This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Loss of ovarian hormones due to natural or surgical menopause has wide-ranging consequences for women s health and wellbeing. In addition to increasing the risk for cardiovascular disease and osteoporosis, menopause often leads to alterations in cognitive functioning, particularly memory and attention. Hope that these changes will be ameliorated often influences women s choices regarding postmenopausal hormone therapy, but clear evidence is lacking. Conclusive studies in women are difficult because of placebo effects, experimenter and subject bias, sociocultural factors, and ethical considerations. We developed a monkey model of menopause that circumvents these limitations and allows us to examine potential mechanisms of ovarian hormone action in the primate brain. We are conducting a longitudinal study to evaluate effects of surgical menopause (ovariectomy) and subsequent hormone replacement treatment on memory and attention in aging female rhesus monkeys. This study is testing the hypotheses that ovariectomy will impair, that and hormone treatment will restore or improve, cognitive function. The behavioral studies are done in parallel with noninvasive magnetic resonance imaging measures of brain structure to determine whether total brain volume, or the volume of specific cortical areas, are altered by aging and by withdrawal and replacement of ovarian hormones, and whether brain structural parameters are correlated with cognitive performance. These studies provide a controlled test of ovarian hormones effects on brain function in aging females, as well as evidence regarding the underlying brain mechanisms. They will have direct relevance to the difficult and controversial issue of ovarian hormone replacement for menopausal women.
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