{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:00:51Z","timestamp":1791396051010,"version":"4.3.3"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erectile dysfunction (ED) is a prevalent and burdensome condition. Intracavernosal botulinum toxin type A (BoNT-A) has been investigated as an alternative for refractory patients to standard therapies; however, the methodological quality and degree of primary study overlap across published systematic reviews remain uncharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To synthesize evidence on the efficacy and safety of intracavernosal BoNT-A for ED, and to evaluate methodological quality, risk of bias, primary study overlap, and certainty of evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This umbrella review was conducted according to a predefined protocol and reported in accordance with Preferred Reporting Items for Overviews of Reviews 2022 statement. PubMed (MEDLINE), Web of Science, Scopus, Cochrane Library, Epistemonikos, and LILACS were searched from inception to January 2026. Google Scholar was additionally searched. Eligible studies were systematic reviews evaluating intracavernosal BoNT-A for ED. Methodological quality was assessed with AMSTAR-2, review-level risk of bias with Risk of Bias in Systematic Reviews (ROBIS), primary study overlap with the corrected covered area (CCA), and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four systematic reviews were included, encompassing 10 unique ED-specific primary studies (n\u2009=\u2009865). The CCA was 53.3%, indicating very high overlap. Three reviews were rated critically low and one as low confidence by AMSTAR-2. All four reviews were judged to be at high overall risk of bias using ROBIS. Improvements in erectile function were consistently reported across reviews; however, substantial heterogeneity precluded robust quantitative synthesis. GRADE certainty of evidence was low for erectile function improvement and short-term safety, and very low for response rate and long-term safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although some systematic reviews included in this umbrella review reported improvements in erectile function following intracavernosal BoNT-A, the overall certainty of evidence is low to very low across all pre-specified outcomes. Substantial heterogeneity, very high primary study overlap, and methodological shortcomings in available reviews substantially limit the ability to draw firm conclusions regarding its clinical use. Rigorous randomized trials with standardized protocols are required before this intervention can be considered for clinical adoption.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdag311","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:24:20Z","timestamp":1789755860000},"source":"Crossref","is-referenced-by-count":0,"title":["Intracavernosal botulinum toxin type A in refractory erectile dysfunction: umbrella review with GRADE certainty assessment and corrected covered area analysis"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2425-9795","authenticated-orcid":false,"given":"Vanessa Talavera","family":"Cobo","sequence":"first","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Andr\u00e9s","family":"Y\u00e1nez Ruiz","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["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 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Calva L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Royo Taberner","sequence":"additional","affiliation":[{"name":"Science Library, University of Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"S\u00e1nchez Zalabardo","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardino","family":"Mi\u00f1ana Lopez","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Marquesado de Santa Marta 2, 28027 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Enrique","family":"Robles Garcia","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinica Universidad de Navarra , Av. P\u00edo XII 36, 31008 Pamplona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"issue":"1","key":"2026100713340411900_ref1","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1186\/s12889-024-20300-7","article-title":"The global burden of erectile dysfunction and its associated risk factors in diabetic patients: an umbrella review","volume":"24","author":"Kitaw","year":"2024","journal-title":"BMC Public Health"},{"issue":"1","key":"2026100713340411900_ref2","doi-asserted-by":"publisher","first-page":"27374","DOI":"10.1038\/s41598-024-78607-9","article-title":"Comparison of economic burden of disease and quality of life in patients with premature ejaculation and erectile dysfunction","volume":"14","author":"Fu","year":"2024","journal-title":"Sci Rep"},{"key":"2026100713340411900_ref3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2147\/RRU.S283097","article-title":"The quality of life and economic burden of erectile dysfunction","volume":"13","author":"Elterman","year":"2021","journal-title":"Res Rep