Cell therapy for male sexual dysfunctions: systematic review and position statements from the European Society for Sexual Medicine.

Background: Cell therapy (CT) is a form of regenerative medicine under investigation for the management of male sexual dysfunction (MSD). Aim: We sought to perform a systematic review of published information on CT for MSD and provide an official position statements for the European Society for Sexual Medicine. Methods: A comprehensive bibliographic search on the MEDLINE, Web of Science, Scopus, and Cochrane Library databases was conducted in February 2023. Articles were selected based on the Population, Intervention, Comparator, Outcome, Study design (PICOS) model if they included male patients (P) undergoing CT (I) with or without comparison with other treatments (C) and evaluated the impact of CT on sexual function (O). Quantitative data were reported as found in the original studies (S). Level of evidence and grade of recommendation according to the Oxford Centre for Evidence-Based Medicine were assigned to each statement. Outcomes: Outcomes were determined based on assessment of erectile function, ejaculatory function, orgasmic function, sexual desire, and penile curvature. Results: A total of 19 studies and 421 patients were included. Most articles (n = 12, 63%) were case series, whereas a minority of papers (n = 6, 32%) had a comparative group; only 2 articles reported randomized controlled trials (RCTs) and 1 article reported a post hoc analysis of RCTs. Most articles (16, 84%) investigated patients with erectile dysfunction (ED). Improvements in the International Index of Erectile Function-Erectile Function Domain (IIEF-EF) or the IIEF 5-item version (IIEF-5) were found in 11/15 (73%) studies, with mean increases in IIEF-EF, mean IIEF-5, and median IIEF-EF between 8 and 14 points, 2 and 9 points, and 4.5 and 6 points, respectively. Two papers (20%) evaluated men with Peyronie's disease (PD). In both ot these articles penile curvature improvement and plaque volume reduction were described in all patients (n = 16, 100%). Objective measurements were performed in 1 study, which showed 10°-120° (15%-100%) curvature improvement and 90%-100% plaque reduction. Mild transient adverse events at the donor or administration sites were found in 7/16 (44%) papers on ED. Priapism was reported in one case (20%) and mild penile skin complications were reported in the majority of patients after CT for PD. No severe adverse events were described. Clinical Implications: Although high-quality evidence is lacking, CT appears to have potential benefits from application in patients with ED or PD. Strengths and Limitations: This report is to our knowledge the most comprehensive and up-to-date systematic review on the topic of CT for the management of MSD, including the position statements of the European Society for Sexual Medicine. Overall the assessment of available studies demonstrated low quality and significant heterogeneity. Conclusion: Preliminary findings support potential efficacy and safety of CT in patients with ED or PD. Low-quality papers, high methodological heterogeneity, uncertainty about the magnitude of the beneficial effects, and lack of long-term data limit the available evidence.