(561) Intracavernosal Botulinum Toxin for Erectile Dysfunction: A Comprehensive Systematic Review and Future Directions

Introduction Erectile dysfunction (ED) affects approximately 20% of men worldwide, significantly affecting their quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are the standard first-line treatment, a substantial number of patients are non-responders. Second line treatments, such as intracavernosal alprostadil, are effective but often limited by their invasive nature and the need for frequent injections. Intracavernosal onabotulinumtoxinA (BoNT-A) offers a promising new option. By inhibiting acetylcholine release, and norepinephrine and other neurotransmitters involved in detumescence, it facilitates cavernosal smooth muscle relaxation and enhances penile blood flow. Its effects may persist for up to six months following a single injection, potentially reducing treatment burden and improving adherence among men with refractory ED. Objective This systematic review aims to critically synthesize and evaluate the current evidence on the efficacy and safety of intracavernosal BoNT-A for the treatment of ED. By consolidating the existing evidence on this novel therapeutic approach, the review seeks to contribute to a more unified understanding of the topic and to encourage further research in this promising area of sexual medicine. Methods A systematic review was performed in accordance with the PRISMA guidelines and was prospectively registered in PROSPERO (CRD 420251087894). Literature searches were conducted in PubMed, Embase, Cochrane Library, Scopus, and Clinicaltrials.gov from inception until August 2025 using a combination of keywords and MeSH terms related to 'erectile dysfunction', 'intracaversonal injection' and 'botulinum toxin.' A total of 1,052 papers were identified, 557 were screened, 305 were deemed and 51 studies met the inclusion criteria. Due to significant heterogeneity interventions (e.g., BoNT-A dosage, co-therapies), patient populations, and reported outcomes, the data were not suitable for metaanalysis. Consequently, a narrative synthesis was performed to summarize the findings. Results Among the included studies, intracavernosal BoNT-A was associated with improvements in validated erectile function scores. Reported response rates, variably defined across studies, ranged from 40% to 77.5%. Several studies suggested that efficacy was higher in patients with mild-to-moderate ED and with repeated administration of 100U doses. The treatment exhibited a favorable safety profile. The most common adverse event was mild, transient penile pain (reported incidence 1.5%-6%). No studies reported serious systemic adverse events. The overall strength of the evidence was limited by significant heterogeneity among the included studies and their generally small sample sizes. Conclusions Based on this systematic review, intracavernosal onabotulinumtoxinA (BoNT-A) may be a beneficial therapeutic option for patients with refractory ED, offering potential improvements in sexual function while reducing the need for invasive therapies. Future large scale, placebo controlled studies are essential to confirm these benefits and standardize its clinical application. Disclosure No