactivity to reactive hyperemia (flow-mediated dilation) and sublingual nitroglycerin (nitroglycerin-mediated dilation) at baseline and after 12 weeks of treatment. Patients taking nitrates discontinued therapy 24 hours before the study to avoid nitrate tolerance. A 10-MHz linear phased-array ultrasound transducer (GE Vigmed Ultrasound, Horten, Norway) was used to image the dominant arm brachial artery longitudinally 3 to 5 cm just above the antecubital fossa. All patients rested in the supine position for 10 minutes in a quiet room. After the depth and gain setting were optimized to identify the vessel wall, the brachial artery diameter was measured from the anterior to the posterior interface between the media and the adventitia and determined at end-diastole on B mode. Reactive hyperemia was induced by inflation and then deflation of a pneumatic cuff placed around the upper arm. The blood pressure cuff was inflated to 250 mm Hg for 5 minutes. After release of the cuff, brachial artery diameter was measured within the first 15 seconds of reactive hyperemia. The brachial artery was allowed to return to the baseline level until 10 minutes after cuff release. Then, a further baseline brachial artery diameter was obtained. Nitroglycerin, 0.6 mg, was then given sublingually, and the brachial artery diameter was measured for the ensuing 3 minutes. The percent change in diameter caused by reactive hyperemia was calculated by dividing the difference from baseline end-diastolic diameter by the baseline value. The percent change in diameter caused by nitroglycerin administration was also calculated in the same way. Blood pressure and heart rate were measured before the examination. All data were calculated as an average of 4 consecutive cardiac cycles. Early morning blood sampling for fasting lipid profiles was performed and plasma-free testosterone levels were obtained immediately before ultrasound imaging and 12 weeks later. A standard radioimmunoassay method was used for analysis (DSL-4900 kit, Diagnostic System Laboratory Inc., Houston, Texas). All descriptive data are presented as mean SD and analyzed using SPSS for Windows 9.0 (SPSS Inc., Chicago, Illinois) From the Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute, College of Medicine, Seoul; and Department of Food and Nutrition, College of Ecology, Yonsei University, Seoul, South Korea. Dr. Jang’s address is: Cardiology Division, Yonsei Cardiovascular Center, Yonsei University College of Medicine, 134, Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, South Korea. E-mail: jangys1212@yumc.yonsei.ac.kr. Manuscript received August 10, 2001; revised manuscript received and accepted December 10, 2001. TABLE 1 Clinical Characteristics of Study Group