Investigating the impact of physical activity in modulating PCOS risk among peripubertal females

项目摘要 多囊卵巢综合征(PCOS)在全球每10名女性中就有1名患病。而PCOS是 它的主要特征是月经不规律和高雄激素血症，也与 患有多种合并症--包括糖尿病、心血管疾病、抑郁症和 不孕不育--这会导致相当大的发病率和医疗费用。复杂的互动 肥胖、胰岛素敏感性降低和雄激素浓度升高之间的关系 是多囊卵巢综合征的病理生理学基础。这些迹象通常最早出现在青春期早期， 这是预防性干预的关键机会。虽然体力活动是一种有希望的 针对多囊卵巢综合征发展的潜在因素的策略，有重要的文献 在预防多囊卵巢综合征的有效战略方面存在差距。这项提议的目标是 确定女性胰岛素动态和雄激素浓度变化的时间进程 从儿童期中期到青春期和早期体力活动的影响 这些终点上的青春期(目标1)，并使用实施科学方法加以改进 (目标2)并试点在青春期周围进行有针对性的循证体力活动干预 8-10岁的女孩有多囊卵巢综合征的风险，同时评估干预的可行性、可接受性和 初步疗效与体力活动水平、胰岛素敏感性和雄激素的关系 浓度(目标3)。这项研究的发现将为发展、传播、 和实施有效和可扩展的预防干预措施，这是 NIDDK。此外，通过专门针对有可能患上后来的代谢性疾病的年轻女性， 这项建议采取了一种终生方法来预防慢性病。私家侦探，胡腾博士， 是一名早期职业的临床医生研究员和儿科内分泌学家，以及健康服务 研究员。她将利用这个职业发展奖来培养她在(1)纵向的技能 流行病学队列分析，(2)行为干预措施的设计和实施 由实施科学方法提供信息，以及(3)收集和衡量 客观的行为和生理结果，这将是评估干预的关键 功效。胡腾博士将与一个多学科的指导和咨询团队密切合作 具有流行病学专业知识，对健康行为的客观衡量，对 实施HER的内分泌生理结果、实施科学和生物统计学 明确的职业目标和具体目标。

PROJECT ABSTRACT Polycystic Ovary Syndrome (PCOS) affects 1 out of 10 women worldwide. While PCOS is primarily characterized by menstrual irregularity and hyperandrogenemia, it is also associated with multiple comorbidities – including diabetes, cardiovascular disease, depression, and infertility – that lead to substantial morbidity and health care costs. A complex interaction between adiposity, decreased insulin sensitivity, and increased androgen concentrations underlies the pathophysiology of PCOS. These signs often first appear in early adolescence, representing a key opportunity for preventive interventions. While physical activity is a promising strategy for targeting the factors underlying PCOS development, there is a significant literature gap regarding effective strategies for use in PCOS prevention. The goal of this proposal is to identify the time course of changes in insulin dynamics and androgen concentrations in females from mid-childhood through adolescence and the impact of physical activity during early adolescence on these endpoints (Aim 1) and use implementation science methods to refine (Aim 2) and pilot a targeted and evidence-based physical activity intervention in peripubertal girls ages 8-10 at risk for PCOS while assessing the interventions’ feasibility, acceptability, and preliminary efficacy in relation to physical activity levels, insulin sensitivity, and androgen concentrations (Aim 3). The findings from this study will inform the development, dissemination, and implementation of effective and scalable preventive interventions, a high priority area for the NIDDK. Additionally, by specifically targeting young females at risk for later metabolic disease, this proposal takes a life-course approach to chronic disease prevention. The PI, Dr. Whooten, is an early career clinician investigator and pediatric endocrinologist, as well as health services researcher. She will use this career development award to build her skills in (1) the longitudinal analysis of epidemiological cohorts, (2) design and implementation of behavioral interventions informed by an implementation science approach, and (3) collection and measurement of objective behavioral and physiologic outcomes which will be essential for evaluating intervention efficacy. Dr. Whooten will work closely with a multidisciplinary mentorship and advisory team with expertise in epidemiology, objective measurement of health behaviors, measurement of endocrine physiologic outcomes, implementation science, and biostatistics to carry out her stated career objectives and specific aims.