Analysis of the Impact of Androgen Deprivation Therapy on Sildenafil Citrate Response Following Radiation Therapy for Prostate Cancer

Abstract

Androgen deprivation seems to exert a deleterious effect on erectile function in men undergoing radiation therapy for prostate cancer. This was observed in men treated with conformal external beam and brachytherapy at short-term, medium term and long-term followup.

The Role of PDE-5 Inhibitors in Prostate Cancer

“…A long-term single daily dose of tadalafil also prevented CVOD and the underlying corporal fibrosis in the rat caused by cavernosal nerve damage, as effectively as the previously reported continuous treatment with vardenafil or sildenafil, through a cGMP-related mechanism that appeared to be independent of iNOS induction (Kovanecz et al, 2008b). Sildenafil treatment was also effective for improving erectile function in men with post-radiation, particularly, in the early stages after the completion of radiation (Teloken et al, 2007). Treatment with exisulind, another PDE-5 inhibitor, at 250 mg bid had been evaluated in men with prostate cancer following radical prostectomy (Goluboff et al, 2001).…”

“…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. There is an increasing amount of evidence suggesting that PDE-5 inhibitors significantly improve erectile function in men after post-radical prostatectomy (Mydlo et al, 2005;Ohebshalom et al, 2005;Schiff et al, 2006;Teloken et al, 2007). Their efficacy and safety have triggered a number of attempts to determine their potential benefits in non-urological conditions (Vlachopoulos et al, 2009).…”

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). We have established a powerful cardioprotective effect of PDE-5 inhibitors in animal models (33).…”

Combination therapy with phosphodiesterase type V inhibitors and testosterone

“…In men with diabetes and ED, the mean total testosterone level was signifi cantly lower in those who did not respond compared with those who responded properly (respectively, 1.99 vs 5.36 ng/mL) [ 19 ]. In patients with ED following radiation therapy for prostate cancer, sildenafi l effi cacy was lower in those with androgen deprivation therapy compared with those without it [ 20 ]. In an RPCT of sildenafi l in 40 men (mean age, 63.3 y) who screened positively for symptoms of TD on the Androgen Defi ciency in Aging Males (ADAM) questionnaire, the IIEF total score increased signifi cantly more in those with a normal testosterone level than in those with TD [ 21 ].…”