Regenerative therapies for erectile dysfunction: a systematic review, Bayesian network meta-analysis, and meta-regression

Current guidelines advocate a shared decision-making process approach to erectile dysfunction management, and while there is growing interest in regenerative therapies such as stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy for erectile dysfunction, comparative data on the efficacy of these modalities are limited. This systematic review and network meta-analysis aims to compare stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy for managing erectile dysfunction and quantify their impact on the International Index of Erectile Function (IIEF). In January 2024, a systematic search of online databases was performed to identify randomized clinical trials related to stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy in erectile dysfunction. Eligible articles reported outcomes using the IIEF score. Data were inputted into Review Manager 5.4 for pairwise meta-analysis. Data were then used to build a network in R Studio. These networks were used to model 200 000 Markov Chains via MonteCarlo sampling. The results are expressed as standardized mean difference (SMD) with 95% credible intervals (CrI). Meta-regression was used to adjust for PDE5is use. Impact on the International Index of Erectile Function. A total of 16 studies involving 907 patients were analyzed. The standardized mean difference (SMD) vs control for stem cell therapy was 0.92 [95% CrI -0.49, 2.3]. For platelet-rich plasma, the SMD vs control was 0.83 [95% CrI 0.15, 1.5], and for low-intensity shockwave therapy, the SMD vs control was 0.84 [95% CrI 0.49, 1.2]. When stratifying low-intensity shockwave therapy by dose, the SMD vs control at 0.15 mJ/mm2 was 1.1 [95% CrI 0.36, 1.9], while at 0.09 mJ/mm2, it was 0.75 [95% CrI 0.26, 1.2]. Meta-regression adjusting for the administration of PDE5 inhibitors yielded non-significant results. The findings suggest that stem cells, platelet-rich plasma, and low intensity shockwave therapy, particularly at 0.15 and 0.09 mJ/mm2, may offer improvements in erectile function. The strength is the robust statistical methods. Limitations are in heterogeneity in control groups and follow-up durations among included studies. Shockwave therapy and platelet-rich plasma demonstrated statistically significant improvements, though the clinical relevance and extent of their impact remain questionable. Further research is necessary to determine the efficacy of stem cel