From Growth Factors to an Immune-Centric Approach: A Systematic Review of the Biological and Clinical Evidence for Platelet-Rich Plasma in Erectile Dysfunction

Background: Intracavernosal platelet-rich plasma (PRP) is increasingly used for erectile dysfunction (ED), despite the absence of standardized biological characterization and clear dose definitions. This systematic review evaluates the clinical efficacy of PRP in ED while integrating emerging immune-centric mechanistic evidence. Methods: Following PRISMA 2020 guidelines, randomized controlled trials (RCTs) and prospective studies (2020–2025) investigating intracavernosal PRP in adult men with ED were identified across major databases. Validated outcomes included International Index of Erectile Function (IIEF-EF or IIEF-5), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP), and penile Doppler parameters. Preclinical data were narratively integrated to contextualize biological plausibility. Results: Fourteen clinical studies met the inclusion criteria (six RCTs, eight prospective cohorts). Across most studies, PRP produced clinically relevant within-patient improvements, and three RCTs demonstrated minimal clinically important difference (MCID) responder rates compared with placebo. However, other trials showed comparable improvements in placebo arms, underscoring substantial contextual effects. Safety was consistently favourable. Marked heterogeneity in blood volume processed (10–120 mL), injected PRP volume (3–12 mL), preparation systems, and session protocols precluded cross-study comparability. Critically, no study reported platelet dose, leukocyte subsets, peripheral blood mononuclear cell (PBMNC) content, or red blood cell contamination. Preclinical models consistently demonstrate that PRP restores erectile function through angiogenic, neuroprotective, and immunomodulatory mechanisms, including CXCL5-mediated monocyte recruitment and M1-to-M2 macrophage polarization. Conclusions: Intracavernosal PRP shows promising short-term efficacy signals and a favourable short-term safety profile in mild-to-moderate vasculogenic ED, but current evidence is limited by profound biological and methodological heterogeneity. PRP should be reconsidered as an immune-regenerative intervention requiring dose-defined, composition-defined, and mechanistically informed randomized trials. Interpretation of these findings is constrained by the absence of formal risk-of-bias assessment for non-randomized studies, substantial clinical and biological heterogeneity across trials, and the lack of standardized PRP characterization.