Estrogen and ischemic neuroproltection: an integrated view

Women are protected from stroke in their early years relative to men. This native neuroprotection is lost within ten years of the menopause, an observation commonly attributed to loss of estrogen with age. Data are now available from large, randomized, clinical trials that question the use of hormone replacement therapy (HRT) for either the primary or secondary prevention of vascular disease and stroke. In contrast to these studies of disease prevention, evidence from the bench suggests that estrogen is a potent neuroprotectant, demonstrating cell salvage from ischemic death pathways. This apparent dichotomy between the limitation of HRT in ameliorating complex disease development vs the excellent performance of estradiol in containing experimental brain damage remains to be understood.