Abstract

Erectile and endothelial dysfunction are common pathologies of multiple cardiovascular risk factors and are considered longitudinal predictors of cardiovascular events. Oxidative stress and decreases in testosterone levels play an important role in the pathogenesis of endothelial dysfunction. We sought to determine whether the severity of erectile dysfunction (ED) was associated with individual levels of testosterone and oxidative stress, and whether treatment with a phosphodiesterase type 5 inhibitor could reduce oxidative stress and increase testosterone availability. We evaluated the association of salivary 8-hydroxy-2'-deoxyguanosine (8-OHdG), salivary testosterone, International Index of Erectile Function-erectile function domain (IIEF-EF) scores, and Medical Outcome Study (MOS) 36-item Short-Form Healthy Survey (SF-36) questionnaires in 128 middle-aged male volunteers. We investigated the changes in testosterone levels, salivary 8-OHdG levels, IIEF-EF scores, and SF-36 scores in 20 ED patients (according to the IIEF-EF) who took 50 mg of sildenafil once a week for 6 months. IIEF-EF scores were used to assess ED severity. Antioxidant status was defined by salivary 8-OHdG. Salivary testosterone was used to evaluate serum bioavailable testosterone availability. Salivary 8-OHdG (OR = 9.88, 95% CI: 1.52-64.10), salivary testosterone (Odds ratio [OR] = 0.96, 95% CI: 0.93-0.98), and vitality on the SF-36, version 2 (SF-36 v2) (OR = 0.92, 95%CI: 0.84-0.98) were significantly associated with the severity of ED in healthy volunteers. Treatment with sildenafil for 6 months significantly increased the total serum testosterone (426.4 +/- 174.8 vs. 569.6 +/- 146.1 ng/dL, P = 0.021) and salivary testosterone levels (56.1 +/- 22.3 vs. 110.0 +/- 48.4 pg/mL, P < 0.001), whereas it decreased salivary 8-OHdG levels (2.30 +/- 0.23 vs. 0.90 +/- 0.05 ng/mL, P = 0.0046). Salivary 8-OHdG is a useful biomarker for predicting severe ED and hypogonadism in middle-aged men. Once-a-week treatment with sildenafil can have beneficial effects on men's health by decreasing oxidative stress and increasing testosterone levels.

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