Background and purpose Although ruptured cerebral aneurysms are more common in postmenopausal women than in premenopausal women, or men, the putative hormonal role that underlies this disparity is poorly understood. Prior clinical and laboratory studies suggest that estrogen, via multiple mechanisms, is critical in maintaining arterial vascular integrity and tone. Use of oral contraceptives (OCP) and hormone replacement therapy (HRT) attenuates the sudden physiologic drops in estrogen seen during the normal menstrual cycle and at menopause. The goal of this study was to compare the rate of exogenous estrogen modifying agent use in a cohort of women with cerebral aneurysms with large sample national averages.

Methods With IRB approval, a retrospective, case control study was performed via trained telephone interviews at a US urban tertiary center. Female patients with cerebral aneurysms under the care of a single physician (MC) from over a 2 year period were compared with a publically available data set from 4682 random female controls in the US, also interviewed via telephone using random digit dialing (Ann Epidemiol 2002;12:213–22). The questions asked of both groups were similar with regard to gynecologic history and the use and duration of estrogen modifying medications. Variables included age of menarche, parity, age at birth of first child, use of oral contraceptives and duration if any, use of HRT and duration if any, and age at menopause. Univariate and multivariate analyses were performed.

Results Between 2008 and 2009, 49 cases were successfully interviewed with an age range between 31 and 80 years. χ² tests of independence were performed to examine the relationship between OCPs or HRTs in cases compared with controls. The lower rate of OCP (χ² (1, N=)=0, p<0.0001) and HRT (χ² (1, N=)=0, p=0.0292) use among cases was statistically significant. Furthermore, an independent samples t test showed a statistically significant lower mean duration of OCP among cases compared with controls (p=0.0041).

Conclusions Women with cerebral aneurysms not only used OCP and HRT less frequently than the general population but if they did it was of shorter duration. These results support the hypothesis that physiologic drops in estrogen that occur during the menstrual cycle and particularly at menopause may explain why cerebral aneurysms are more frequently found in women, particularly during menopause. A protective role for pharmacologic estrogen stabilization in women who are at risk for cerebral aneurysm formation warrants further study.