Do testosterone supplements enhance response to phosphodiesterase 5 inhibitors in men with erectile dysfunction and hypogonadism: a systematic review and meta-analysis.

Abstract

BackgroundCombining testosterone and phosphodiesterase 5 inhibitors (PDE5-Is) has become increasingly common in the treatment of men with erectile dysfunction (ED) and low testosterone levels, but combination therapy involving PDE5-Is and testosterone is highly debated, with strong reasons for and against argued by the various opinion leaders. PDE5-Is can be given prior to, alongside or after the commencement of any testosterone replacement therapy. Meanwhile, combination of PDE5-Is and testosterone is reported to better increase testosterone levels and thus improve International Index of Erectile Function (IIEF) score in hypogonadal men. The objective of this meta-analysis was to assess whether testosterone therapy (TTh) can possibly enhance the reaction to PDE5-Is in men with ED and hypogonadism.MethodsRelevant studies and available data were extensively collected form Medline, Embase, and Cochrane Library databases until June 2019. We calculated standard mean differences (SMDs) with their 95% confidence intervals (CIs) for IIEF including IIEF-5 and IIEF-EFD. Trial sequential analysis (TSA) was performed to explore whether the sample size of the accumulated evidence is sufficient.ResultsThere were 8 studies including 913 patients. The pooled SMD of erectile function (EF) component change was 0.663 [(0.299 to 1.027); P<0.0001], which concluded that combination therapy (TTh plus PDE5-Is) is superior to PDE5-Is monotherapy group. We also conducted a subgroup analysis according to trial follow-up, baseline serum total testosterone, baseline EF score and PDE5-Is type, which may explain for the underlying source of heterogeneity in part. The frequency of adverse events and change in PSA levels did not differ between the 2 groups. None of the patients experienced an increase in the prostate specific antigen (PSA) level above 4 ng/mL. Hematocrit increased significantly more in the testosterone group than in the placebo group but not greater than 0.54.ConclusionsIn summary, the present results confirm that combination therapy is effective and safe. TTh can enhance the reaction to PDE5-Is in men with ED and hypogonadism, but this effect also depends on the specific diagnosis and initial response to PDE5-Is. Most patients with adverse events during treatment are mild, and have a stable overall safety of combination therapy.