Postmenopausal Monkey Resource

描述（由申请人提供）：妇女健康倡议试验 (WHI) 单独使用结合马雌激素 (Premarin) 或与 MPA (Prempro) 结合使用，使更年期妇女的健康变成了一个雷区。由于乳腺癌发病率增加，联合激素组提前结束。与安慰剂相比，双臂的动脉粥样硬化、中风和认知能力下降的风险也增加。虽然 WHI 试验揭示了与 Prempro 对绝经后妇女相关的风险，但它在该领域引起了相当大的争议，因为它被解释为对绝经后激素替代的控诉，而事实上，它没有研究激素替代，而激素替代需要使用天然激素、雌二醇 (E) 和黄体酮。天然激素的作用与 Premarin 或 Prempro 的作用显着不同。此外，WHI 在绝经后十年或更长时间使用合成激素，引发了激素治疗是否存在最佳时间范围的问题。后续研究使用了天然激素，并表明确实需要在围绝经期施用，但终点仅限于一两个系统。我们假设在卵巢切除术/子宫切除术 (Ovx) 后立即开始补充雌激素 (E) 将是有益的，但延迟治疗不会对许多正在研究的系统产生有益甚至不利的影响。我们建议建立一个绝经后猴子资源，其中包括采用西方饮食并接受安慰剂、立即 E 或延迟 E 替代疗法的老年 Ovx 恒河猴。我们将获得社会行为、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、乳腺组织、脂肪胰岛素敏感性的死后评估，并确定多个神经系统的细胞和分子功能。 公共健康相关性（由申请人提供）：该资源将成为中年晚期女性完全子宫切除术后的杰出模型，在很大程度上模仿了更年期。更年期卵巢类固醇的丧失会影响女性的许多生理系统，但激素治疗的配方和时机仍存在争议。我们的项目将为所有人提供有关最佳和安全使用雌激素疗法的重要信息。

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.