The fetal and early childhood origins of PCOS: A prospective cohort study

多囊卵巢综合征(PCOS)影响高达10%的育龄妇女，相当于澳大利亚约35万名妇女。这是女性最常见的荷尔蒙紊乱。这种综合征对全身和生殖健康具有深远的不利影响，包括月经失调、肥胖、不孕、流产、妊娠并发症、糖尿病风险增加，可能还有心脏病。多囊卵巢综合征还通常会导致美容问题，如体毛过多和粉刺。多囊卵巢综合征的根本原因尚不清楚，但被认为出现在宫内(胎儿)生活中，并受到儿童健康方面的影响，特别是超重和肥胖。利用从胎儿期到整个儿童期、目前年龄在13-15岁之间的一大批成熟的青少年队列(Raine队列)，我们将首次确定多囊卵巢综合征的宫内和儿童早期相关因素。多囊卵巢综合征将由一名妇科专家使用当前的国际标准进行诊断。然后，我们将利用这一队列中广泛的现有数据，结合对现有样本的新测量，确定关键因素对多囊卵巢综合征的影响，这些因素包括胎儿生长受限、低出生体重、胎儿雄激素暴露、出生后快速发育、儿童肥胖、空腹血糖和胰岛素升高以及月经初潮年龄。通过这种方式，我们将首次提出多囊卵巢综合征是胎儿时期事件的结果，并受到童年时期因素的影响的假说。这些研究的结果将增进我们对多囊卵巢综合征的了解，并最终改善国际上相当一部分妇女的生殖和代谢健康。必须尽快进行这些研究，否则就会错失良机。持续月经不规律的女孩很可能会开始接受激素治疗，这将使多囊卵巢综合征的诊断变得不可能。

The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and acne. The underlying causes of PCOS are not known but are thought to arise during intrauterine (fetal) life and to be modified by aspects of childhood health, particularly overweight and obesity. Using a large and well established cohort of adolescents followed up since fetal life and throughout childhood and currently aged 13-15 years old (the Raine cohort), we will define for the first time the intrauterine and early childhood correlates of PCOS. PCOS will be diagnosed by a specialist gynacologist using current international criteria. We will then utilise extensive existing data from this cohort combined with new measurements on existing samples to determine the contribution of key factors including fetal growth restriction, low birth weight, fetal androgen exposure, rapid postnatal growth, childhood adiposity, elevated fasting glucose and insulin and age at menarche to PCOS. In this way, we will address for the first time the hypothesis that PCOS arises as a result of events during fetal life and is affected by factors during childhood. The results from these studies will improve our understanding of PCOS and eventually improve reproductive and metabolic health for a substantial population of women internationally. It is essential that these studies are conducted as soon as possible or the opportunity will be missed. Girls with persistent menstrual irregularity are likely to be commenced on hormonal treatments which will make the diagnosis of PCOS impossible.