Cognition and Estrogen in Middle-Aged Female Monkeys

描述（由申请人提供）：本申请是作为授予RO1AG19100的补充提交的，标题为“中年雌性猴子的认知和雌激素”。 更年期的卵巢激素缺乏症会带来变化，可能对女性未来的健康和福祉产生深远的影响。除了与绝经相关的身体症状外，绝经后妇女还经历认知功能的改变，特别是记忆力和注意力。然而，由于各种混杂因素，在女性中确定卵巢激素和更年期认知功能之间的关系可能很难研究。我们已经开发了一个更年期的猴子模型，使我们能够更严格地控制这些因素中的许多因素，此外，这将使我们能够确定灵长类动物大脑中卵巢激素作用的潜在机制。母项目研究的重点是确定卵巢切除术和无对抗性连续雌激素替代疗法（ERT）对俄勒冈州地区灵长类动物研究中心（ORPRC）一个独特的中年雌性恒河猴群体认知能力的影响。本补充申请的目的是通过增加另一组将接受持续雌激素和孕激素（HRT）联合治疗的卵巢切除猴，并通过在所有猴（补充组和原始组）中进行MRI研究，扩大可从母项目中获得的有价值信息的范围。 增加新的猴组将允许直接比较ERT和HRT治疗对认知功能的影响。联合HRT不仅是绝经后妇女最常用的卵巢激素替代疗法，它也代表了一种激素替代疗法，比连续无对抗性ERT更接近绝经前妇女雌激素和孕激素的自然生理暴露。MRI研究将确定卵巢切除术或卵巢激素治疗对随年龄下降的脑体积测量的影响程度，以及这些体积变化与认知功能之间是否存在相关性。本补充申请中的试验将利用已经得到母公司赠款支助的治疗组和对照组的存在，解决妇女健康的关键问题。在中年猴子中进行的这些新实验的结果将大大促进我们对不同卵巢激素疗法对灵长类动物认知和神经生物学特征影响的理解。

DESCRIPTION (provided by applicant): This application is being submitted as a supplement to grant RO1AG19100 entitled "Cognition and Estrogen in Middle-Aged Female Monkeys". Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. In addition to the physical symptoms associated with menopause, postmenopausal women experience alterations in cognitive function, particularly memory and attention. However, determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and, additionally, that will permit us to identify the potential mechanisms of ovarian hormone action in the primate brain. The focus of the studies in the parent project is to determine the effects of ovariectomy and unopposed continuous estrogen replacement therapy (ERT) on cognitive abilities in a unique colony of middle-aged female rhesus monkeys at the Oregon Regional Primate Research Center (ORPRC). The purpose of this supplemental application is to expand the breadth of valuable information that could be obtained from the parent project by adding another group of ovariectomized monkeys that will be treated with a combined therapy of continuous estrogen and progesterone (HRT) and by performing MRI studies in all monkeys (supplemental and original groups). The addition of the new group of monkeys will permit the direct comparison between ERT and HRT treatments on cognitive function. Combined HRT is not only the most commonly prescribed ovarian hormone replacement therapy of postmenopausal women; it also represents a hormone replacement therapy that more closely mimics the natural physiological exposure to estrogen and progesterone in premenopausal women than continuous unopposed ERT alone. The MRI studies will determine the extent to which ovariectomy or ovarian hormone therapy influence measures of brain volume that decline with age, and whether there is a correlation between these volumetric changes and cognitive function. The experiments in this supplemental application will address key issues of women's health by taking advantage of the existence of the treatment and control groups already supported by the parent grant. The findings from these novel experiments in middle-aged monkeys will significantly advance our understanding of the effects of different ovarian hormone therapies on cognitive and neurobiological profiles of primates.