Systematic review on the safety and effectiveness of restorative therapies for erectile dysfunction

Several restorative (or regenerative) therapies have been proposed in the past 15 years to reverse the underlying pathophysiology associated with erectile dysfunction.

The aim of this International Society for Sexual Medicine-commissioned review of restorative therapies for erectile dysfunction was to systematically review the literature to determine the safety and efficacy of these therapies.

A systematic review of MEDLINE, EMBASE, CINAHL, and the Cochrane CENTRAL database of controlled trials was performed to identify comparative studies published from January 2010 through November 2023. Two reviewers performed study selection and data extraction. Five restorative therapies were assessed: low-intensity extracorporeal shockwave therapy (focused or radial), intracorporal stem cell injections, intracorporal platelet-rich plasma injections, and low-intensity pulsed ultrasound. Outcomes of interest included adverse events and changes in validated erectile function symptom scores. The Cochrane Risk of Bias and ROBINS-I tools were used to evaluate the risk of bias of randomized controlled trials and observational studies, respectively.

A total of 36 studies were included, 30 randomized controlled trials and 6 non-randomized studies. Most of these studies (n = 23) evaluated focused shockwave therapy. Results for focused shockwave therapy compared to sham were mixed. While some sham-controlled trials reported statistically significant improvements in erectile function scores favoring focused shockwave therapy, other trials found no significant difference between groups. Additionally, many studies (78%) did not report or compare the minimal clinically important difference (MCID) in erectile function. Among those that did, further methodological concerns including the use of MCID thresholds with instruments for which no MCID has been validated (ie, IIEF-5) and reporting a combined MCID in cohorts with mixed severity of erectile function limit confidence in the result. Other restorative therapies also report limited and inconsistent evidence.

The data regarding focused shockwave therapy for erectile dysfunction remains mixed, with some trials showing benefit compared to sham and others showing no difference. The heterogeneity of treatment protocols, methodological limitations across studies, and inconsistent MCID reporting preclude definitive conclusions about clinical efficacy. All restorative therapies, including focused shockwave therapy, require further investigation in well-designed trials with standardized protocols and validated outcome measures before routine clinical use can be recommended.