Role of androgens for urethral homeostasis

Background: We observed that patients with hypogonadism are at higher risk to experience artificial urinary sphincter cuff erosion. Sphincter erosions have been found to be associated with urethral atrophy or compromised urethras subsequent to events limiting its blood supply. We therefore analyzed possible mechanisms how a decrease in testosterone serum levels can result decreased urethral blood flow. Methods: In a cohort of >1,200 urethroplasties, tissue specimens obtained during surgeries were analyzed for expression of androgen receptor (AR), AR-responsive TIE-2 associated with angiogenesis, and the endothelial cell marker CD31 for determination of vessel counts were analyzed immunohistochemically. A total of 11 patients were included in whom both tissue and serum testosterone levels within 2 years of the urethroplasty was available. Low serum testosterone level defined as <280 ng/dL. Image J software was used to analyze expression profiles. Results: Mean serum testosterone level was significant lower in hypogonadal patients (179.4 ng/dL) compared to eugonadal patients (375.0 ng/dL, P=0.003). Urethral tissue of hypogonadal patients showed decreased AR expression [1.11% high power field (HPF)] compared to eugonadal patients (1.62%, P=0.016), decreased TIE-2 expression (1.84% HPF vs. 3.08%, P=0.006), and also decreased vessel counts (44.47 vessels/HPF vs. 98.33, P=0.004). There was a direct correlation of AR and TIE-2 expression levels with scrum testosterone levels (rho 0.685, P=0.029, and rho 0.773, P=0.005, respectively). Of note, we did not detect a difference in age, prior radiation, coronary artery disease or hypertension among hypo- or eugonadal patient. However, higher body mass index was associated with low serum testosterone levels. Conclusions: Hypogonadal status is associated with decreased expression of AR and TIE-2 and also reduced vessel count in urethral tissue. We believe that the resulting decreased urethral vascularity subsequent to a hypogonadal state may be an important risk factor for complications of urethral surgery.