Phosphodiesterase Type 5 Inhibitors for Premature Ejaculation: A Systematic Review and Meta-analysis

Abstract

Context: Phosphodiesterase type 5 inhibitors (PDE5-Is) are prescribed off-label for the treatment of premature ejaculation (PE).

Objective: To systematically review the evidence from randomised controlled trials (RCTs) for PDE5-Is in the management of PE.

Evidence acquisition: Medline and other databases were searched through September 2015. Quality of RCTs was assessed. Intravaginal ejaculatory latency time (IELT) data were pooled in a meta-analysis. Heterogeneity was assessed.

Evidence synthesis: Fifteen RCTs were included. The majority were of unclear methodological quality. Pooled IELT evidence suggests that PDE5-Is are significantly more effective than placebo (231 participants, p<0.00001), that there is no difference between PDE5-Is and selective serotonin reuptake inhibitors (SSRIs; 405 participants, p=0.50), and that PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone (521 participants, p=0.001); however, high levels of statistical heterogeneity are evident (I² ≥ 40%). Single-RCT evidence suggests that sildenafil is significantly more effective than the squeeze technique, but both lidocaine gel and tramadol are significantly more effective than sildenafil. Sildenafil combined with behavioural therapy is significantly more effective than behavioural therapy alone. Sexual satisfaction and ejaculatory control appear to be better with PDE5-Is compared with placebo and with PDE5-Is combined with an SSRI compared with an SSRI alone. Adverse events are reported with both PDE5-Is and other agents.

Conclusions: PDE5-Is are significantly more effective than placebo and PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone at increasing IELT and improving other effectiveness outcomes; however, heterogeneity is evident across RCTs. The methodological quality of the majority of RCTs is unclear.

Patient summary: We reviewed phosphodiesterase type 5 inhibitors (PDE5-Is) for treating premature ejaculation. We found evidence to suggest that PDE5-Is are effective compared with placebo and that PDE5-Is combined with an SSRI are more effective than an SSRI alone. Adverse events are reported with PDE5-Is and other agents; however, the quality of the evidence is uncertain.

Trial registration: PROSPERO registration number CRD42013005289.

Keywords: Phosphodiesterase type 5 inhibitors; Premature ejaculation; Sexual health.

Figure 1. PDE5 inhibitors vs. placebo - forest plot of IELT outcomes

PC, pre-coitus

Figure 2. PDE5 inhibitors vs. SSRIs - forest plot of IELT outcomes

Figure 3. PDE5 inhibitors plus SSRIs vs. SSRIs - forest plot of IELT outcomes

Figure 4. PDE5 inhibitors vs. squeeze technique, lidocaine gel or tramadol - forest plot of IELT outcomes