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Published Online:https://doi.org/10.1176/ajp.154.12.1641

OBJECTIVE: The goal of this overview is to examine male/female differences in psychopathology in light of the known effects of gonadal steroids, especially estradiol, on neural function. METHOD: The epidemiology of specific psychopathological syndromes is highlighted with respect to male/female differences and discussed against the backdrop of recent neuroendocrine findings. RESULTS: A number of differences between the sexes in rates of illness and course of illness are documented, with Alzheimer's disease, schizophrenia, alcoholism, and mood and anxiety disorders each illustrating slightly different hormone-mediated risks and buffers. CONCLUSIONS: Estrogens are neuroprotective with respect to neuronal degeneration, growth, and susceptibility to toxins. The cyclic fluctuations of estrogens and progesterone enhance the response to stress, which confers susceptibility to depression and anxiety. (Am J Psychiatry 1997; 154:1641–1647)