Brain aneurysms linked to early onset menopause, study finds

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A correlation between brain aneurysms, bulges or balloons in vessel walls, and early onset menopause has been identified, according to recent study results presented at the Society of NeuroInterventional Surgery (SNIS) 9th Annual Meeting (San Diego, USA, 23–27 July) thereby suggesting that the premature loss of estrogen could be a risk factor for aneurysm formation and development.  

As it is known that the incidence of aneurysm rupture or subarachnoid haemorrhage surges following menopause, a time when estrogen fluctuations are prevalent, these findings may also help define a target population of women for future treatment.

Although the last few decades have introduced better and faster methods of detecting and treating unruptured aneurysms, the incidence of subarachnoid haemorrhage, approximately 30,000 Americans each year, has remained largely unchanged.  Furthermore, mortality rates for ruptured aneurysms continue to average around 50%. “In order to meaningfully reduce the occurrence of eventual aneurysm rupture and bleeding in the brain, it is imperative that the medical community better understand cerebral aneurysms and their disease development and progression,” said Michael Chen, assistant professor of Neurology, Neurosurgery and Radiology, Rush University Medical Center, Chicago, USA and the study author. “Understanding all of the contributing factors to aneurysm development is fundamental to then considering how we approach this disease process. Similar to a puzzle, each individual piece is important to the overall picture.”

Findings resulted from a retrospective, case-control study that compared the gynecologic and medical histories of 76 cases of consecutive postmenopausal women who were diagnosed with brain aneurysms and treated by a single physician from 2009 to 2011 to 532 controls, seven controls for each case, identified in the general population from 1994 to 1998. The only criteria utilised in the control group selection were age and educational level comparable to case subjects. Approximately ten variables were compared between the two groups, including age of menopause onset.

Results showed that 20 of the total cases with brain aneurysms (26.3%) had undergone pre-mature menopause, defined as under age 40, as compared with 102 of the control group (19.2%). When comparing across all variables, later menopause age (OR 0.79, CI 0.63 to 0.996, p1⁄40.046) was significantly associated with a lower aneurysm incidence. Additionally, for each categorical increase in menopause age (40-44, 45-49, 50-54, and greater to or equal to 55), the likelihood of developing a brain aneurysm decreased by 21%. The mean menopause age in both case and control groups showed no significant difference (44.3 and 44.7 respectively).

Beyond findings associating aneurysm incidence and the age of menopause onset, the study also found that the use of hormone replacement therapy (HRT), in 27.6% of the case group as compared with 58.8% of the control group, was significantly associated with lower aneurysm incidence. Together with the correlation between early menopause and the development of brain aneurysms, and existing data that HRT seems to reduce the risk of subarachnoid haemorrhage in post-menopausal women, says Chen, “this finding compels us to consider how to design treatment options, such as HRT, for a specific age spectrum of women with cerebral aneurysms.”

The study was conducted using a custom-designed questionnaire that was provided to all case and control group members. The latter group was selected from profiles of 4,682 women who provided their medical and gynecological histories as part of a federally-funded initiative called the National Institute of Child Health and Human Development-sponsored Contraceptive and Reproductive Experiences Study (CARES), which sought to examine whether any link existed between oral contraceptive pill (OCP) and HRT usage and the risk of developing breast cancer.  Variables compared across the two groups included body mass index, smoking and drinking prevalence, age of menarche onset, number of pregnancies and non-pregnancies, cases of hysterectomy and age of first live birth.

Compared with the control group, the case group showed no statistically significant difference in age, BMI, menarche age, mean age at menopause and percentage of women who had undergone a hysterectomy. In contrast, factors that did demonstrate a statistically significant difference between the two study groups included younger mean age at first live birth (p1⁄40.03), lower percentage of current drinkers (p1⁄40.04) and greater mean number of pack years (p1⁄40.04) in the case group.

According to recent statistics, approximately 6 million people in the USA have an unruptured brain aneurysm, or about one in 50 people. 

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