Abstract Introduction A substantial proportion of men with erectile dysfunction (ED) fail to achieve satisfactory erections with phosphodiesterase type 5 inhibitors (PDE5i), representing a challenging clinical subgroup. Low-intensity extracorporeal shock wave therapy (LI-ESWT) has emerged as a novel regenerative approach capable of restoring natural erectile function through neovascularization and endothelial repair. However, its role in men unresponsive to PDE5i remains to be clearly defined. Objective To evaluate the efficacy of LI-ESWT compared with sham therapy combined with PDE5i in men with ED who were non-responders to PDE5i treatment. Methods A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted through May 2025. Randomized controlled trials enrolling PDE5i non-responders and comparing ESWT monotherapy with sham + PDE5i were included. The primary outcome was the change in the International Index of Erectile Function-5 (IIEF-5) score at 1 and 3 months after treatment. Results Four studies comprising 345 participants met the inclusion criteria. ESWT significantly improved IIEF-5 scores compared with sham + PDE5i at 1 month (MD = 3.63; 95% CI 1.02–6.24; p = 0.006; I2 = 36%) and 3 months (MD = 3.21; 95% CI 2.94–3.50; p 0.001; I2 = 0%). The pooled overall effect confirmed a significant advantage for ESWT (MD = 3.22; 95% CI 2.94–3.50; p 0.001; I2 = 0%). Conclusions Low-intensity ESWT significantly improves erectile function in PDE5i non-responders, outperforming sham therapy with continued PDE5i use. This meta-analysis supports ESWT as a promising treatment option for patients with refractory vasculogenic ED, offering a regenerative alternative that addresses the underlying vascular pathology rather than providing transient pharmacologic enhancement. Disclosure No
Abdelshafi et al. (Mon,) studied this question.