Postmenopausal Monkey Resource

绝经后猴子资源

• 批准号: 8337472
• 负责人: CYNTHIA Louise BETHEA
• 金额: $ 84.76万
• 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/8337472
• 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. 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.

描述（由申请人提供）：妇女健康倡议试验（WHI），其中采用共轭马雌激素单独（倍美力）或与MPA（Prempro）结合已成为妇女的健康在更年期雷区。由于乳腺癌的发病率增加，联合激素组提前结束。与安慰剂组相比，两组患者的关节炎、中风和认知能力下降的风险均增加。虽然WHI试验揭示了绝经后妇女与Prempro相关的风险，但它在该领域产生了相当大的争议，因为它被解释为对绝经后激素替代的起诉，而事实上，它没有研究激素替代，这需要使用天然激素，雌二醇（E）和孕酮。天然激素的作用与Premarin或Prempro的作用有显着不同。此外，WHI在绝经十年或更长时间后给予合成激素，这提出了激素治疗是否有最佳时间框架的问题。已经有后续研究，使用天然激素，并表明确实需要在围绝经期使用，但终点仅限于一个或两个系统。我们假设，雌激素（E）替代治疗在卵巢切除术/子宫切除术（Ovx）后立即开始是有益的，但延迟治疗对许多正在研究的系统没有益处，甚至有不良影响。我们建议建立一个绝经后的猴资源与老年Ovx恒河猴西方饮食和治疗安慰剂，立即E或延迟E替代。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。我们将对冠状动脉、乳腺组织、脂肪胰岛素敏感性进行尸检评估，并确定多个神经系统的细胞和分子功能。 公共卫生相关性（由申请人提供）：此资源将是完全子宫切除术后的中年妇女的杰出模型，这在很大程度上模拟了更年期。绝经期卵巢类固醇的损失会影响女性的许多生理系统，但激素治疗的制定和时机是有争议的。我们的项目将为所有人提供关于最佳和安全使用雌激素治疗的关键信息。