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

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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.