Oral Contraceptive and HRT in Women With Cerebral Aneurysms
Oral Contraceptive and HRT in Women With Cerebral Aneurysms
Background It is well known that cerebral aneurysms occur more frequently in women, with numerous studies suggesting a role for hormones in aneurysm pathogenesis. Estrogen promotes normal physiologic vascular endothelial function but also fluctuates during the menstrual cycle and drops significantly at menopause.
Methods A retrospective, case control study was conducted to determine if exogenous estrogen use, which stabilizes estradiol levels, had any association with the presence of cerebral aneurysms. 60 women with intradural cerebral aneurysms were interviewed about their basic medical and female reproductive health histories, including oral contraceptive pill and hormone replacement therapy use and duration of use. This information was compared with the same data 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 Multivariate logistic regression showed a significant association between a lower rate of oral contraceptive (OR 2.1, CI 1.17 to 3.81; p=0.01) and hormone replacement therapy (OR 3.09, CI 1.54 to 6.22; p=0.002) use and the presence of a cerebral aneurysm.
Conclusion These data suggest that exposure to exogenous estrogen agents in women is associated with a lower frequency of cerebral aneurysms.
Each year 30 000 people in the USA develop subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm. When compared with other vascular diseases of the brain, cerebral aneurysms are associated with a unique gender discrepancy.
Multiple studies have reported this consistent gender inequality, including the International Study of Unruptured Intracranial Aneurysms study, which evaluated 4060 patients and found that 75% were women. Similarly, of the 2143 patients in the International Subarachnoid Aneurysm Trial, 63% were women. Another prospective study of aneurysmal SAH found that women have an age adjusted RR of 1.74 compared with men.
Apart from female gender, other well described risk factors associated with cerebral aneurysm rupture include smoking, hypertension, alcohol abuse, low socioeconomic status, autosomal dominant polycystic kidney disease and family history of SAH. A gender related etiology is likely important because many of these risk factors, including hypertension, cigarette smoking and alcohol use, are generally more common in men.
The effects of estrogen on vascular structure and function have been described to occur via its pleiotropic effects on vascular endothelial cells, collagen and nitric oxide. Endothelial cell injury via wall shear stress is considered an initial step in aneurysm formation. The ability of endothelial cells to withstand the wall shear stress from pulsatile arterial blood flow depends on their ability to grow, proliferate and remodel efficiently. Estrogen has been found to contribute to this normal homeostatic process by stimulating endothelial proliferation and reducing vascular tone via its receptors on endothelial and vascular smooth muscle cells. Endothelial remodeling is what leads to maintenance of a constant arterial lumen diameter, which promotes laminar, energy efficient blood flow, in spite of the energy inefficient configuration of the circle of Willis.
As such, changes in estrogen levels may have ramifications on vascular integrity. The estrogen loss that occurs at menopause is well known to be responsible for skin fragility because of its deleterious effects on collagen and elastin. Through similar mechanisms, estrogen loss also leads to diminished elasticity in blood vessels. This may compromise the ability of the vessel wall to effectively remodel to counteract the wall shear stress forces. There may be several clinical correlates to estrogen's effects on the cerebral vasculature. The increase in female prevalence of cerebral aneurysms does not occur until after the age of 40 years. The peak age of incidence of aneurysmal rupture in women is between 50 and 59 years of age while the median age of SAH is around 52 years.
Our aim was to perform a clinical study to characterize the role estrogen plays, if any, in not only the rupture of, but also the pathogenesis of, cerebral aneurysms. Use of exogenous estrogen agents such as oral contraceptive pills (OCP) and hormone replacement therapy (HRT) normalizes the physiologic drops in estrogen seen during the menstrual cycle and particularly at menopause. The goal of this study was to compare the rate of exogenous estrogen use in a cohort of women with largely unruptured cerebral aneurysms, with large sample national averages.
Abstract and Introduction
Abstract
Background It is well known that cerebral aneurysms occur more frequently in women, with numerous studies suggesting a role for hormones in aneurysm pathogenesis. Estrogen promotes normal physiologic vascular endothelial function but also fluctuates during the menstrual cycle and drops significantly at menopause.
Methods A retrospective, case control study was conducted to determine if exogenous estrogen use, which stabilizes estradiol levels, had any association with the presence of cerebral aneurysms. 60 women with intradural cerebral aneurysms were interviewed about their basic medical and female reproductive health histories, including oral contraceptive pill and hormone replacement therapy use and duration of use. This information was compared with the same data 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 Multivariate logistic regression showed a significant association between a lower rate of oral contraceptive (OR 2.1, CI 1.17 to 3.81; p=0.01) and hormone replacement therapy (OR 3.09, CI 1.54 to 6.22; p=0.002) use and the presence of a cerebral aneurysm.
Conclusion These data suggest that exposure to exogenous estrogen agents in women is associated with a lower frequency of cerebral aneurysms.
Introduction
Each year 30 000 people in the USA develop subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm. When compared with other vascular diseases of the brain, cerebral aneurysms are associated with a unique gender discrepancy.
Multiple studies have reported this consistent gender inequality, including the International Study of Unruptured Intracranial Aneurysms study, which evaluated 4060 patients and found that 75% were women. Similarly, of the 2143 patients in the International Subarachnoid Aneurysm Trial, 63% were women. Another prospective study of aneurysmal SAH found that women have an age adjusted RR of 1.74 compared with men.
Apart from female gender, other well described risk factors associated with cerebral aneurysm rupture include smoking, hypertension, alcohol abuse, low socioeconomic status, autosomal dominant polycystic kidney disease and family history of SAH. A gender related etiology is likely important because many of these risk factors, including hypertension, cigarette smoking and alcohol use, are generally more common in men.
The effects of estrogen on vascular structure and function have been described to occur via its pleiotropic effects on vascular endothelial cells, collagen and nitric oxide. Endothelial cell injury via wall shear stress is considered an initial step in aneurysm formation. The ability of endothelial cells to withstand the wall shear stress from pulsatile arterial blood flow depends on their ability to grow, proliferate and remodel efficiently. Estrogen has been found to contribute to this normal homeostatic process by stimulating endothelial proliferation and reducing vascular tone via its receptors on endothelial and vascular smooth muscle cells. Endothelial remodeling is what leads to maintenance of a constant arterial lumen diameter, which promotes laminar, energy efficient blood flow, in spite of the energy inefficient configuration of the circle of Willis.
As such, changes in estrogen levels may have ramifications on vascular integrity. The estrogen loss that occurs at menopause is well known to be responsible for skin fragility because of its deleterious effects on collagen and elastin. Through similar mechanisms, estrogen loss also leads to diminished elasticity in blood vessels. This may compromise the ability of the vessel wall to effectively remodel to counteract the wall shear stress forces. There may be several clinical correlates to estrogen's effects on the cerebral vasculature. The increase in female prevalence of cerebral aneurysms does not occur until after the age of 40 years. The peak age of incidence of aneurysmal rupture in women is between 50 and 59 years of age while the median age of SAH is around 52 years.
Our aim was to perform a clinical study to characterize the role estrogen plays, if any, in not only the rupture of, but also the pathogenesis of, cerebral aneurysms. Use of exogenous estrogen agents such as oral contraceptive pills (OCP) and hormone replacement therapy (HRT) normalizes the physiologic drops in estrogen seen during the menstrual cycle and particularly at menopause. The goal of this study was to compare the rate of exogenous estrogen use in a cohort of women with largely unruptured cerebral aneurysms, with large sample national averages.
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