The presentation and medical course of PCOS in adolescents across the United States

1多囊卵巢综合征(PCOS)是女性最常见的内分泌疾病之一，表现为 2青春期无排卵和高雄激素血症。除了生殖异常，多囊卵巢综合征还 3经常与肥胖和代谢并发症有关，包括糖尿病、非酒精性脂肪肝 4疾病、阻塞性睡眠呼吸暂停、高血压、高脂血症。此外，患有多囊卵巢综合征的女性 5有精神健康障碍和明显的皮肤病表现。多囊卵巢综合征是一种慢性疾病 6异质性家族性疾病，因此诊断时的症状、体征和合并症各不相同。尽管 7与多囊卵巢综合征相关的高患病率和严重并发症，广泛有效的治疗选择是 缺少8个。未寻求怀孕的妇女治疗多囊卵巢综合征的推荐疗法包括雌激素 9含有避孕药(EC)、改变生活方式和二甲双胍。最近，有人呼吁采取更多措施 10种个体化和个性化的治疗方法，但推荐其中一种的生物学基础很少 11次治疗胜过另一次治疗。此外，尽管这些治疗方案已有40多年的历史，但对 12它们对患有多囊卵巢综合征的青少年的疗效仅限于小规模研究。此外，由于青春期特有的激素 13个变化中，青少年的胰岛素敏感性低于成年人。事实上，一些研究已经确立了 14患有糖尿病或肥胖症的青少年对二甲双胍的反应比成年人更少。因此，来自药物试验的数据 15名成年妇女不能适用于患有多囊卵巢综合征的青年。 16美国目前还没有机制来询问早期的自然历史和对 在患有多囊卵巢综合征的不同青年人群中使用17种现有药物。vbl.使用 18个机构的研究发现，没有肥胖的女孩的生殖异常更严重，而且代谢异常 19肥胖症的并存在女孩中更为常见。此外，我们和其他人发现多囊卵巢综合征 20陈述，特别是与合并症有关的陈述，可能反映了根本的种族和族裔差异。这个 21该项目的总体目标是描述目前的生殖和代谢表型、自然病史、 22和对患有多囊卵巢综合征的地理、族裔和种族多样化的青年进行大样本的治疗反应。我们 23假设多囊卵巢综合征在青春期的表现会因家族史、肥胖、种族和民族而异 24个状态，诊断时的独特因素可用于识别对EC、二甲双胍或 25种生活方式疗法。Sa1)描述青年多囊卵巢综合征诊断时的表现和合并症 26在美国SA2)确定对常见药物(生活方式、EC、二甲双胍)的反应。这 27个队列代表了患有多囊卵巢综合征的非常多样化的青年人群，该数据库是第一个针对青年的此类数据库 多囊卵巢综合征28例。这项工作将建立早期表型如何影响更个性化的方法 29.初步治疗。这些努力是开发数据信息个性化治疗的关键第一步 30计划改善患有多囊卵巢综合征的女孩的长期健康。 汇集了来自6个国家的回顾数据 W

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 individualized approaches toward 29 initial therapy. These efforts are a critical first step towards developing data-informed personalized treatment 30 plans to improve the long-term health of girls with PCOS. pooled retrospective data from 6 w