Postmenopausal Monkey Resource

描述(由申请人提供)：妇女健康倡议试验(WHI)单独使用结合马类雌激素(Premarin)或与甲孕酮(Prempro)联合使用，已将更年期妇女的健康问题变成了雷区。由于乳腺癌发病率增加，联合激素组过早终止。与安慰剂相比，两组患者患动脉粥样硬化、中风和认知能力下降的风险都有所增加。虽然WHI试验揭示了绝经后女性服用Prempro的风险，但它在该领域引起了相当大的争议，因为它被解释为绝经后激素替代的起诉书，而事实上，它并没有研究激素替代，这需要使用天然激素、雌二醇(E)和孕酮。天然激素的作用与倍美力或倍美力的作用有很大不同。此外，WHI在绝经后十年或更长时间注射合成激素，这引发了激素治疗是否存在最佳时间框架的问题。已经有了后续研究，这些研究使用了自然激素，并表明确实需要在围绝经期给药，但终点仅限于一个或两个系统。我们假设，在卵巢切除/子宫切除(OVX)后立即开始雌激素(E)替代将是有益的，但延迟治疗对研究中的许多系统没有好处，甚至是不利的。我们建议建立一个绝经后猕猴资源，用西式饮食和安慰剂、立即-E或延迟-E替代治疗老年OVX恒河猴。我们将获得对社会行为、活动、温度、认知功能、大脑结构、免疫功能、脂肪积累、葡萄糖代谢和骨密度的纵向评估。我们将获得冠状动脉、乳房组织、脂肪胰岛素敏感性的尸检评估，并确定多个神经系统的细胞和分子功能。 公共卫生相关性(由申请者提供)：该资源将成为中年晚期妇女完全子宫切除术后的杰出典范，在很大程度上模仿更年期。更年期卵巢类固醇激素的丢失会影响女性的许多生理系统，但激素治疗的配方和时机存在争议。我们的项目将向所有人提供有关雌激素治疗最佳和安全使用的关键信息。

DESCRIPTION (provided by applicant): The Women's Health Initiative trial (WHI), which employed conjugated equine estrogens alone (Premarin) or in conjunction with MPA (Prempro) has turned women's health at menopause into a minefield. The combined hormone arm was ended prematurely due to increased incidence of breast cancer. Increased risk of artherosclerosis, stroke and cognitive decline was also present in both arms relative to placebo. While the WHI trial revealed the risks associated with Prempro in post-menopausal women, it generated considerable controversy in the field because it was interpreted as an indictment of post-menopausal hormone replacement, when in fact, it did not study hormone replacement, which would have required use of the natural hormones, estradiol (E) and progesterone. The actions of the natural hormones are significantly different from those of Premarin or Prempro. In addition, WHI administered the synthetic hormones a decade or more after menopause, raising the question of whether there is an optimal time frame for hormone therapy. There have been follow up studies, which have used natural hormones and shown that indeed, they need to be administered at perimenopause, but the endpoints were limited to one or two systems. We hypothesize that estrogen (E) replacement will be beneficial when started immediately after ovariectomy/hysterectomy (Ovx), but delayed treatment will have no beneficial, or even adverse, effects on many of the systems under study. We propose to establish a postmenopausal monkey resource with aged Ovx rhesus monkeys on a Western diet and treated with placebo, immediate-E or delayed-E replacement. We will obtain longitudinal assessments of social behavior, activity, temperature, cognitive function, brain structure, immune function, fat accumulation, glucose metabolism and bone density. We will obtain postmortem assessments of coronary arteries, breast tissue, fat insulin sensitivity, and determine the cellular and molecular function of multiple neural systems. PUBLIC HEALTH RELEVANCE (provided by applicant): This resource will be an outstanding model of late middle aged women after complete hysterectomy, which mimics menopause in significant ways. The loss of ovarian steroids at menopause impacts many physiological systems in women, but the formulation and timing of hormone therapy is controversial. Our project will provide critical information to all on the optimal and safe use of estrogen therapy.