Low Testosterone Levels Result in Decreased Periurethral Vascularity via an Androgen Receptor-mediated Process: Pilot Study in Urethral Stricture Tissue.

ABSTRACT

OBJECTIVE: To compare expression of androgen receptor (AR) and angiopoietin 1 receptor TIE-2 and vessel density of urethral stricture tissue among eugonadal and hypogonadal men to identify a pathophysiological basis for our observations that low testosterone is associated with urethral atrophy. METHODS: Among 1200 men having urethroplasty at our institution, we retrospectively identified 11 patients with testosterone levels drawn within 2 years of surgery. Low testosterone was defined as <280 ng/dL and detected in 5 of 11 (45.5%) patients. Urethral tissue samples were analyzed using immunohistochemistry for AR, TIE-2 (a downstream target of activated AR linking it to angiogenesis), and CD31 expression. RESULTS: Mean testosterone was 179.4 ng/dL for patients classified as having low testosterone and 375.0 ng/dL for controls (P = .003). We found a significant decrease of AR expression (1.11%high power field [HPF] vs 1.62, P = .016), TIE-2 expression (1.84%HPF vs 3.08, P = .006), and vessel counts (44.47 vessels/HPF vs 98.33, P = .004) in men with low testosterone. Expression levels of AR and TIE-2 were directly correlated to testosterone levels (rho 0.685, P = .029, and rho 0.773, P = .005, respectively). We did not find a difference in age, radiation, or comorbidities among patients with normal or low testosterone levels, with the exception of higher body mass index in the latter. CONCLUSION: Men with low testosterone levels demonstrate decreased AR and TIE-2 expression and lower vessel counts in periurethral tissue samples of urethral strictures. Our results provide a rationale for a mechanistic relationship between low testosterone levels and decreased periurethral vascularity that may contribute to urethral atrophy in patients with urethral strictures.