Erectile Dysfunction Secondary to Nerve-sparing Radical Retropubic Pro statecto my: Co mparative Phosphodiesterase-5 Inhibitor Efficacy for Therapy and Novel Preventio n Strategies Harin Padma-Nathan, MD*, Andrew McCullough, MD, and Christopher Forest, PA-C Address * Male C linic, 9100 W ilshire Blvd., Suite 360, East Tower, Beverly H ills, CA 90210, USA. E-mail: hpn@ insyght.com Current Urology Reports 2004, 5: 467–471 Current Science Inc. ISSN 1527-2737 Copyright © 2004 by Current Science Inc. Introduction Erectile dysfunction following radical prostatectomy is immediate, with profound effects on nocturnal, morning, and psychogenic erections [1••,2,3]. The etiology of the immediate loss of nocturnal activity, although debated by experts in the past, appears to be the result of intraoperative neuropraxia with subsequent apoptosis [4–8]. There is little evidence of arterial injury during radical prostatectomy [9]. Over time, there appears to be recovery of nocturnal activity that corresponds with an increase in natural erectile function [1••]. The recovery of erectile function indeed is slow, requir- ing up to 18 to 24 months. This is consistent with a slowly reso lving neuro praxia [7,8,10]. Discussion Most patients treated for post-radical retropubic prostatec- tomy (RRP)-related erectile dysfunction are treated with phosphodiesterase-5 (PDE-5) inhibitors; therefore, this review will focus on this class of oral agents. As neuro- praxia resolves, the trabecular smooth muscle becomes increasingly responsive to sildenafil, as one might expect, because the mechanism of sildenafil and the other PDE-5 inhibitors is dependent on the production of nitric oxide from the nerve endings. However, success with a PDE-5 inhibitor in the first 6 months can be expected to be very low. With increasingly accurate predictors of localized dis- ease, most patients will know with some degree of cer- tainty before the surgery whether they will have a bilateral, unilateral, or nonsparing procedure [12,13]. Patients assume that bilateral nerve-sparing is synonymous with preservation of potency, not realizing that few men are as good postoperatively as they were preoperatively, and the term “potent” is increasingly defined in terms of response to sildenafil [10]. In a nonrandomized, nonconsecutive, highly selected population of 91 men taking sildenafil after RRP, Zippe et al. [14] reported a 72% (38/53) rate of erections satisfac- Postprostatectomy erectile dysfunction appears to be initi- ated by neuropraxia and perpetuated by cavernosal smooth muscle apoptosis. Phosphodiesterase-5 (PD E-5) inhibitor therapy is the current cornerstone of erectile dysfunction (ED ) therapy in this population. Although no head-to-head trials have been performed with sildenafil, vardenafil, and tad- alafil in this population, there are numerous studies in the general ED population. The results of these studies demon- strate that neither of the new PD E-5 inhibitors met statistical noninferiority to sildenafil. Sildenafil has been studied in a novel primar y prevention modality using nightly administra- tion after a bilateral ner ve-sparing prostatectomy. In this novel approach, it effected a sevenfold improvement in return of spontaneous, normal erectile function 2 months after drug discontinuation. This effect appears to be medi- ated by proper ties unique to sildenafil that include improved endothelial function and neuronal regeneration and neuro- protection. In primar y prevention, unlike ED therapy, one has only “one shot” by definition. Therefore, it is even more critical to apply evidence-based medicine.