We, and others, have aggressively investigated this question since stroke: (i) is a major form of neurodegeneration

that grossly impacts our aging population, and (ii) has been successfully reproduced in several animal models. To date, most clinical studies have assessed whether ERT alters the risk and mortality of stroke,44 but have not addressed whether estradiol decreases the degree of brain injury LGK-974 molecular weight resulting from stroke. Stroke is a neurodegenerative condition that greatly impacts the health and livelihood of our aging population. It is the third leading cause of death for middleaged and older women, and a major health problem that affects 500 000 Americans Inhibitors,research,lifescience,medical each year.45 Interestingly, premenopausal women are at a lower risk for stroke than men of the same age.46 However, after the menopause the incidence of cerebrovascular disease Inhibitors,research,lifescience,medical rises rapidly.47 These clinical observations parallel statistics on the prevalence of stroke with regard to age and sex: at a younger

age, women appear to be protected Inhibitors,research,lifescience,medical against stroke, compared with men, but lose this advantage in their postmenopausal years (Figure 1).48 Together, these data suggest that endogenous estrogen plays a protective role against stroke. Since stroke imposes major morbidity and mortality in postmenopausal women, it is critical to determine whether ERT may decrease the risk and/or severity of cerebrovascular disease. Figure 1. Endogenous estrogen may decrease the risk for

stroke. Prior to the menopause, women appear to be protected against the occurrence of stroke, compared with age-matched men (left). However, this protection is lost at Inhibitors,research,lifescience,medical some time after the menopause (right), … Classification of stroke Stroke results in infarction of the brain. Major causes and risk factors for stroke include coronary artery disease, cardiac failure, diabetes, hypertension, atherosclerosis, and thrombotic conditions. The overlapping Inhibitors,research,lifescience,medical and often mixed etiologies of stroke can result in two major types of pathology: ischemic stroke or hemorrhagic stroke. Briefly, clot(s) in the cerebro vasculature produce ischemic infarct, and the bursting of cerebral vessel (s) causes subarachnoid hemorrhage. Estrogen and stroke risk Several lines of evidence suggest that ERT may reduce the likelihood for stroke by modifying risk factors that underlie both stroke and coronary heart, disease (CHD).44 Mephenoxalone For example, estrogen may protect by exerting beneficial effects on diabetes and on the scrum lipid profile.49,50 Interestingly, CHD doubles the risk for stroke and ERT greatly reduces the risk for CHD (by 30% to 40%). It thus follows that estrogen may decrease the risk for stroke in parallel with its protective actions on CHD. In contrast to protection, estrogen may, under some circumstances, impose an increased risk for stroke by influencing coagulation and fibrinolysis.