Abstract Introduction Erectile dysfunction (ED) is a prevalent condition affecting men worldwide, often associated with endothelial dysfunction and impaired penile blood flow. While phosphodiesterase type 5 inhibitors (PDE5i) are the first-line pharmacologic therapy, they primarily offer symptomatic relief without addressing underlying vasculogenic deficits. Low-intensity extracorporeal shock wave therapy (LI-ESWT) has emerged as a regenerative treatment promoting neovascularization and endothelial repair. Combining LI-ESWT with PDE5i has been proposed to achieve synergistic effects, yet clinical evidence remains inconsistent regarding the magnitude and duration of benefit. Objective To compare the efficacy of LI-ESWT alone versus LI-ESWT combined with PDE5i in improving erectile function in men with ED, based on validated functional outcomes. Methods A systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted through May 2025. Randomized controlled trials (RCTs) comparing LI-ESWT with and without concurrent PDE5i use were included. The primary outcome was change in the International Index of Erectile Function-5 (IIEF-5) score, while secondary outcomes included changes in Erection Hardness Score (EHS) at 1-, 3-, 6-, and 12-month follow-up Results Four studies met the inclusion criteria. Combination therapy with ESWT + PDE5i resulted in significantly greater improvement in IIEF-5 scores at 1 month (MD = 2.79; 95% CI 1.47–4.12; p 0.001), 3 months (MD = 3.21; 95% CI 2.92–3.50; p 0.001), and 6 months (MD = 3.28; 95% CI 1.19–4.38; p 0.001), but not at 12 months (MD = 1.20; 95% CI –1.34–3.74; p = 0.35). Similarly, EHS scores were higher in the combination group at 3 months (MD = 0.29; 95% CI 0.21–0.37; p 0.001) and 6 months (MD = 0.30; 95% CI 0.22–0.38; p 0.001). No significant subgroup differences were observed across time points (p 0.05). Conclusions The combination of low-intensity ESWT and PDE5 inhibitors provides superior short- and mid-term improvement in erectile function and penile rigidity compared with ESWT alone, supporting a synergistic interaction between regenerative and pharmacologic mechanisms. However, the advantage appears to diminish by 12 months, highlighting the need for optimized treatment protocols and long-term follow-up studies to define the durability of clinical benefits. Disclosure No
Abdelshafi et al. (2026) studied this question.