Phosphodiesterase 5 inhibitors in rapid ejaculation: potential use and possible mechanisms of action

Rapid (premature) ejaculation (RE) is a very common sexual disorder. This condition may be primary or secondary to underlying disease. Control of RE has been primarily focused on behavioural therapy, topical anaesthetics, tricyclic antidepressants and selective serotonin reuptake inhibitors; however, an approved treatment does not exist. Recently, a number of clinical trials have studied the potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in the treatment of RE. Results of most of these studies have been encouraging. Available data indicate that there is clinical, anatomical, physiological, pharmacological and genetic evidence to explain the efficacy of PDE5 inhibitors in RE. The rationale for the use of PDE5 inhibitors in the treatment of RE could be due to possible peripheral and central mechanisms. Possible peripheral ejaculation retarding capabilities may include modulation of the contractile response of the vas deferens (VD), seminal vesicles (SV), prostate and urethra, induction of a state of peripheral analgesia, and prolongation of the total duration of erection. Possible central mechanisms may involve lessening of the central sympathetic output. Furthermore, there is evidence from knockout mice to explain the efficacy of PDE5 inhibitors in RE. Mice lacking the gene for endothelial nitric oxide synthase develop a condition similar to RE. On the other hand, mice lacking the gene for heme oxygenase-2 develop a condition similar to delayed ejaculation. This review also discusses the findings against the use of these agents in RE. In conclusion, a review of the literature suggests the potential usefulness of PDE5 inhibitors as a promising line of therapy in RE but further studies are needed.