Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution

The effect of testosterone (T) substitution therapy on blood vessel functions in relation to cardiovascular disease has not been fully elucidated. In 36 newly diagnosed nonsmoking hypogonadal men (37.5 +/- 12.7 yr) endothelium-dependent flow-mediated vasodilatation (FMD; decreased in atherosclerosis) of the brachial artery was assessed before treatment and after 3 months of T substitution therapy (250 mg testosterone enanthate im every 2 wk in 19 men, human chorionic gonadotropin sc twice per week in 17 men). Twenty nonsmoking controls matched for age, low-density lipoprotein cholesterol (LDL-C), body height, and baseline diameter of the artery were selected for repeated measurements from a larger eugonadal control group (n = 113). In hypogonadal men, basal FMD (17.9 +/- 4.5%) was significantly higher than in the large (11.9 +/- 6.4%) and matched control (11.8 +/- 7.1%, both P < 0.001) groups. Grouped multiple linear regression analysis revealed a significant negative association of T levels with FMD within the hypogonadal range, but no significant association was seen within the eugonadal range. During substitution therapy, T levels increased from 5.8 +/- 2.3 to 17.2 +/- 5.1 nmol/liter and FMD decreased significantly to 8.6 +/- 3.1% (P < 0.001, analysis for covariance for repeated measurements including matched controls). LDL-C and advanced age contributed significantly to decrease FMD (P = 0.01, P = 0.04, respectively). Because T substitution adversely affects this important predictor of atherosclerosis, other contributing factors (such as smoking, high blood glucose, and LDL-C) should be eliminated or strictly controlled during treatment of hypogonadal men.