{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:39:12Z","timestamp":1789749552304,"version":"4.0.1"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Background<\/jats:title>\n Female hormone therapy [FHT, birth control treatment and postmenopausal hormone replacement therapy (HRT)] is not withheld from patients with cerebral cavernous malformations (CCM), notwithstanding the uncertainty surrounding the impact of these medications on the risk of intracranial hemorrhage (ICH). This study aimed to evaluate the impact of female hormone therapy on the risk of ICH or focal neurological deficit (FND) in patients with CCM.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The prospective institutional database was examined for all patients with CCM treated at our institution between 2006 and 2023. Inclusion criteria comprised patients with confirmed CCM diagnosis through radiological and\/or histological examination, availability of baseline clinical characteristics, accessible medication history, and follow-up data. Patients were stratified based on their medical treatment regimen, which included female hormone therapy or no treatment. The study assessed the time-to-event probability and the number of events (ICH or FND) during the follow-up period.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 328 female patients with CCM were included in the final analysis. Among them, 56 patients (17.1%) were receiving female hormone therapy. Specifically, 37 patients (11.3%) were using birth control treatments and 19 patients (5.8%) were on HRT. The mean number of ICH per patient was 0.43 (SD 1.11) in the FHT group and 0.38 (SD 0.8) in the control group (\n p<\/jats:italic>\n \u202f=\u202f0.1), while the mean number of FND was 0.36 (SD 0.84) in the FHT group and 0.28 (SD 0.66) in the control group (\n p<\/jats:italic>\n \u202f=\u202f0.58). The time to first ICH was 1631.5\u202fdays (SD 2324.6) in the FHT group and 1161.4\u202fdays (SD 1650.8) in the control group (\n p<\/jats:italic>\n \u202f=\u202f0.35), while the time to first FND was 1601.0\u202fdays (SD 1934.1) in the FHT group and 1208.1\u202fdays (SD 1649.5) in the control group (\n p<\/jats:italic>\n \u202f=\u202f0.86).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The study shows that female patients with a diagnosis of cerebral cavernous malformation receiving female hormone therapy do not experience a significant higher likelihood of intracranial hemorrhage or focal neurological deficit. These findings indicate that, despite the observed tendency, female hormone therapy does not significantly alter the risk of these events in the observed female patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2025.1658980","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:20:55Z","timestamp":1765948855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Female hormone therapy and risk of intracranial hemorrhage and focal neurological deficits in patients with cavernous malformations of the central nervous system"],"prefix":"10.3389","volume":"16","author":[{"given":"Saskia","family":"Wildi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Nager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Staartjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Stumpo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena","family":"\u00d6zkaratufan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklaus","family":"Krayenb\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bozinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Regli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Velz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1161\/STROKEAHA.112.668533","article-title":"Antithrombotic therapy and bleeding risk in a prospective cohort study of patients with cerebral cavernous malformations","volume":"43","author":"Schneble","year":"2012","journal-title":"Stroke"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1016\/j.mayocp.2019.11.005","article-title":"Cerebral cavernous malformation: what a practicing clinician should know","volume":"95","author":"Flemming","year":"2020","journal-title":"Mayo Clin Proc"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s00401-005-0994-8","article-title":"Thrombus and encapsulated hematoma in cerebral cavernous malformations","volume":"109","author":"Abe","year":"2005","journal-title":"Acta Neuropathol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1136\/jnnp.2007.132316","article-title":"Cerebral cavernous malformations: congruency of histopathological features with the current clinical 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contraceptives and HRT risk of thrombosis","volume":"24","author":"Gialeraki","year":"2018","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1001\/archinte.164.18.1965","article-title":"Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy a clinical review","volume":"164","author":"Gomes","year":"2004","journal-title":"Arch Intern Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"E1673","DOI":"10.1212\/WNL.0000000000206888","article-title":"Female hormone therapy and risk of intracranial hemorrhage from cerebral cavernous malformations: a multicenter observational cohort study","volume":"100","author":"Zuurbier","year":"2023","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e342","DOI":"10.1016\/j.wneu.2021.10.092","article-title":"Natural history of brainstem cavernous malformations: on the variation in hemorrhage rates","volume":"157","author":"Yang","year":"2022","journal-title":"World Neurosurg"},{"key":"ref11","volume-title":"Survminer: drawing survival curves using \u201cggplot2\u201d","author":"Kassambara","year":"2021"},{"key":"ref12","volume-title":"Statistics F\u00fcr Bi\u00fcl\u00fcgy and health series editors","author":"Dietz","year":""},{"key":"ref13","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1093\/neuros\/nyx091","article-title":"Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the angioma alliance scientific advisory board clinical experts panel","volume":"80","author":"Akers","year":"2017","journal-title":"Clin Neurosurg"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.3171\/2022.1.JNS212724","article-title":"Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations","volume":"137","author":"Santos","year":"2022","journal-title":"J Neurosurg"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1658980\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:20:56Z","timestamp":1765948856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1658980\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":14,"alternative-id":["10.3389\/fneur.2025.1658980"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1658980","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"article-number":"1658980"}}