Postmenopausal Monkey Resource

绝经后猴子资源

• 批准号: 8705065
• 负责人: CYNTHIA Louise BETHEA
• 金额: $ 53.46万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-18 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705065
• 关键词: Adverse effects; Amygdaloid structure; Animals; Autopsy; Bone Density; Brain; Conjugated Equine Estrogens; Conjugated Estrogens; Coronary artery; Diet; Dopamine; Drug Formulations; Equus caballus; Estradiol; Estrogen Therapy; Estrogens; Fatty acid glycerol esters; Follow-Up Studies; Hippocampus (Brain); Hormones; Hypothalamic structure; Hysterectomy; Impaired cognition; In Situ Hybridization; Incidence; Macaca; Macaca mulatta; Mammary Gland Parenchyma; Menopause; Modeling; Molecular; Monkeys; Ovarian; Ovariectomy; Perimenopause; Physiological; Placebos; Postmenopause; Prefrontal Cortex; Prempro; Progesterone; Relative (related person); Resources; Risk; Serotonin; Sleep Wake Cycle; Social Behavior; Steroids; Stroke; Structure; Surgical Models; System; Temperature; Time; Total Hysterectomy; Woman; Women' s Health; aged; animal resource; arm; cognitive function; follow-up; glucose metabolism; hormone therapy; immune function; immunocytochemistry; insulin sensitivity; malignant breast neoplasm; middle age; mortality; norepinephrine system; relating to nervous system

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.

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) 联合使用，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 试验揭示了绝经后妇女与 Prempro 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，它并没有研究激素替代，这会导致需要使用天然激素、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。