The influence of reproductive hormones on brain function in the menopausal transition.

Reproductive hormones have long been thought to have a significant impact on brain function in humans. Estrogens, progestins and androgens have all been shown to have effects on nerve growth and function in vitro. The neurofunctional domains of cognition, mood and sleep are now receiving increased study to determine both the relationship of endogenous sex steroids through the menopausal transition and the effect of menopausal hormone therapy on these complex functions. All three domains are the source of frequent concern in midlife women, but the relative contribution of ovarian versus somatic aging is only now being untangled. Cognitive function has been most extensively studied, with mixed results in both observational studies and clinical trials, largely due to the remarkably complex aspects of human cognition requiring extensive and targeted testing of specific components. Both mood and sleep disorders have been associated with the menopausal transition, but observed effects appear modest. To date, clinical trial data are insufficient to support the use of hormone therapy specifically for the prevention or treatment of cognitive, mood or sleep disorders in midlife women.