Efficacy and safety of short- and long-term, regular and on-demand regimens of phosphodiesterase type 5 inhibitors in treating erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis

Background: We performed a meta-analysis to evaluate the efficacy and safety of short-term (≤6 months) and long-term (>6 months), regular (OaD) and on-demand (PRN) regimens of phosphodiesterase type 5 inhibitors (PDE5-Is) in treating erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NSRP). Methods: We conducted a literature search in August 2016. Sources included PubMed, EMBASE, and MEDLINE databases. The main outcome was International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, and the secondary outcome was treatment-emergent adverse events (TEAEs). Results: Eight articles involving 13 randomized controlled trials (RCTs) were used in this analysis: they suggested that PDE5-Is can improve the IIEF-EF distinctly in comparison with placebo in short and long term (mean difference [MD]: 2.26, 95% confidence interval [CI]: 1.45–3.08, P <0.00001, and MD: 4.5, 95% CI: 3.6–5.4, P <0.00001), and long-term use of PDE5-Is (>6 months) can improve the IIEF-EF distinctly in comparison with short-term use of PDE5-Is (≤6 months) (MD: 3.9, 95% CI: 3.01–4.8, P <0.00001). OaD of PDE5-Is significantly improved the IIEF-EF compared to placebo in short and long term (MD: 4.08, 95% CI: 3.2–4.97, P <0.00001, and MD: 4.74, 95% CI: 3.79–5.69, P <0.00001). No significant differences were found in IIEF-EF changes between PRN and placebo (≤6 months) (MD: 2.64, 95% CI: −0.87 to 6.14, P =0.14), and between PRN and OaD group (>6 months) (MD: −0.58, 95% CI: −9.86 to 8.74, P =0.91). There were more TEAEs in PDE5-Is group in comparison with placebo (odds ratio [OR]: 1.55, 95% CI: 1.26–1.91, P <0.0001), and TEAEs in OaD group were not significantly different from those seen in PRN group (OR: 1.05, 95% CI: 0.78–1.4, P =0.77). Conclusion: Our meta-analysis suggests that PDE5-Is are efficient and safe for treatment of ED after NSRP, and we should choose the regular regimen for short term and regular or on-demand regimen for long term. Further high-quality RCTs are needed to validate this result. Keywords: erectile dysfunction, meta-analysis, nerve-sparing radical prostatectomy, phosphodiesterase type 5 inhibitors