Urol"},{"issue":"1","key":"2026100713340411900_ref4","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/nrurol.2017.161","article-title":"PDE5 inhibitors \u2014 pharmacology and clinical applications","volume":"14","author":"Andersson","year":"2018","journal-title":"Nat Rev Urol"},{"issue":"3","key":"2026100713340411900_ref5","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.eururo.2021.06.007","article-title":"European Association of Urology guidelines on sexual and reproductive health: erectile dysfunction","volume":"80","author":"Salonia","year":"2021","journal-title":"Eur Urol"},{"issue":"6","key":"2026100713340411900_ref6","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s00345-019-02727-5","article-title":"Erectile dysfunction: a global review of intracavernosal injectables","volume":"37","author":"Duncan","year":"2019","journal-title":"World J Urol"},{"issue":"9","key":"2026100713340411900_ref7","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/medsci7090091","article-title":"A review of current and emerging therapeutic options for erectile dysfunction","volume":"7","author":"Chung","year":"2019","journal-title":"Med Sci (Basel)"},{"issue":"3","key":"2026100713340411900_ref8","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1093\/sxmrev\/qead014","article-title":"An overview of the history, current strategies, and potential future treatment approaches in erectile dysfunction","volume":"11","author":"Langarizadeh","year":"2023","journal-title":"Sex Med Rev"},{"issue":"5","key":"2026100713340411900_ref9","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.3390\/cells9051250","article-title":"Revisiting the regenerative therapeutic advances towards erectile dysfunction","volume":"9","author":"Liu","year":"2020","journal-title":"Cells."},{"issue":"1","key":"2026100713340411900_ref10","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5534\/wjmh.200007","article-title":"Novel emerging therapies for erectile dysfunction","volume":"39","author":"Kim","year":"2021","journal-title":"World J Mens Health"},{"issue":"5","key":"2026100713340411900_ref11","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3390\/toxins11050283","article-title":"Safety and efficacy of intracavernosal injections of abobotulinumtoxinA (Dysport\u00ae) as add-on therapy to PDE5i or PGE1 for erectile dysfunction: case studies","volume":"11","author":"Giuliano","year":"2019","journal-title":"Toxins (Basel)"},{"issue":"6","key":"2026100713340411900_ref12","doi-asserted-by":"publisher","first-page":"382","DOI":"10.3390\/toxins15060382","article-title":"Safety and effectiveness of repeated intracavernosal botulinum toxin a injections in men with erectile dysfunction unresponsive to approved pharmacological treatments: real-world observational data","volume":"15","author":"Giuliano","year":"2023","journal-title":"Toxins (Basel)"},{"issue":"11","key":"2026100713340411900_ref13","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1093\/jsxmed\/qdaf225","article-title":"Multicenter, randomized, double-blind, placebo-controlled trial of intracavernosal onabotulinumtoxinA for erectile dysfunction","volume":"22","author":"Giuliano","year":"2025","journal-title":"J Sex Med"},{"issue":"6","key":"2026100713340411900_ref14","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.jsxm.2022.03.213","article-title":"Intracavernosal onabotulinumtoxinA exerts a synergistic pro-erectile effect when combined with sildenafil in spontaneously hypertensive rats","volume":"19","author":"Giuliano","year":"2022","journal-title":"J Sex Med"},{"issue":"4","key":"2026100713340411900_ref15","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1111\/andr.13010","article-title":"Intra-cavernous injection of BOTOX\u00ae (50 and 100 units) for treatment of vasculogenic erectile dysfunction: randomized controlled trial","volume":"9","author":"El-Shaer","year":"2021","journal-title":"Andrology."},{"issue":"2","key":"2026100713340411900_ref16","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1111\/andr.13104","article-title":"Safety and efficacy of botulinum neurotoxin in the treatment of erectile dysfunction refractory to phosphodiesterase inhibitors: results of a randomized controlled trial","volume":"10","author":"Abdelrahman","year":"2022","journal-title":"Andrology."},{"issue":"7","key":"2026100713340411900_ref17","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.jsxm.2022.03.216","article-title":"Botox for erectile dysfunction","volume":"19","author":"Habashy","year":"2022","journal-title":"J Sex Med"},{"key":"2026100713340411900_ref18","doi-asserted-by":"publisher","first-page":"e070849","DOI":"10.1136\/bmj-2022-070849","article-title":"Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement","volume":"378","author":"Gates","year":"2022","journal-title":"BMJ."},{"issue":"9","key":"2026100713340411900_ref19","doi-asserted-by":"publisher","first-page":"e0138237","DOI":"10.1371\/journal.pone.0138237","article-title":"The role of Google scholar in evidence reviews and its applicability to grey literature searching","volume":"10","author":"Haddaway","year":"2015","journal-title":"PLoS One"},{"key":"2026100713340411900_ref20","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ."