Premature ejaculation (PE) remains a highly prevalent and complex syndrome both to define and effectively treat in millions of men worldwide. While treatment is largely via pharmacotherapy with off-label indications, a recent systematic review sought to investigate the therapeutic role of PDE5 inhibitors.
Twenty-nine manuscripts that examined proposed mechanisms of action and 14 manuscripts that reported data from clinical trials were identified and reviewed. The review identified commonly reported supposed, central, and peripheral mechanisms of action of PDE5 inhibitors, predominantly centered on the role of nitrous oxide (NO) relative to second messenger pathways (e.g. CGMP) in the central nervous system and its relationship to smooth muscle in peripheral tissue.
Two different meta-analyses were performed including 1) PDE5 inhibitor monotherapy compared to placebo and 2) PDE5 inhibitor + SSRI versus placebo. The first meta-analysis found a significant effect of the PDE5 inhibitor treatment compared to placebo, while there was greater variability in the results in the group that received combination therapy. Overall, there was felt to be insufficient clinical evidence to support the use of PDE5 inhibitors in the treatment of PE.
Reference: Asimakopoulos AD, Miano R, Agro EF, et al. Does current scientific and clinical evidence support the use of phosphodiesterase type 5 inhibitors for the treatment of premature ejaculation? A systematic review and meta-analysis. J Sex Med 2012;9:2404-2416.