ABSTRACT
Use of estrogen therapy in the perimenopausal and postmenopausal periods has been
shown in several clinical trials to help women maintain a premenopausal level of cognitive
function. What is not yet fully understood is how the neurobiological effects of estrogen
contribute to these cognitive effects. This review explores data from two related
bodies of human literature that provide compelling evidence in support of the biological
plausibility that estrogen treatment can benefit cognition. The first half of the
literature review focuses on studies from the estrogen neuroimaging literature, and
the second half focuses on pharmacologic challenge studies assessing estrogen-neurotransmitter
interactions. We integrate these two bodies of literature by focusing on the neurophysiologic
underpinnings of estrogen effects on cognition and linking these clinical studies
to preclinical studies. The focus on verbal memory is important because it is a cognitive
function that has been shown to change with estrogen treatment and predict Alzheimer's
disease risk but is not addressed by preclinical studies. Overall, we conclude that
estrogen interacts with cholinergic and serotonergic systems to affect hippocampal
and frontal cortical brain areas and thereby enhance memory, particularly at the retrieval
stage.
KEYWORDS
Estrogen - brain - cognition - psychopharmacology - neuroimaging
REFERENCES
pmaki@psych.uic.edu
