Background The incidence of subarachnoid hemorrhage in women surges following menopause. Estrogen fluctuations have been implicated in cerebral aneurysm formation, growth and rupture and is thought to explain the well known gender disparity. The aim of this study was to examine the association between age at menopause, which can determine lifetime estrogen exposure, and the presence of cerebral aneurysms.

Methods We conducted a retrospective, case–control study by interviewing postmenopausal women with intradural cerebral aneurysms about their basic medical and gynecologic histories. This information was compared with the same data points collected from women in the general public, as represented by 4682 women contacted through random digit phone dialing in the National Institute of Child Health and Human Development sponsored Contraceptive and Reproductive Experiences Study, published in 2002.

Results Among 76 consecutive postmenopausal women with cerebral aneurysms who were treated by a single physician and interviewed, multivariate logistic regression showed that both later menopause age (OR 0.79, 95% CI 0.63 to 0.996, p=0.046) and ever use of hormone replacement therapy (OR 0.23, 95% CI 0.13 to 0.42, p<0.0001) were significantly associated with a lower aneurysm incidence. Premature menopause (<40 years) was seen in 26% of cases and 19% of controls (p=0.15). Each categorical increase in menopause age (<40, 40–44, 45–49, 50–54, ≥55) decreased the likelihood by 21%. Despite a trend toward earlier mean age at menopause in the case group, the difference was not statistically significant.

Conclusion There is a trend showing an earlier age at menopause to be associated with the presence of a cerebral aneurysm. This suggests that loss of estrogen earlier in a woman's life may contribute to cerebral aneurysm pathogenesis. Growing evidence has suggested the importance of the “timing hypothesis” when determining whether HRT will be beneficial in post-menopausal women. This data may not only identify a risk factor for cerebral aneurysm pathogenesis, but also identify a potential target for future therapies.

Competing interests None.