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.

Erectile dysfunction treatment with Phosphodiesterase-5 Inhibitors: Google trends analysis of last 10 years and COVID-19 pandemic

Objectives: We aimed to analyze the trend change of the most popular Phosphodiesterase-5 Inhibitors (PDE5i) over time and geography by using Google Trends (GT) data in 10 years period and COVID-19 pandemic. Materials and methods: GT is able to generate a “line-graph”, showing how interest has increased or decreased over a period within specific territories. The search values for specific terms are indexed as relative search volume (RSV), which is presented on a scale from 0-100. Avarage annual percentage change (AAPC) and RSV were analyzed to evaluate gain or loss of interest in trends. Search terms were generated for Food and Drug Administration (FDA)-approved PDE5i; tadalafil, sildenafil, vardenafil, avanafil, and their most-used brand names. The data was within “worldwide” from 1 January 2010, to 31 December 2020, using the ‘‘global’’ query category. Results: The overall interest in PDE5i has doubled. Sildenafil has become the most trend PDE5i of today with a regular increase (AAPC: 0.016, p < 0.01). Although the search trend of tadalafil remained almost constant until 2014, the rate of increase in the last 6 years raised and tadalafil has become the 2nd most popular PDE5i recently (AAPC: 0.007, p < 0.01). For vardenafil there has been a decreased interest (AAPC: -0.009, p < 0.01). There is no significant change in avanafil trend (AAPC: 0.000, p: 0.5). All PDE5i interest on GT decreased notably from February to June 2020. But after June, search trends reached the level before the COVID-19 period in a month. Conclusions: These findings show us, with its increasing prevalence, erectile dysfunction (ED) has become a major public health problem. People from different geographies search the internet for ED treatment options. Patients should be informed that ED may be the first sign of many comorbid diseases, and patients with ED should be referred to a health institution for diagnosis and treatment.