Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women

女性卵巢功能丧失的生物能和代谢后果

• 批准号: 8367337
• 负责人: Wendy M Kohrt
• 金额: $ 50.2万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367337
• 关键词: Adverse effects; Age; Age Factors; Aging; Aging-Related Process; Agonist; American; Animals; Attenuated; Bioenergetics; Biological; Biological Markers; Bone Density; Chronic Disease; Clinical; Colon Carcinoma; Coronary heart disease; Disease; Energy Metabolism; Estrogens; Exercise; Failure; Fasting; Fatty acid glycerol esters; Female; Figs - dietary; Food; Functional disorder; Goals; Gonadotropin Hormone Releasing Hormone; Guidelines; Health; Human; Hypertension; Indirect Calorimetry; Inflammation; Inflammatory; Instruction; Insulin Resistance; Intervention; Label; Life; Maintenance; Malignant Neoplasms; Measures; Mediating; Menopause; Menstrual cycle; Mental Depression; Metabolic; Metabolic Control; Metabolic syndrome; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Observational Study; Orchiectomy; Osteoporosis; Ovarian; Ovarian Ablation; Ovariectomy; Physical activity; Placebos; Play; Principal Investigator; Prospective Studies; Randomized; Relative (related person); Reporting; Research; Rest; Risk; Role; Secondary to; Serum; Sleep; Stroke; Techniques; Testosterone; Time; Water; Weight Gain; Woman; abdominal fat; age related; aged; base; bone loss; cytokine; disorder risk; energy balance; feeding; fitness; gonad function; male; malignant breast neoplasm; men; mortality; prevent; primary outcome; programs; response; restoration; secondary outcome; skeletal

Gonadal aging plays a distinct role in mediating some of the biological changes ascribed to the aging process. An example of this is the accelerated bone loss due to ovarian failure at the time of the menopause, which can be effectively mitigated with restoration of estrogens until other non-gonadal aging factors trigger a decline. Because it is difficult to isolate the consequences of gonadal aging from chronologic aging, it is not clear to what extent the loss of gonadal function increases risk for age-related diseases other than osteoporosis. There is compelling evidence from studies of female and male animals that the loss of gonadal function causes a dramatic decline of 30% to 80% in spontaneous physical activity. In females, but not males, this leads to accelerated weight gain, a marked increase in abdominal fat, and metabolic dysfunction. One prospective study of women followed through the menopausal transition suggests that physical activity and the maintenance of energy balance are also regulated by gonadal function in humans. In this context, the primary goal of the UCAMC SCOR clinical project is to use a controlled intervention approach to determine whether the suppression of ovarian function in women approaching the menopause causes a marked decline in physical activity. Additional goals are to assess changes in other components of energy expenditure, determine whether the disruption of energy balance is associated with changes in biomarkers of disease risk, and determine whether programmed exercise can prevent these changes. To achieve these aims, 66 women aged 45 to 50 years with normal menstrual cycle function will be randomized to receive 6 months of placebo, gonadotropin releasing hormone agonist (GnRHAc), or GnRHAG+exercise intervention. The primary outcome will be physical activity energy expenditure (PAEE), calculated from total daily energy expediture (TEE; by doubly-labeled water) with adjustment for the thermic effect of food and resting EE (REE; by indirect calorimetry). The global hypothesis is that the suppression of ovarian function with GnRHAG in women will cause a decrease in TEE due to decreased PAEE and, possibly, a decrease in REE. RELEVANCE (See instructions): A decline in PAEE secondary to the loss of gonadal function could have diverse adverse effects on health because low physical activity is associated with all-cause mortality, coronary heart disease, stroke, type 2 diabetes, certain cancers, depression, etc. Moreover, this would be expected to have a greater adverse effect in women than in men, because the loss of gonadal function occurs at an earlier age in women.

性腺衰老在介导某些归因于衰老的生物学变化中起着独特的作用 过程这方面的一个例子是在绝经期由于卵巢衰竭而加速的骨质流失， 这可以通过恢复雌激素来有效缓解，直到其他非性腺老化因素触发 下降因为很难将性腺老化的后果与时间老化分开， 清楚性腺功能丧失在多大程度上增加了除以下疾病外的与年龄有关的疾病的风险 骨质疏松对雌性和雄性动物的研究有令人信服的证据表明， 功能的丧失导致自发性体力活动急剧下降30%至80%。在女性中， 对于男性，这会导致体重加速增加，腹部脂肪显著增加，以及代谢功能障碍。 一项对绝经过渡期妇女的前瞻性研究表明， 以及维持能量平衡也受人类性腺功能的调节。在这一背景下， UCAMC SCOR临床项目的主要目标是使用受控干预方法， 确定接近绝经期的女性卵巢功能抑制是否会导致 体力活动明显减少。其他目标是评估能源其他组成部分的变化 消耗，确定能量平衡的破坏是否与生物标志物的变化有关。 疾病风险，并确定是否有计划的锻炼可以防止这些变化。实现这些 66名年龄45 - 50岁月经周期功能正常的妇女将随机接受6种 安慰剂、促性腺激素释放激素激动剂（GnRHAC）或GnRHAG+运动干预治疗3个月。 主要结果将是体力活动能量消耗（PAEE），根据每日总能量计算 快速（TEE;通过双标记水），调整食物和静息EE的热效应 (REE通过间接量热法）。总体假设是GnRHAG抑制卵巢功能 在女性中，由于PAEE降低，TEE也可能降低REE。 相关性（参见说明）： 继发于性腺功能丧失的PAEE下降可能对健康产生各种不良影响 由于低体力活动与全因死亡率、冠心病、中风、2型相关 糖尿病，某些癌症，抑郁症等。此外，这将是预期有更大的不利 女性的效果比男性好，因为女性性腺功能的丧失发生在更早的年龄。