Systematic Review on the Safety and Effectiveness of Restorative Therapies for Erectile Dysfunction

ISSM-commissioned review of 36 studies finds mixed, inconsistent evidence for all restorative ED therapies, with 78% of trials failing to report clinically meaningful outcomes

Journal: The Journal of Sexual Medicine | Published: 2026-06-05 | Type: Systematic Review | PMID: 42251759 Authors: Taylor Kohn (Baylor College of Medicine), El-Sakka Ahmed (Suez Canal University), Facio Fernando (FAMERP Brazil), Martinez Salamanca Juan I (Lyx Institute / Universidad Francisco de Vitoria), Raheem Omer (Cleveland Clinic Abu Dhabi), Park Kwangsung (Chonnam National University Hospital), Lin Guiting (UCSF), Goldstein Irwin (San Diego Sexual Medicine), Cocci Andrea (University of Florence), Hamel Candyce (independent evidence synthesis consultant) Funding/COI: Not listed for either

Summary

This International Society for Sexual Medicine (ISSM)-commissioned systematic review screened MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL for comparative studies (2010–2023) on four restorative ED therapies: focused and radial low-intensity extracorporeal shockwave therapy (Li-ESWT), intracorporal stem cell injections, platelet-rich plasma (PRP) injections, and low-intensity pulsed ultrasound. Of 36 included studies — 30 RCTs, 6 non-randomized — focused shockwave therapy dominated the literature with 23 studies, yet results versus sham remained split. The authors conclude that no restorative therapy has enough clean evidence to support routine clinical use.

Claims

• 36 studies included: 30 RCTs, 6 non-randomized observational studies
• 23 of 36 studies evaluated focused shockwave therapy specifically
• Results for focused Li-ESWT vs. sham were explicitly described as "mixed" — some trials reported statistically significant improvements in erectile function scores; others found no significant difference
• 78% of included studies did not report or compare the minimal clinically important difference (MCID) in erectile function
• Among the minority that did report MCID, additional methodological concerns were identified: use of MCID thresholds for instruments without a validated MCID (specifically the IIEF-5), and pooling patients with mixed ED severity in combined MCID reporting
• Evidence for stem cell injections, PRP, and low-intensity pulsed ultrasound was described as "limited and inconsistent"
• Heterogeneity of treatment protocols was cited as a major barrier to drawing conclusions across studies

Study Quality

This is a systematic review covering four major databases with a defined search window (January 2010–November 2023), dual-reviewer study selection and data extraction, and formal bias assessment using Cochrane Risk of Bias for RCTs and ROBINS-I for non-randomized studies — a methodologically sound approach for a review of this type. The choice to restrict to comparative studies (rather than single-arm before/after designs) appropriately limits inclusion to trials with at least a control condition.

The review is, however, ultimately constrained by the quality of its constituent studies. The 78% MCID non-reporting rate means that the majority of the underlying RCTs measured whether scores changed statistically, not whether patients improved in any way that matters clinically. A trial showing p < 0.05 on IIEF when no validated MCID exists for that instrument is statistical noise dressed up as evidence.

Red Flags

• Funding and conflicts of interest are not disclosed for the review itself — notable given several authors (Goldstein, Martinez Salamanca) are prominent figures in the commercial sexual medicine space where shockwave devices are marketed
• 78% of underlying trials failed to report MCID — a foundational outcome measure; this is a systemic failure of the evidence base, not just individual studies
• The IIEF-5 (5-item version) was used as an outcome instrument in studies that applied MCID thresholds, but no validated MCID exists for the IIEF-5 specifically — that threshold was borrowed from the full IIEF and applied incorrectly
• Heterogeneous treatment protocols across shockwave studies prevent meaningful pooled conclusions even where individual results were positive
• Study search window ends November 2023; published June 2026 — a 2.5-year lag during a period of active trial publication in this space

Strengths

• ISSM commissioning adds institutional accountability to the review's conclusions
• Dual-reviewer selection and extraction reduces individual reviewer bias
• Formal bias assessment tools (Cochrane RoB, ROBINS-I) applied consistently
• Restriction to comparative studies is the right methodological call — excludes the weakest evidence tier
• Covers all four major restorative therapy categories rather than focusing narrowly on shockwave alone
• Authors are direct that evidence is insufficient for routine clinical use, despite clearly representing a community with professional investment in these therapies

Verdict

This review is doing the right thing: an ISSM-commissioned team that includes major commercial advocates for restorative therapies is telling you the evidence isn't there yet. That's worth noting. The systematic methods are solid, but the review is hamstrung by what it's reviewing — a literature where 78% of RCTs didn't bother to measure whether their statistically significant score changes meant anything to patients. The shockwave therapy result is genuinely mixed, not "promising with caveats," and the stem cell and PRP evidence is thin by the review's own characterization. The missing COI disclosure is the one thing that should give a reader pause: several authors are active in this commercial space, and the absence of a declaration is a gap in an otherwise rigorous document.