Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause.

Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes.

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.

Effects of two years of estrogen loss or replacement on nucleus basalis cholinergic neurons and cholinergic fibers to the dorsolateral prefrontal and inferior parietal cortex of monkeys.

The present study examined the long-term (2 years) effects of estrogen loss or estrogen replacement therapy (ERT) on cholinergic neurons in the nucleus basalis of Meynert and on cholinergic fibers in the prefrontal and parietal cortex of adult female cynomolgus monkeys. Cholinergic fiber density in layer II of the prefrontal cortex was decreased in monkeys who were ovariectomized and treated with placebo for 2 years. In contrast, ovariectomized monkeys receiving ERT for 2 years had fiber densities that were comparable to those of intact controls.