Today, there is a large body of evidence suggesting a protective effect of estrogen in a variety of experimental models of stroke. Studies of focal as well as global brain ischemia in various rodent models have consistently shown that female animals sustain less tissue damage than males after similar insults.5-8 This beneficial effect of female gender is lost in reproductively senescent animals7 or after ovariectomy but can be restored by estrogen supplementation.7, 9-11 Estrogen treatment proved similarly beneficial in male animals.12-14 Although most of these animal studies emphasized infarct size and cell loss early after the insult, chronic estrogen supplementation also improved functional outcome.15,16 The effects of chronic estrogen exposure in these models may explain some of the female advantage in IBI, and they are the focus of recent studies in primary stroke prevention. However, since long-term treatment before a perioperative brain insult is obviously not an option for neuroprotection, the efficacy of acute treatment with estrogen in the perioperative setting at or after onset of ischemia has also been tested in experimental ischemia and found to reduce brain damage.17,18 This benefit also extends to male animals.12