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

基本信息

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
项目类别：
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

项目摘要

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.

性腺衰老在介导衰老引起的一些生物学变化中发挥着独特的作用过程。一个例子是更年期时由于卵巢功能衰竭而加速骨质流失，通过恢复雌激素可以有效缓解，直到其他非性腺衰老因素触发下降。由于很难将性腺衰老的后果与时间性衰老区分开来，因此不能明确性腺功能丧失在多大程度上会增加除年龄相关疾病之外的其他疾病的风险骨质疏松症。对雌性和雄性动物的研究有令人信服的证据表明，性腺的丧失功能下降导致自发体力活动急剧下降 30% 至 80%。在女性中，但不是对于男性来说，这会导致体重加速增加、腹部脂肪显着增加和代谢功能障碍。一项针对更年期过渡期女性的前瞻性研究表明，体力活动能量平衡的维持也受到人类性腺功能的调节。在此背景下， UCAMC SCOR 临床项目的主要目标是使用受控干预方法确定接近更年期的女性卵巢功能受到抑制是否会导致体力活动明显下降。其他目标是评估能源其他组成部分的变化支出，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，并确定计划锻炼是否可以预防这些变化。为了实现这些目标是，66 名 45 至 50 岁、月经周期功能正常的女性将被随机分配接受 6 数月的安慰剂、促性腺激素释放激素激动剂 (GnRHAc) 或 GnRHAG+运动干预。主要结果是身体活动能量消耗 (PAEE)，根据每日总能量计算远期（TEE；双标记水），调整食物和静息 EE 的热效应（REE；通过间接量热法）。普遍的假设是 GnRHAG 抑制卵巢功能女性会因 PAEE 下降而导致 TEE 下降，并且可能还会导致 REE 下降。相关性（参见说明）：性腺功能丧失继发的 PAEE 下降可能对健康产生多种不利影响因为体力活动不足与全因死亡率、冠心病、中风、2 型糖尿病相关糖尿病、某些癌症、抑郁症等。此外，预计这会产生更大的不利影响对女性的影响大于对男性的影响，因为女性性腺功能丧失的年龄较早。