The women's health initiative estrogen replacement therapy is neurotrophicand neuroprotective

The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United Stares and the estrogen replacement therapy of the Women's Health Initiative. Morphol ogic analyses demonstrated that CEEs significantly increased neuronal outgr owth in hippocampal, basal forebrain, occipital, parietal and frontal corte x neurons. Dose-response analyses indicated that the lowest effective conce ntration of CEEs exerted the maximal neurotrophic effect with greatest pote ncy occurring in hippocampal and occipital cortex neurons. GEES induced hig hly significant neuroprotection against beta amyloid(25-35), hydrogen perox ide and glutamate-induced toxicity. Rank order of potency and magnitude of GEE-induced neuroprotection in the brain regions investigated was hippocamp al neurons > basal forebrain neurons > cortical neurons. In hippocampal neu rons pre-exposed to beta amyloid(25-35), CEEs halted A beta(25-35)-induced cell death and protected surviving neurons fi om further cell death induced by A beta(25-35). Because CEEs are the estrogen-replacement therapy of the Women's Health Initiative, results of the current study could provide cell ular mechanisms for understanding effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial. (C) 2000 Elsevier Science Inc. All rights: reserved.