1 Polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in women, presents with 2 anovulation and hyperandrogenism in adolescence. In addition to reproductive abnormalities, PCOS is 3 frequently associated with obesity and metabolic complications including diabetes, non-alcoholic fatty liver 4 disease, obstructive sleep apnea, hypertension and hyperlipidemia. Additionally, women with PCOS are more 5 likely to suffer from mental health disorders and significant dermatologic manifestations. PCOS is a chronic 6 heterogeneous familial disorder and thus symptoms, signs and co-morbidities at time of diagnosis vary. Despite 7 the high prevalence and gravity of comorbidities associated with PCOS, widely effective therapeutic options are 8 lacking. Recommended therapies for PCOS treatment in women not seeking pregnancy include estrogen 9 containing contraceptives (EC), lifestyle modification, and metformin. Recently there has been a call for more 10 individualized and personalized therapeutic approaches, however there is little biologic basis to recommend one 11 therapy over another. Further, despite the availability of these treatment options for over 40 years, research on 12 their efficacy in youth with PCOS is limited to small studies. Additionally, due to puberty specific hormone 13 changes, adolescents have lower insulin sensitivity than adults. Indeed, a number of studies have established 14 that youth with diabetes or obesity respond less to metformin than adults. Thus, data from medication trials in 15 adult women cannot be applied in youth with PCOS. 16 No mechanism is currently available in the United States to query the early natural history and response to 17 existing medications in a diverse population of youth with PCOS. Using 18 institutions, e found that reproductive abnormalities are more severe in girls without obesity, and metabolic 19 co-morbidities are more common in girls with obesity. Additionally, we and others have found that PCOS 20 presentation, especially as relates to comorbidities, may reflect underling racial and ethnic differences. The 21 overall goal of the project is to describe the presenting reproductive and metabolic phenotypes, natural history, 22 and response to therapy in a large sample of geographically, ethnically and racially diverse youth with PCOS. We 23 hypothesize that presentations of PCOS in adolescence will vary by family history, obesity, and race and ethnicity 24 status, and that unique factors at diagnosis can be used to identify those that respond to EC, metformin or 25 lifestyle therapies. SA1) Describe the presentation and co-morbidities at the time of diagnosis of PCOS in youth 26 in the United States SA2) Determine the response to common medications (lifestyle, EC, metformin). This 27 cohort represents a very diverse population of youth with PCOS, and the database is the first of its kind for youth 28 with PCOS. This work will establish how early phenotypes can inform more...