Androgen Deprivation Is Associated With Enhanced Endothelium-Dependent Dilatation in Adult Men

Male gender is an independent risk factor for coronary artery disease, and androgen administration has been associated with increased atherosclerosis in experimental animals. Since endothelial dysfunction is an important event in the atherogenic process, we hypothesized that androgen deprivation in adult men might be associated with enhanced arterial endothelial function. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilatation) and after nitroglycerin (an endothelium-independent dilator). We studied 30 adult males aged 40 to 70 years: 10 had had bilateral orchidectomy and/or maximal androgen blockade for ≥6 months for treatment of prostate cancer, and all were in complete remission (group 1). Ten healthy controls (group 2) and 10 controls who had remission from nonprostate cancers (group 3) were matched for age and smoking history. Testosterone levels were lower in men in group 1 versus groups 2 or 3 (0.8±0.1 versus 19.2±8.4 or 16.1±4.9 nmol/L,P <.001). By contrast, endothelium-dependent dilatation was markedly higher in group 1 than in groups 2 or 3 (6.2±3 versus 2.7±2 or 2.0±1.9%,P <.001). The nitroglycerin response was similar in all three groups (P =.92). On multivariate analysis, increased endothelium-dependent dilatation was significantly associated with low serum testosterone levels (P =.001) but not with cholesterol levels or with a past history of malignancy (P >.25). The withdrawal of male sex hormones may be associated with enhanced endothelial function in adult men. This is consistent with a deleterious effect of physiologic levels of male sex steroids on the arterial wall.