Stroke and the Female Brain

Cheryl D Bushnell


Nat Clin Pract Neurol. 2008;4(1):22-33. 

In This Article

Summary and Introduction

Stroke is a major public health problem. The female population carries a higher stroke burden than the male population, both because females have a longer life expectancy and because most stroke deaths occur in women. Differences between the sexes in relation to stroke are increasingly being recognized; for example, among stroke survivors, women tend to have worse outcomes than men, as indicated by more-severe disability and an increased likelihood of institutionalization in women. Women and men with stroke also differ in their risk factor profiles, and they respond differently to primary-prevention and acute stroke treatment. Women experience variations in endogenous estrogens throughout their life cycle and might also be exposed to exogenous estrogens, both of which markedly affect the brain. An understanding of the effects of endogenous and exogenous estrogens on cerebral hemodynamics could guide research into explaining how hormone therapy increases the risk of stroke in postmenopausal women. This Review summarizes the sex differences related to stroke, and the effect of endogenous and exogenous hormones on the cerebrovasculature of the female brain. It also proposes potential research approaches, the results of which could fill in gaps in our knowledge regarding the mechanism of action of estrogen in the brain.

Each year, around 700,000 Americans experience a stroke, incurring a total estimated annual cost of $58 billion.[1] Stroke is the third leading cause of death in most countries, and is one of the leading causes of long-term disability.[1] Women have a higher lifetime risk of stroke than men (1 in 5 vs 1 in 6), a statistic that is influenced in part by the longer life expectancy in women.[2] The female population not only carries a higher burden of stroke during their lifespan -- women also account for the majority of stroke deaths.[1] Men typically have a higher incidence of stroke than women up to the age of 75 years, when the incidence in women becomes higher.[1] New data, however, indicate that the incidence of stroke in women in the mid-life years might be increasing. Data from a cohort that was studied from 1999 to 2004 indicated that women aged 45-54 years were around twice as likely to have a stroke as men of the same age.[3] One potential explanation for this finding is that women in this age stratum are transitioning to menopause, a time when cardiovascular risk factors appear or existing risk factors worsen.[4] The incidence of stroke in women might, therefore, be increasing because stroke risk factors go unrecognized or are inadequately treated. Given this surge in stroke prevalence in mid-life women, and the likelihood that stroke risk will continue to increase as women age, from a public health perspective it is critically important to focus research efforts on understanding stroke in women. The purpose of this Review is to further elucidate sex differences in stroke, to describe the unique risks and benefits of estrogens on the female brain, and to propose future directions of research that might find ways to decrease the burden of stroke in women.


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