Estrogen as a neuroprotectant in stroke

Recent evidence suggests that reproductive steroids are important players i n shaping stroke outcome and cerebrovascular pathophysiologic features. Alt hough women are at lower risk for stroke than men, this native protection i s lost in the postmenopausal years. Therefore, aging women sustain a large burden for stroke, contrary to a popular misconception that cancer is the m ain killer of women. Further, the value of hormone replacement therapy in s troke prevention or in improving outcome remains controversial. Estrogen ha s been the best studied of the sex steroids in both laboratory and clinical settings and is considered increasingly to be an endogenous neuroprotectiv e agent. A growing number of studies demonstrate that exogenous estradiol r educes tissue damage resulting from experimental ischemic stroke in both se xes. This new concept suggests that dissecting interactions between estroge n and cerebral ischemia will yield novel insights into generalized cellular mechanisms of injury. Less is known about estrogen's undesirable effects i n brain, for example, the potential for increasing seizure susceptibility a nd migraine. This review summarizes gender-specific aspects of clinical and experimental stroke and results of estrogen treatment on outcome in animal models of cerebral ischemia, and briefly discusses potential vascular and parenchymal mechanisms by which estrogen salvages brain.