Female hormonal and reproductive factors and the risk of subarachnoid hemorrhage

Background: Subarachnoid hemorrhage (SAH), primarily caused by rupture of intracranial aneurysm, has a high incidence rate in women. We aimed to evaluate the association between female hormonal and reproductive factors and SAH. Methods: A prospective cohort of 226,469 participants from the UK Biobank was followed for a median period of 14.75 years. Cox proportional hazards models and restricted cubic splines were used to explore the associations between 13 major factors and SAH, including menarche age, menopausal status, age at menopause, reproductive lifespan, pregnancy history, age at first and last live births, number of live births, adverse fertility outcomes, history of oral contraception or hormone-replacement therapy (HRT) use, and surgical history of hysterectomy or bilateral oophorectomy. Results: SAH occurred in 769 of participants during the follow-up period. Both women with a younger age at menarche (< 12 years) and post-menopausal women had a higher SAH risk (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.06-1.54) and (HR, 1.48; 95% CI, 1.10-1.99), respectively. A higher risk of SAH was identified in those with an earlier age at menopause (< 40 years: HR, 2.09; 95% CI, 1.43-3.06; 40-44 years: HR, 1.68; 95% CI, 1.23-2.29). A shorter reproductive lifespan (< 30 years) was associated with increased SAH risk (HR, 1.64; 95% CI, 1.28-2.11), while a longer reproductive lifespan (> 42 years) showed a protective effect (HR, 0.65; 95% CI, 0.55-0.77). Younger age at first live birth (< 24 years) was associated with SAH (HR, 1.39; 95% CI, 1.13-1.72). Hysterectomy (HR, 2.55; 95% CI, 2.12-3.05) or bilateral oophorectomy (HR, 1.51; 95% CI, 1.14-2.01) also predisposed women to SAH. Age at last live birth, number of live births, pregnancy history, adverse fertility outcomes, and HRT or oral contraceptive use were not associated with SAH. Conclusions: Female hormonal and reproductive factors are important for evaluating SAH risk in women. In particular, earlier menopause is associated with an increased risk of SAH. Data access statement: The data utilized in this study were sourced from a third party and are not publicly accessible. The UK Biobank data that support the findings of this research are available from the UK Biobank (www.ukbiobank.ac.uk), subject to review and approval by the UK Biobank.