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LOW TESTOSTERONE LEVELS PREDISPOSE TO URETHRAL ATROPHY DUE TO DECREASED URETHRAL VASCULARITY VIA AN ANDROGEN RECEPTOR-MEDIATED PROCESS

Login to Access Video or Poster Abstract: MP36-03
Sources of Funding: None

Introduction

We recently identified that hypogonadism predisposes to artificial urinary sphincter (AUS) erosion. The aim of this study was to compare histologic features of human periurethral tissue among eugonadal and hypogonadal patients in order to identify pathologic mechanisms for this predisposition.

Methods

Among a cohort of over 1200 men having urethroplasty at our institution, we retrospectively identified 11 patients who had serum testosterone levels drawn within 2 years of surgery and who had tissue samples available. Low serum testosterone was defined as <280 ng/dl. Tissue samples were analyzed by immunohistochemistry to determine expression of androgen receptor (AR), TIE-2 (a downstream target of activated AR linking it to angiogenesis), and CD31 (to highlight vessels). Microscopic images were objectively evaluated for protein expression and vessel counts using Image J software.

Results

We found a significant decrease of AR expression (1.11%HPF vs. 1.62, p=0.016), TIE-2 expression (1.84%HPF vs. 3.08, p=0.006), and vessel counts (44.47 vessels/HPF vs. 98.33, p=0.004) in men with low serum testosterone. Expression levels of AR and TIE-2 were directly correlated to serum testosterone levels (rho 0.685, p=0.029, and rho 0.773, p=0.005, respectively). We did not find a difference in age, prior radiation, co-morbidities such as coronary artery disease or hypertension among patients with normal or low testosterone levels with the exception of higher body mass index in patients with low testosterone levels.

Conclusions

Men with low serum testosterone levels demonstrate decreased expression of AR and TIE-2 and lower vessel count in periurethral tissues. Our results provide a rationale for a mechanistic relationship between low testosterone levels and subsequent decreased periurethral vascularity. We believe that this results in urethral atrophy conferring a higher risk of AUS erosion.

Funding

None

Authors
Matthias D Hofer
Payal Kapur
Billy H Cordon
Farrah Hamoun
David Russell
Jeremy M Scott
Claus G Roehrborn
Allen F Morey
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