Oxidative stress and inflammation are associated with age-related endothelial dysfunction in men with low testosterone.

CONTEXT Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-age and older (MA/O) men is associated with increased CVD risk. OBJECTIVES We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. DESIGN Cross-sectional. PARTICIPANTS Fifty-eight healthy, non-smoking men categorized as young (N=20; age: 29±4 years, testosterone: 500±58 ng/dL), MA/O with higher testosterone (N=20; age: 60±6 years, testosterone: 512±115 ng/dL), and MA/O lower testosterone (N=18; age 59±8 years, testosterone: 269±48 ng/dL). MAIN OUTCOME MEASURES Brachial artery flow-mediated dilation (FMDBA) measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status [TAS] and oxidized low-density lipoprotein [LDL] cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in MA/O compared to young, regardless of testosterone status (P<0.001). FMDBA was reduced in MA/O lower testosterone (3.7±2.0%) compared to MA/O higher testosterone (5.7±2.2%, p=0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3±1.6%, p=0.022) in MA/O lower testosterone but had no effect in young (P=0.992) or MA/O higher testosterone (P=0.250). FMDBA correlated with serum testosterone (r=0.45, p<0.001), IL-6 (r=-0.41, P=0.002), and CRP (r=-0.28, P=0.041). CONCLUSIONS Healthy MA/O men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.