Abstract Introduction Erectile dysfunction (ED) is common and can strongly affect men's well-being. While phosphodiesterase type 5 inhibitors (PDE-5i) offer effective symptomatic relief, they do not restore natural erectile function for all patients. Low-intensity extracorporeal shock wave therapy (LI-ESWT) has been proposed as a regenerative option, but its comparative efficacy remains unclear. Objective To comprehensively evaluate the efficacy of LI-ESWT for ED through multiple direct comparisons: LI-ESWT versus sham treatment, LI-ESWT versus PDE-5i monotherapy, combination therapy (LI-ESWT plus PDE-5i) versus PDE-5i monotherapy, and combination therapy versus LI-ESWT monotherapy, with subgroup analyses in vasculogenic ED and PDE-5i non-responders. Methods A systematic review and network meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched through May 2025 for randomized controlled trials evaluating LI-ESWT in men with ED. Included studies compared LI-ESWT monotherapy versus sham, LI-ESWT versus PDE-5i, LI-ESWT plus PDE-5i versus PDE-5i alone, and LI-ESWT plus PDE-5i versus LI-ESWT alone. Primary outcomes were changes in International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS) assessed at 1-, 3-, 6-, and 12-month follow-up. Random-effects models calculated pooled mean differences with 95% confidence intervals. Heterogeneity was quantified using I² statistics, and subgroup analyses examined vasculogenic etiology and PDE-5i non-responder populations. Results Twenty-two randomized controlled trials were included. LI-ESWT demonstrated significant superiority over sham treatment across all timepoints for IIEF-5 (1 month: MD=1. 89, 95% CI 0. 40–3. 39, p=0. 01; 3 months: MD=2. 24, 95% CI 0. 96–3. 52, p0. 001; 6 months: MD=3. 51, 95% CI 1. 17–5. 85, p=0. 003). When compared directly with PDE-5i monotherapy, PDE-5i showed superior short-term efficacy at 1 month (MD=-2. 75, 95% CI -4. 34 to -1. 16, p=0. 0007), but by 3 months, no significant difference existed between treatments (MD=-0. 09, 95% CI -1. 71 to 1. 54, p=0. 92). Combination therapy (LI-ESWT plus PDE-5i) provided significantly greater IIEF-5 improvement versus LI-ESWT alone at 1, 3, and 6 months (p0. 001), but not at 12 months (p=0. 35). However, adding LI-ESWT to PDE-5i in patients already on PDE-5i showed no additional benefit at 1 month (MD=1. 86, 95% CI -1. 93 to 5. 65, p=0. 34). In vasculogenic ED specifically, LI-ESWT monotherapy significantly outperformed sham at both 1 and 3 months, while combination therapy offered no advantage over PDE-5i alone. Notably, LI-ESWT demonstrated significant efficacy in PDE-5i non-responders compared with continued sham plus PDE-5i treatment (1 month: MD=3. 63, 95% CI 1. 02–6. 24, p=0. 006; 3 months: MD=3. 21, 95% CI 2. 94–3. 50, p0. 001). Conclusions LI-ESWT is an effective regenerative treatment for erectile dysfunction. It is superior to sham, matches PDE-5i effectiveness by 3 months, and helps patients unresponsive to PDE-5i. Combined therapy gives short-term benefits but no long-term advantage. LI-ESWT should be considered for both treatment-naïve and PDE-5i-refractory patients, while further research is needed to optimize protocols and candidate selection. Disclosure No
Abdelshafi et al. (Mon,) studied this question.
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