The Role of Phosphodiesterase Type 5 Inhibitors in the Management of Premature Ejaculation: A Critical Analysis of Basic Science and Clinical Data

Objectives: To assess the usefulness of the phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of premature ejaculation (PE) and to describe possible mechanisms to explain their effect. Methods: A MedLine search was performed for peer-reviewed articles on the role of PDE5-Is in managing PE. No meta-analysis method was used. Results: Five manuscripts that examined the efficacy of PDE5-Is in the treatment of PE were retrieved. Three studies used sildenafil as monotherapy and two used it in combination with a serotonin selective reuptake inhibitor (SSRI). Three studies demonstrated a beneficial effect of sildenafil in the treatment of PE, as measured by intravaginal ejaculatory latency time (IELT) and by different questionnaires assessing the patients' subjective feelings of ejaculatory control, sexual satisfaction, and anxiety. One study showed the superiority of sildenafil compared to other modalities. Two studies showed that combination therapy of paroxetine and sildenafil was better than paroxetine alone. One study did not demonstrate a beneficial effect of sildenafil in prolonging IELT, but showed that sildenafil improved patients' perception of ejaculatory control. Another study showed that topical anesthetics were better than sildenafil in the treatment of PE but did not use IELT or a validated questionnaire to measure the efficacy of treatment. Several possible mechanisms could explain effectiveness of the PDE5-Is for treatment of PE: centrally, through the effect on the nitric oxide/cyclic guanosine monophosphate pathway; peripherally by causing relaxation of smooth muscle in the vas deferens, seminal vesicles, prostate, and urethra and inhibition of adrenergic transmission; or locally by inducing peripheral analgesia. Another possibility might be prolongation of the duration of erection. Conclusions: Encouraging evidence supports the role of PDE5-Is for treating PE. Possible therapeutic mechanisms of action of PDE5-Is are multiple and complex and include central and peripheral effects. A large population, multicenter, randomized, double-blind, placebo-controlled study is needed to elucidate the efficacy of PDE5-Is in the treatment of PE.