Impact of Testosterone Therapy on hypogonadal patients unresponsive to phosphodiesterase-5 inhibitors alone: A systematic review and a meta-analysis

Background Phosphodiesterase-5 inhibitors as the first-line treatment for erectile dysfunction, when patients with hypogonadism fail to respond to phosphodiesterase-5 inhibitors, the beneficial of addition testosterone therapy is a major concern for clinicians. The objective of this study was to collect and summarize the evidence that evaluated the benefit of addition testosterone therapy in hypogonadism fail to respond to phosphodiesterase-5 inhibitors. Methods Electronic literature searches of Cochrane Library, PubMed, MEDLINE and EMBASE databases were conducted up to October 2020 and included randomized controlled trials. Specifically, we were looking for papers where Erectile Function Domain Score differences between pre and post-treatment were used as the primary outcome after treatment of testosterone therapy alone, phosphodiesterase-5 inhibitors therapy alone, or a dual treatment of both testosterone therapy and phosphodiesterase-5 inhibitors. Secondary outcomes included the number of phosphodiesterase-5 inhibitors non-responders who subsequently reported a satisfactory treatment of dual treatment with testosterone therapy and phosphodiesterase-5 inhibitors. Results A total of 4 studies that met our criteria, consisting of 326 patients. The Erectile Function Domain Score was significantly higher after treatment of testosterone combine with phosphodiesterase-5 inhibitors(4.88[4.18–5.57]), phosphodiesterase-5 inhibitors with placebo(3.15[1.82–4.47]), and testosterone monotherapy (2.04[0.38–3.71]) compared with baseline. Dual treatment with testosterone and phosphodiesterase-5 inhibitors significantly improved Erectile Function Domain Score when compared with testosterone monotherapy (3.16, 95% CI: 1.79–4.53), Of 41.7% patients in the dual treatment group reported an improvement, compared to only 33.0% in phosphodiesterase-5 inhibitors treatment group. Conclusions Combination therapy of testosterone and phosphodiesterase-5 inhibitors seems most effective in men with both erectile dysfunction and hypogonadism who initial unrespond to phosphodiesterase-5 inhibitors.