Results from a retrospective, case-control study presented today at the Society of NeuroInterventional Surgery (SNIS) 7th Annual Meeting could have significant implications for women at risk of brain aneurysms as data shows that oral contraceptives (OC) and hormone replacement therapy (HRT) may yield the additional benefit of protecting against the formation and/or rupture of brain aneurysms – balloon-like sacks that form in a weakened artery wall and, upon bursting, can cause severe disability or death. The study represents one of 130 abstracts submitted to SNIS for consideration for presentation at what has become the premier scientific forum for neurointerventional practitioners, physicians who have innovated minimally invasive techniques to treat various vascular conditions in the brain and spine such as stroke, aneurysms, arteriovenous malformations, and lumbar spinal stenosis.

According to lead author Michael Chen, M.D., Assistant Professor of Neurology, Neurosurgery and Radiology at Rush University Medical Center in Chicago, IL, the study was initiated, in part, due to the observation that in the two largest aneurysm trials to date (the International Subarachnoid Aneurysm Trial released in 2002 and the International Study of Unruptured Intracranial Aneurysms released in 2003), 70 percent of aneurysms occurred in post-menopausal women (mean age of 52), a time of life coinciding with a severe drop in estrogen levels. "By understanding the potential link between low levels of estrogen and aneurysms, we can focus our areas of study with the hope of providing women who are at risk for brain aneurysms with preventative therapies," said Chen.

Generally, risk factors for aneurysm formation and rupture include smoking, hypertension and excessive alcohol use. In earlier animal studies, researchers induced hypertension in 30 female rats that subsequently underwent ovary removal and were assigned to two groups – one-half receiving HRT and one-half not receiving HRT. Of the group that did not receive HRT, 8 out of 15 suffered an aneurysm, but of the group that did receive HRT, only 1 in 15 developed the abnormality. This and other laboratory and clinical studies suggest that the use of OC and HRT, which stabilizes the sudden drop in estrogen during normal menstruation and menopause, can minimize the potential of aneurysms in at-risk women.

Conducted over a two-year period from 2008 to 2010, the Rush study was the first to study a group of women (60) with both unruptured aneurysms (65 percent) and ruptured aneurysms (35 percent). These women ranged in age from 31 to 80, and were under the care of a single physician. By comparing a variety of factors in this case group to that of a control group (from a publicly available data set including 4,682 random female controls who may or may not have had aneurysms), Chen and his team aimed to determine if a link existed between lower estrogen levels and aneurysm incidence. Both groups were screened with questions related to their gynecologic history and the use of estrogen modifying medications. Some of the variables included age of menstrual onset, age at birth of first child, use of OC and HRT and duration, and age of menopause.

In both groups, strong similarities existed across multiple screening factors. The median age of both groups was 53, and when comparing for pertinent criteria, the results were as follows: body mass index, 27.1 for case group and 25.2 for control group; average age of menstrual onset, 13 years for both groups; the incidence for those who never had children, 15 percent for case group and 13 percent for control group; and the incidence for those whose first pregnancy occurred over 30 years of age, 10 percent for case group and 11 percent for control group. Where it concerned use of estrogen modifying agents, however, the results took a notable turn between the two groups. The rate of OC usage was 60 percent for the case group as compared to 77.6 percent for the control group; the rate of HRT usage was 23.7 percent for the case group and 44.8 percent for the control group. Furthermore, when comparing median duration of OC use, results showed 2.6 years for the case group and 5.2 years for the control group.

According to Chen, these differences in the usage of estrogen modifying agents qualify as statistically significant and indicate that women with brain aneurysms not only used OC and HRT less frequently than the general population, but if they did, in the case of OC, it was of shorter duration. It is reasonable to conclude, said Chen, that these results, therefore, support the hypothesis that drops in estrogen that occur in menstruation and particularly at menopause may explain why cerebral aneurysms are more frequently found in women, particularly at menopause.

"For neurointerventional practitioners, this study provides yet another piece of evidence that estrogen stabilization may play a protective role in women who are at risk for brain aneurysms," said Chen. Currently, Chen and his colleagues are designing more studies that will further examine the effects of estrogen on the blood vessels in the brain.