{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:24:49Z","timestamp":1791440689358,"version":"4.3.3"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: 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, as well as 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. Methods: A systematic review was performed in accordance with the PRISMA guidelines. 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 \u2018erectile dysfunction\u2019 and \u2018botulinum toxin\u2019. After screening, 51 studies met the inclusion criteria. Due to significant heterogeneity in interventions (e.g., BoNT-A dosage, co-therapies), patient populations, and reported outcomes, the data were not suitable for meta-analysis. 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 100 U doses. The treatment exhibited a favorable safety profile. The most common adverse event was mild, transient penile pain (reported incidence 1.5\u20136%). 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 their clinical application.<\/jats:p>","DOI":"10.3390\/life15121826","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T09:56:02Z","timestamp":1764323762000},"page":"1826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intracavernosal Botulinum Toxin Injection for Erectile Dysfunction: A Comprehensive Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2425-9795","authenticated-orcid":false,"given":"Vanessa","family":"Talavera Cobo","sequence":"first","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Andres","family":"Yanez Ruiz","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Daniel","family":"Tapia Tapia","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2503-9368","authenticated-orcid":false,"given":"Andres","family":"Calva Lopez","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1175-5706","authenticated-orcid":false,"given":"Carmina Alejandra","family":"Mu\u00f1oz Bastidas","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Marquesado de Santa Marta 2, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-8076","authenticated-orcid":false,"given":"Francisco","family":"Guillen-Grima","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"},{"name":"Biomedical Research Center in Epidemiology and Public Health Network (CIBERESP), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Department of Health Sciences, Public University of Navarra, Av. Bara\u00f1ain, s\/n, 31008 Pamplona, Spain"},{"name":"Group of Clinical Epidemiology, Area of Epidemiology and Public Health, Healthcare Research Institute of Navarre (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Ancizu Marckert","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-4203","authenticated-orcid":false,"given":"Luis","family":"Labairu Huerta","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Torres Roca","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Jose","family":"Diez-Caballero Alonso","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1803-580X","authenticated-orcid":false,"given":"Daniel","family":"Sanchez Zalabardo","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7745-5650","authenticated-orcid":false,"given":"Bernardino","family":"Mi\u00f1ana Lopez","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Marquesado de Santa Marta 2, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-641X","authenticated-orcid":false,"given":"Jose Enrique","family":"Robles Garcia","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra, Av. P\u00edo XII 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"qfaf034","DOI":"10.1093\/sexmed\/qfaf034","article-title":"The effectiveness and safety of intracavernosal botulinum toxin injections in the management of erectile dysfunction: A systematic review and meta-analysis of clinical studies","volume":"13","author":"Pang","year":"2025","journal-title":"Sex. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Giuliano, F., Denys, P., and Joussain, C. (2023). Safety and Effectiveness of Repeated Botulinum Toxin A Intracavernosal Injections in Men with Erectile Dysfunction Unresponsive to Approved Pharmacological Treatments: Real-World Observational Data. Toxins, 15.","DOI":"10.3390\/toxins15060382"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Giuliano, F., Joussain, C., and Denys, P. 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