Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails.
Level 1 - systematic review of randomized trials
Systematic review of randomized controlled trials and clinical studies
PubMed 30711478 · doi:10.1016/j.sxmr.2018.11.007
What was done
Authors systematically searched PubMed and Embase for quantitative studies evaluating second-line oral combination therapies in patients with erectile dysfunction (ED) who failed phosphodiesterase type 5 inhibitor (PDE5i) monotherapy. Outcomes were assessed using the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD).
What was found
The abstract reports no specific numerical scores, ranges, or effect sizes. Key reported findings: - Chronic treatment with tadalafil alone achieved similar IIEF-5 score improvements compared to chronic tadalafil combined with on-demand sildenafil. - None of 3 randomized controlled trials (RCTs) found combination therapy of androgen plus PDE5i to be superior to PDE5i monotherapy in nonresponders, though the combination appeared safe. - In 1 RCT, combining a PDE5i with an alpha-1-adrenoceptor antagonist showed no superiority over PDE5i monotherapy. - Six additional studies examined other combinations (such as metformin, folic acid, or 5-alpha-reductase inhibitors), but the abstract noted that efficacy remains uncertain and requires further research.
Why it matters
Approximately 30% to 40% of patients with ED fail initial PDE5i monotherapy. This review demonstrates that oral combination strategies currently lack evidence of superior efficacy over monotherapy, indicating a persistent unmet need before escalating to invasive treatments like intracavernosal injections.
Limits
The abstract reports no numerical values, confidence intervals, or total participant counts. The evidence base for each specific combination is very limited (only 1 to 3 RCTs per drug class), restricting the strength of the conclusions.
Cited by
- contradicts Oral erectile dysfunction medications fail in approximately 15% of men on initial use.