},{"issue":"4","key":"2026100713340411900_ref21","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.jclinepi.2013.11.007","article-title":"Systematic review finds overlapping reviews were not mentioned in every other overview","volume":"67","author":"Pieper","year":"2014","journal-title":"J Clin Epidemiol"},{"issue":"7650","key":"2026100713340411900_ref22","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE working group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ."},{"issue":"5","key":"2026100713340411900_ref23","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/j.eururo.2011.07.053","article-title":"Minimal clinically important differences in the erectile function domain of the international index of erectile function scale","volume":"60","author":"Rosen","year":"2011","journal-title":"Eur Urol"},{"issue":"6","key":"2026100713340411900_ref24","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1111\/j.1743-6109.2007.00600.x","article-title":"Validation of the erection hardness score","volume":"4","author":"Mulhall","year":"2007","journal-title":"J Sex Med"},{"key":"2026100713340411900_ref25","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.urology.2022.08.039","article-title":"Intracavernosal injection of botulinum toxin in the treatment of erectile dysfunction: a systematic review and meta-analysis","volume":"170","author":"Zahr","year":"2022","journal-title":"Urology."},{"key":"2026100713340411900_ref26","doi-asserted-by":"publisher","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"},{"issue":"6","key":"2026100713340411900_ref27","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1111\/andr.70142","article-title":"A systematic review on administration of botulinum toxin in male sexual dysfunctions","volume":"14","author":"Henriques","year":"2025","journal-title":"Andrology."},{"issue":"12","key":"2026100713340411900_ref28","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.3390\/life15121826","article-title":"Intracavernosal botulinum toxin injection for erectile dysfunction: a comprehensive systematic review","volume":"15","author":"Talavera Cobo","year":"2025","journal-title":"Life (Basel)"},{"issue":"2","key":"2026100713340411900_ref29","doi-asserted-by":"publisher","first-page":"259","DOI":"10.5534\/wjmh.240123","article-title":"Clinical effects and safety outcomes of platelet-rich plasma therapy in patients with vasculogenic erectile dysfunction: a systematic review and meta-analysis","volume":"43","author":"Falcone","year":"2025","journal-title":"World J Mens Health"},{"issue":"1","key":"2026100713340411900_ref30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jsxm.2016.11.001","article-title":"Effects of low-intensity extracorporeal shockwave therapy on erectile dysfunction: a systematic review and meta-analysis","volume":"14","author":"Clavijo","year":"2017","journal-title":"J Sex Med"},{"issue":"1","key":"2026100713340411900_ref31","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jsxm.2021.10.011","article-title":"Long-term effectiveness and safety of intracavernosal botulinum toxin a as an add-on therapy to PDE5i or PGE1 injections for erectile dysfunction","volume":"19","author":"Giuliano","year":"2022","journal-title":"J Sex Med"},{"issue":"2","key":"2026100713340411900_ref32","doi-asserted-by":"publisher","first-page":"949","DOI":"10.21037\/tau.2020.02.09","article-title":"Practical approaches to treat erectile dysfunction in PDE5 inhibitor non-responders","volume":"9","author":"Cai","year":"2020","journal-title":"Transl Androl Urol"},{"key":"2026100713340411900_ref33","doi-asserted-by":"publisher","first-page":"e119131","DOI":"10.5812\/numonthly.119131","article-title":"Efficacy of intracavernosal injections of 50-unit versus 100-unit doses of abobotulinumtoxinA in vasculogenic erectile dysfunction with PDE5i resistance","volume":"14","author":"Moradi","year":"2022","journal-title":"Nephrourol Mon"},{"key":"2026100713340411900_ref34","doi-asserted-by":"publisher","first-page":"31","DOI":"10.21608\/bjas.2019.186903","article-title":"Comparative study between intracavernosal injection of botulinum toxin type a (50 and 100 units), efficacy and durability in the treatment of vascular erectile dysfunction","volume":"4","author":"Taleb","year":"2019","journal-title":"Benha J Appl Sci"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/23\/11\/qdag311\/71667235\/qdag311.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/23\/11\/qdag311\/71667235\/qdag311.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:34:07Z","timestamp":1791394447000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/doi\/10.1093\/jsxmed\/qdag311\/8875959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1093\/jsxmed\/qdag311","relation":{},"ISSN":["1743-6095","1743-6109"],"issn-type":[{"value":"1743-6095","type":"print"},{"value":"1743-6109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,11]]},"published":{"date-parts":[[2026,10,7]]},"article-number":"qdag311"}}