COGNITION AND ESTROGEN IN MIDDLE-AGED FEMALE MONKEYS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。由于自然或手术绝经而导致的卵巢激素损失对女性的健康和福祉有广泛的影响。除了增加患心血管疾病和骨质疏松症的风险外，更年期还经常导致认知功能的改变，特别是记忆力和注意力。希望这些变化得到改善往往会影响妇女对绝经后激素治疗的选择，但缺乏明确的证据。由于安慰剂效应、实验者和受试者的偏见、社会文化因素和伦理考虑，在女性中进行结论性研究是困难的。我们开发了一种更年期的猴子模型，它绕过了这些限制，并使我们能够研究灵长类动物大脑中卵巢激素作用的潜在机制。我们正在进行一项纵向研究，以评估手术绝经（卵巢切除术）和随后的激素替代治疗对老年雌性恒河猴记忆力和注意力的影响。这项研究正在验证卵巢切除术会损害认知功能，而激素治疗会恢复或改善认知功能的假设。行为研究与脑结构的非侵入性磁共振成像测量平行进行，以确定总脑体积或特定皮质区域的体积是否因衰老和卵巢激素的退出和替代而改变，以及脑结构参数是否与认知能力相关。这些研究提供了卵巢激素对老年女性大脑功能影响的对照测试，以及有关潜在大脑机制的证据。他们将直接关系到困难和有争议的问题卵巢激素替代更年期妇女。

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.