The three major definitive treatments for prostate cancer, radical prostatectomy (RP), pelvic radiation (RT) and androgen deprivation (AD) in animal and human models have been shown to impair erectile function. The consequences of erectile dysfunction (ED) include spiraling sexual confidence with subsequent loss of self-esteem and potentially relationship discord. The major mechanisms at play in radical pelvic surgery and pelvic radiation induced ED are the same although the three major mechanisms are weighted differently and thes einclude neural injury, artery injury (endothelial dysfunction) and cavernosal smooth muscle damage). Neural injury, likely the major factor for the surgical patient occurs at the time of neurovascular bundle dissection and even in the most experienced surgical hands translates into significant impairment of erectile function in at least the early stages after surgery. The impact of radiation on neural function has not been not well measured. We know from clinical practice that most men respond to PDE5 inhibitors (PDE5i) at least within the first 2 years after radiation completion, thus whatever effect radiation has on the cavernous nerves is either minimal or delayed. The consequences of neural injury include structural changes in the cavernosal smooth muscle (apoptosis, upregulation of fibrogenic cytokines, collagenization) and endothelium. Thus, even neuropraxia may lead to erectile tissue damage with a long-term negative impact on erectile function recovery. It is well appreciated that cavernosal smooth muscle damage is associated with the development of venous leak, which portends a poor prognosis for the recovery of either spontaneous or PDE5i-induced erections. The impact of RT on arterial integrity is well known as the endarteritis obliterans that is occurs leads to significant cavernosal artery insufficiency but this effect may take years to manifest. It is becoming increasingly appreciated that RP is associated with accessory pudendal artery (APA) injury. APAs in some men are the major if not sole source of arterial inflow into the corpora cavernosa. Thus, injury to them may significant negatively impact upon long-term erectile function. Most authorities now accept APA injury as being a predictor of erectile function recovery. Finally, as mentioned above nerve injury may lead to structural damage to erectile tissue, but so too can the chronic absence of erections with the subsequent absence of cavernosal oxygenation as occurs during erection. It is postulated that the cavernosal smooth muscle requires exposure to arterial levels of oxygen to maintain its integrity. Thus, chronic lack of erectile activity irrespective of the treatment modality, may lead to further erectile tissue damage. Recent interest has focused on strategies that can minimize nerve injury (systemic neuro-modulatory drugs, perineural therapeutics) as well as protect the endothelium and cavernosal smooth muscle. Neuromodulatory drugs include families of agents that may be neuroprotective and/or neuroregenerative. The agents being explored in at least animal models, include immunophilin ligands (including cyclosporine, tacrolimus and rapamycin), erythropoetin, PARP inhibitors and PDE5i. Animal data are supportive of the potent neuromodulation that immunophilin ligands and erythropoietin can effect but evidence supporting the use of the other classes is currently lacking. Given the robust animal and human evidence.
Conflict of Interest: None disclosed
Financial Support/Funding: None disclosed
Recorded: Sydney, Australia, April 2007
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