Placebo response in intralesional injection therapy for Peyronie's disease: a systematic review and meta-analysis of published prospective clinical trials

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• Picked for Urology (top studies of the week, 30 August 2026): Placebo response meta‑analysis in Peyronie's disease injection trials

Abstract

INTRODUCTION: Intralesional injection therapy represents a cornerstone of the conservative management for Peyronie's disease (PD), aiming to reduce penile curvature and plaque-related deformities through the localized administration of various pharmacological agents. Although multiple clinical trials have demonstrated curvature improvements following these interventions, the actual magnitude of curvature change attributable to the placebo response remains unclear. This study aimed to quantify penile curvature changes observed in placebo arms of randomized controlled trials evaluating intralesional injection therapies for PD. METHODS: A systematic literature search was performed on PubMed and Scopus using the terms "Peyronie's disease," "induratio penis plastica," "injection," and "placebo" (PROSPERO ID: CRD420251159277). The search retrieved 1371 records from PubMed and 1005 records from Scopus for injection and placebo terms. Random-effects meta-analysis (REML-Hartung-Knapp adjustment) was conducted to estimate the standardized mean difference in curvature change between baseline and end of therapy in placebo arms. A meta-regression model evaluated the influence of mean age, penile modeling, and number of injections on curvature change. Risk of bias was assessed using the RoB 2 tool. RESULTS: After screening, 6 RCTs and 1 non-randomized controlled-trial comparing active drug versus placebo were included with a total of 382 patients in placebo arms. The mean baseline curvature ranged from 33.5° to 50.9°, with follow-up durations between 4 and 36 weeks. The mean number of injection was 13.4. Across the seven included studies, placebo-treated patients experienced a modest but statistically significant reduction in penile curvature. The pooled mean difference was -5.1° (95% CI -8.0° to -2.3°; P = .003), corresponding to an standardized mean difference of -0.38 (95% CI -0.55 to -0.20). No significant associations were observed between curvature change and mean age, number of injections, or penile modeling in meta-regression analyses. Risk of bias was overall moderate, mainly due to limited blinding and suboptimal randomization. Data on plaque size and pain were insufficient for pooled analysis. CONCLUSIONS: This meta-analysis demonstrates that intralesional placebo injections alone are associated with an average curvature improvement of ~5°. This effect size should be considered when designing and interpreting clinical trials investigating novel intralesional therapies for PD.

Abstract as published, via PubMed.