The effect of androgen status on the structural and functional success of cavernous nerve grafting in an experimental rat model

Abstract

Purpose: Iatrogenic erectile dysfunction following radical prostatectomy is primarily neurogenic in origin. Attempts to improve postoperative potency aim to preserve or regenerate the autonomic cavernous nerves. Testosterone is integral for erectile function and it has profound positive effects on nerve regeneration. Androgen ablation impairs nerve regeneration. In this animal study we evaluated whether testosterone deprivation effects axonal regeneration in cavernous nerve grafts or the erectile response to cavernous nerve graft stimulation.

Materials and methods: A total of 45 male Sprague-Dawley rats underwent bilateral cavernous nerve neurotomy, followed by unilateral nerve graft using the genitofemoral nerve. Rats were then randomized to castrate, intact and testosterone treated arms. At 3 months grafts were explored and electrostimulation was performed with intracavernous pressure responses recorded. Grafted nerves were then harvested for immunohistochemical analysis.

Results: Univariate analysis demonstrated a significant difference in the maximal intracavernous pressure response between groups. Mean +/- SEM maximal intracavernous pressure was 47 +/- 7.9, 23.7 +/- 4.9 and 59 +/- 7.4 mm Hg in the intact, castrate and testosterone treated groups, respectively (p = 0.003). Total axon counts did not differ between treatment groups with a mean total axon count of 789 +/- 97, 706 +/- 134 and 726 +/- 111, respectively. Castrate animals had lower neuronal nitric oxide synthase axon counts compared to intact animals (p = 0.089). The mean axon count was 480 +/- 78, 285 +/- 53 and 435 +/- 71 in the intact, castrate and testosterone treated groups respectively.

Conclusions: Castration resulted in a decreased erectile response to electrostimulation following nerve grafting. This may be due to decreased graft neuronal nitric oxide synthase positive axonal regeneration. This has important implications in patients in whom cavernous nerve grafting could be considered.