Estrogen modulates cognitive and cholinergic processes in surgically menopausal monkeys

Estrogen deficiency in postmenopausal women is associated with changes in physiological processes. The extent to which estrogen loss is associated with cognitive changes noted by postmenopausal women has been more difficult to determine for a variety of reasons. Primate models of menopause are now being used to determine the effects of estrogen loss and replacement on cognitive abilities and to investigate the neural mechanisms by which estrogen may influence cognitive function. The present report presents data from cognitive and neurobiological studies in surgically menopausal monkeys that have examined how estrogen loss and replacement may be affecting cognitive abilities and the cholinergic system; a neural system that is known to influence memory and attention function. These studies are indicating that visuospatial attention function is especially sensitive to estrogen states in young monkeys, but that multiple cognitive domains are sensitive to estrogen states in middle-aged monkeys. In addition, anatomical and functional imaging studies indicate that the primate cholinergic system is modulated by estrogen, and pharmacological studies demonstrate that estrogen uses cholinergic muscarinic receptors to influence visuospatial attention. These studies demonstrate that estrogen influences cognitive abilities in monkey models of menopause and the cholinergic system may be one of the mechanisms by which estrogen modulates cognitive function. Given the current unknowns and concerns regarding the use of hormone replacement therapy in postmenopausal women, continued studies in monkey models of menopause are especially needed to further elucidate the effects of estrogen on cognitive and neurobiological processes, with particular emphasis on studies in middle-aged monkeys, determining the optimal aspects of ERT regimens, and identifying the relationships between estrogen effects on cognitive and neurobiological function.