EFFECTS OF ANDROGENS ON CORONARY-ARTERY ATHEROSCLEROSIS AND ATHEROSCLEROSIS-RELATED IMPAIRMENT OF VASCULAR RESPONSIVENESS

The factors responsible for the marked gender differences in risk of c oronary heart disease and atherosclerosis severity remain largely unde termined. While some clinical and experimental evidence supports a pro tective effect of endogenous estrogen on the initiation and progressio n of atherosclerosis and incidence of coronary heart disease, much of the epidemiological data do not support this conclusion. The possibili ty that endogenous androgens may have adverse effects on atheroscleros is progression and coronary risk has received little attention. We inv estigated the effects of experimentally induced hyperandrogenism in fe male cynomolgus monkeys with diet-induced atherosclerosis. Animals wer e assigned randomly to one of four treatment groups: (1) untreated con trols, (2) ovariectomized (sex hormone-deficient) controls, (3) treate d with androstenedione and estrone (mild hyperandrogenism), or (4) tre ated with testosterone (male plasma androgen pattern). At necropsy, co ronary atherosclerosis was approximately twice as extensive (P < .05) in testosterone-treated animals relative to untreated controls, while treatment with androstenedione and estrone had no effect on atheroscle rosis extent. Coronary plaque size was positively correlated with lume n size in intact and ovariectomized controls; however, there was no ev idence of a similar relation between animals in either androgen treatm ent group. The atherogenic effects of testosterone were independent of variations in plasma lipoprotein and nonlipoprotein risk variables, A lthough chronic hyperandrogenism had adverse effects on atherosclerosi s progression, it reversed (P < .03) atherosclerosis-related impairmen t of endothelium-dependent vasodilator responses. We conclude that an experimentally induced male plasma androgen pattern results in exacerb ation of diet-induced atherosclerosis and has potentially adverse effe cts on atherosclerosis-related arterial remodeling in female monkeys. The results indicate that testosterone may have a direct role in the i ncreased rate of atherosclerosis progression and increased risk of cor onary heart disease seen in men, relative to women, in most Western so cieties.