Neuroprotective actions of estradiol revisited.

Results from animal experiments showing that estradiol is neuroprotective were challenged 10 years ago by findings indicating an increased risk of dementia and stroke in women over 65 years of age taking conjugated equine estrogens. Our understanding of the complex signaling of estradiol in neural cells has recently clarified the causes of this discrepancy. New data indicate that estradiol may lose its neuroprotective activity or even increase neural damage, a situation that depends on the duration of ovarian hormone deprivation and on age-associated modifications in the levels of other molecules that modulate estradiol action. These studies highlight the complex neuroprotective mechanisms of estradiol and suggest a window of opportunity during which effective hormonal therapy could promote brain function and cognition.