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.

性腺衰老在介导归因于衰老的某些生物学变化中起着独特的作用过程。一个例子是由于绝经时卵巢衰竭而导致的加速骨质流失，可以通过恢复雌激素的恢复有效地缓解这种方法，直到其他非助剂衰老因素触发下降。因为很难将性腺衰老的后果与年代衰老隔离开来，所以不是明确在多大程度上损失性腺功能会增加与年龄相关疾病以外的其他疾病的风险骨质疏松症。从研究女性和男性动物的研究中有令人信服的证据表明性腺丧失功能会导致自发的体育活动显着下降30％至80％。在女性中，但不是雄性，这导致体重增加，腹部脂肪显着增加和代谢功能障碍。对妇女进行的一项前瞻性研究，然后通过更年期过渡表明体育锻炼能量平衡的维持也受到人类性腺功能的调节。在这种情况下， UCAMC SCOR临床项目的主要目标是使用受控干预方法确定在更年期接近女性卵巢功能的抑制是否会导致体育锻炼明显下降。其他目标是评估其他能源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的风险，并确定编程运动是否可以防止这些变化。实现这些目的，66名45至50岁的女性具有正常的月经周期功能，将随机分配6 安慰剂月份，促性腺激素释放激素激动剂（GNRHAC）或GNRHAG+运动干预。主要结果将是体育锻炼能量消耗（PAEE），根据每日总能量计算加速（TEE；通过双标记的水）调整食物和静止EE的热效应（REE；通过间接量热法）。全球假设是用Gnrhag抑制卵巢功能在女性中，由于PAEE的减少，可能会导致TEE减少，并且可能会减少REE。相关性（请参阅说明）：继发性腺功能丧失之后的PAEE下降可能会对健康产生不同的不利影响因为身体活动较低与全因死亡率，冠心病，中风，2型有关此外，糖尿病，某些癌症，抑郁症等。此外，预计这会有更大的不利女性的影响比男性的影响，因为性腺功能的丧失发生在女性的早期。