Introduction

Research over the past 30 years has demonstrated that the brain is an important target organ for estrogen effects. Studies using sensitive autoradiographic and immunohistochemical techniques have documented the presence of estrogen receptors throughout the brain (Brown et al., 1995; Österlund et al., 1998; Pfaff, 1968; Rainbow et al., 1982). The highest levels of receptors are often detected in brain areas involved in gonadal regulation, physiologic homeostasis, and reproductive behavior. Receptors have also been detected throughout the neocortex, hippocampus, and amygdala – regions of the brain long known to be associated with higher cognitive functions such as learning, memory, and attention. Some of the effects of estrogen recently described include changes in neurotransmitter production and release, changes in the number and frequency of synaptic contacts, and changes in the expression and regulation of second messengers and transcription factors, as well as effects on cell survival and growth.

Given the variety of estrogen effects throughout the brain, it is not surprising that estrogen should affect cognitive processes or that the loss of estrogen would play a role in the biology of brain aging in women. Consider that women in the United States reach menopause at approximately 51 years of age, and that the average lifespan for women in the United States is 79 years. This means that approximately 28 years of a woman's life are postmenopausal and reflect a hypoestrogenic state.