Gender differences and the effects of synthetic exogenous and non-synthetic estrogens in focal cerebral ischemia

The role of gender difference and estrogen in ischemic cerebrovascular events is controversial. Evidence is lacking as to whether or not there are significant gender differences in the incidence and outcome of stroke in the clinical setting. Recent clinical epidemiological studies have demonstrated that there is no significant association between the use of hormonal replacement therapy and the risk of stroke. However, several animal studies have shown that there are gender differences in stroke outcome and that exogenous administered estrogens are neuroprotective. In this study, the influence of gender differences and the effects of synthetic and non-synthetic estrogens were examined in a model of focal cerebral ischemia using 210 male, intact female, and ovariectomized female rats. All animals underwent 3 h of middle cerebral artery and bilateral common carotid artery occlusion. After 72 h, the rats were sacrificed and stained for histological assessment of infarction. There were no gender differences in infarction volume. Intravenous administration of either low or high dose 17β-estradiol or tibolone did not alter infarct volume. Subcutaneous administration of low and high dose 17β-estradiol using 7-day release pellets did not alter infarct volume. Low dose tibolone using implanted 7-day release pellets did not alter infarct volume. However, high dose tibolone using implanted 7-day release pellets significantly (P < 0.05) reduced infarct volume only in ovariectomized female rats. These results demonstrate that estrogen therapy has no effect on infarction volume following severe focal cerebral ischemia.