Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Objective: The incidence of subarachnoid hemorrhage (SAH) increases after menopause. Anecdotal data suggest that hormone replacement therapy (HRT) may reduce the rate of SAH and aneurysm formation in women. The goal of this study was to determine the effect of HRT on occurrence of SAH in a large prospective cohort of postmenopausal women. Methods: The data were analyzed for 93,676 women 50-79 years of age who were enrolled in the observational arm of the Women's Health Initiative Study. The effect of HRT on risk of SAH was determined over a period of 12 ± 1 years (mean ± SD) using Cox proportional hazards analysis after adjusting for potential confounders. Additional analysis was performed to identify the risk associated with "estrogen only" and "estrogen and progesterone" HRT among women. Results: Of the 93,676 participants, 114 (0.1%) developed SAH during the follow-up period. The rate of SAH was higher among women on active HRT compared with those without HRT used (0.14% vs 0.11%, absolute difference 0.03%, p < 0.0001). In unadjusted analysis, participants who reported active use of HRT were 60% more likely to suffer an SAH (RR 1.6, 95% CI 1.1-2.3). Compared with women without HRT use, the risk of SAH continued to be higher among women reporting active use of HRT (RR 1.5, 95% CI 1.0-2.2) after adjusting for age, systolic blood pressure, cigarette smoking, alcohol consumption, body mass index, race/ethnicity, diabetes, and cardiovascular disease. The risk of SAH was nonsignificantly higher among women on "estrogen only" HRT (RR 1.4, 95% CI 0.91-2.0) than "estrogen and progesterone" HRT (RR 1.2, 95% CI 0.8-2.1) after adjusting for the above-mentioned confounders. Conclusions: Postmenopausal women, particularly those at risk for SAH due to presence of unruptured aneurysms, family history, or cardiovascular risk factors, should be counseled against use of HRT.