Comparative efficacy of combination therapy including regenerative therapies versus monotherapy for erectile dysfunction: A systematic review and meta-analysis.

BACKGROUND AND

OBJECTIVE

The Current European Association of Urology guidelines do not provide recommendation for combination of regenerative therapies with standard therapies for erectile dysfunction. The aim of this study was to compare the efficacy of combined regenerative therapy with monotherapy for erectile dysfunction.

METHODS

A systematic review and meta-analysis were conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The protocol was registered on PROSPERO (CRD42024522307). Randomized controlled trials and prospective/retrospective studies comparing combination therapies (low-intensity external shockwave therapy, platelet-rich plasma, stem cell therapy with phosphodiesterase-5 inhibitors, or other treatments) with monotherapy were included. Erectile function was assessed using the International Index of Erectile Function-5 and Erection Hardness Scale. Groups were compared using standardized mean difference. Subgroup analyses based on treatment type, erectile dysfunction cause, and follow-up duration were also conducted. Risk of bias was assessed using risk of bias 2 and Robins-I tools.

KEY FINDINGS AND LIMITATIONS: Of 1416 articles screened, eight studies involving 553 patients met the inclusion criteria. All studies included phosphodiesterase-5 inhibitors and low-intensity external shockwave therapy as regenerative treatment, with no studies on stem cell therapy or platelet-rich plasma. After treatment, no significant difference in International Index of Erectile Function scores was found between combination and monotherapy groups. However, subgroup analysis revealed that combination therapy showed a statistically significant improvement compared to low-intensity external shockwave therapy alone (standardized mean difference: 0.61; 95% confidence interval: 0.13‒1.09; p = 0.013). A statistically significant improvement was found in vasculogenic (standardized mean difference: 0.65; p < 0.001) and diabetic cases (standardized mean difference: 1.05; p < 0.001).

CONCLUSIONS AND CLINICAL IMPLICATIONS: Combination of phosphodiesterase-5 inhibitors and intensity external shockwave therapy resulted in significant improvement of International Index of Erectile Function compared to intensity external shockwave therapy alone. However, the risk of bias was high because of the low quality of the studies.

PATIENT SUMMARY: Combination of phosphodiesterase-5 inhibitor with intensity external shockwave therapy significantly improved erectile function, especially in patients with vasculogenic erectile dysfunction or diabetes.