Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review

Abstract

Erectile dysfunction (ED) is a common complication after radical prostatectomy and results from trauma sustained by the cavernosal nerves. This is a major concern for patients and often affects treatment decisions. The likely mechanism for post-prostatectomy ED is through corporal venoocclusive dysfunction. There is an increasing amount of evidence to suggest that phosphodiesterase 5 inhibitors (PDE5 inhibitors), when given on a continuous long-term basis, can help to prevent and reverse ED after surgery. In this review article we will examine the pathophysiology of postprostatectomy ED and discuss the experimental and available clinical evidence for administering PDE5 inhibitors after prostatectomy. Erectile dysfunction is common following radical prostatectomyRecent data suggest that approximately 161 000 men per year undergo a radical prostatectomy in the United States. 1 It is thought that many more men who are diagnosed with early-stage prostate cancer would accept this surgical form of treatment for their newly diagnosed disease if it were not for the possibility of the development of erectile dysfunction (ED). This common complication after radical prostatectomy is largely due to trauma sustained by the cavernosal nerves and is still widely encountered even after the most recent advances in surgical technique to spare the nerves. [2][3][4][5] Of men that are potent before surgery, only about 40-74% of men regain sexual function. [4][5][6][7] In fact, 41.9% of men reported that their sexual performance was a moderate to large problem after surgery 7 and patients appear to value sexual function so highly that they are often willing to choose therapy that offers better potency with lower life expectancy than options that offer longer life expectancy and lower potency rates. 8 Radical prostatectomy seems to disrupt and/or damage the neurovascular mechanisms responsible for eliciting an erection thereby resulting in either temporary or permanent ED postoperatively. In its mildest form, apparent in a successful bilateral nerve sparing prostatectomy, the trauma resulting from surgical manipulation of the neurovascular bundles may result in a neuropraxia leading to temporary ED. The most severe form of ED results from a non-nerve sparing prostatectomy where both nerves are transected, either volitionally or unrecognized at the time of surgery, and this leads to the complete loss of neuroregulatory functions in the corpora cavernosa. CVOD is the most common form of ED following radical prostatectomyInjury to the cavernosal nerves results in the atrophy and degradation of the underlying cavernosal smooth muscle, which, besides resulting in ED, may also lead to a decrease in penile weight. 9 Histologically, such a neuropraxia/neurotomy leads to apoptosis of the cavernosal smooth muscle and an excessive deposition of collagen within the cavernosa, which clinically results in corporal

Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction

“…Surgical resection of the prostate also causes significant risk of erectile dysfunction due to trauma sustained by the cavernosal nerve (29). PDE-5 inhibitors have been shown to improve erectile function in men postradical prostatectomy (30)(31)(32).…”

On-demand use of erectile aids in men with preoperative erectile dysfunction treated by whole gland prostate cryoablation

“…The mechanism and role of erectile aids has been described in several articles. [18][19][20][21][22] In an animal model, use of a PDE5 inhibitor preserved smooth muscle content and endothelial function in penile tissue, and maintained nerve structures. 20 Therefore, we anticipate that even though cryoablation may potentiate bilateral cavernous nerve damage, PDE5 inhibitors can protect against further tissue Use of erectile aids following prostate cryoablation M Kimura et al damage following ablation and might enhance nerve regeneration.…”

The Role of PDE-5 Inhibitors in Prostate Cancer

“…All forms of prostate cancer therapy cause significant risk of erectile dysfunction due to trauma sustained by the cavernosal nerves (Rambhatla et al, 2008). As mentioned earlier, PDE-5 is the predominant enzyme in the corpus cavernosum and plays an essential role in vascular smooth muscle contraction through specific regulation of cGMP.…”

“…Their efficacy and safety have triggered a number of attempts to determine their potential benefits in non-urological conditions (Vlachopoulos et al, 2009). The rationale behind the use of PDE-5 inhibitors on a prolonged and continuous basis in the post-prostatectomy patient has never been fully and scientifically delineated (Rambhatla et al, 2008). The prolonged and continuous administration of vardenafil, prevented both fibrosis and loss of smooth muscle, subsequently reduced corporal veno-occlusive dysfunction (CVOD) following bilateral cavernosal nerve resection (Ferrini et al, 2006).…”