Background: Intracranial aneurysms (IAs) are more common in females than in males, however, there is still very limited knowledge on sex-dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors and histopathology. Methods: This prospective, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors and histology between sexes. Results: We included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). Three hundred sixty-three patients (36.97%) had multiple IAs, the proportion of which was significantly higher in females. In women, the ICA (40.79%) was the most frequent location for IAs, whereas in men most were found along the ACA territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes, however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex-dependent differences. Histologically, wall-type classification analysis showed significantly more severe aneurysm wall types in men. Conclusion: IA prevalence in women is significantly higher than in men. Women more often present with multiple IAs whereas men were more often diagnosed with ruptured IAs. Sex-specific differences in IA location were identified whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex-dependent manifestations in IAs.

The authors have declared no competing interest.

Funding The author(s) disclosed receipt of the following financial support for the research, and/or publication of this article: T.W. was supported by the OPO Foundation, the Swiss Cancer Research foundation (KFS-3880-02-2016-R, KFS-4758-02-2019-R), the Stiftung zur Krebsbekaempfung, the Kurt und Senta Herrmann Foundation, Forschungskredit of the University of Zurich, the Zurich Cancer League, the Theodor und Ida Herzog Egli Foundation, the Novartis Foundation for Medical-Biological Research and the HOPE Foundation. P.M. was supported by the Canadian Institutes of Health Research. P.B. and B.R.K. were supported by grants from the Swiss SystemsX.ch initiative evaluated by the Swiss National Science Foundation (AneuX), a CONFIRM grant of the Fondation privee des HUG, the Swiss Heart Foundation and the Fondation Carlos et Elsie De Reuter.

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Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration. Written informed consent was obtained from all participants and the HUG had institutional review board approval (@neurIST protocol, ethics authorization PB_2018-00073, previously CCER 07-056). All data were deidentified.

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Data availability Raw data were generated at the Geneva University Hospital. Derived data supporting the findings of this study are available from the corresponding author on request.