Longitudinal study of endocrine disrupting chemical exposure and the early hormonal milieu of girls around the time of thelarche

项目总结： 女孩内分泌干扰物暴露与早期激素环境的纵向研究 大约在泰勒契时代 内分泌干扰物(EDCs)是一种外源性物质，在体内表现出激素活性 内分泌系统，扰乱内源性激素的生理功能。青春期周围时期 代表了易受环境暴露的发展窗口，在这一窗口中，EDC可以充当 内源性激素的激动剂或拮抗剂。将内分泌细胞与青春期改变直接联系起来的证据 人类群体的发展远远不是决定性的。直接与暴露于EDCs和 女孩在乳房发育期间的血清类固醇激素水平几乎不存在变化。 以前对青春期女孩的研究(包括我们这群人和其他人)都报告说，接触某些 EDC与较晚或较早的初潮和月经初潮有关，这表明EDC可能有一个 青春期女孩荷尔蒙环境的影响。这些研究中没有一项检查过一种混合的 环境暴露与青春期活动的年龄有关。关于结构关系的知识 关于EDCs对女孩激素水平的直接影响，然后是青春期后期的时间和强度 事件，如初潮年龄、月经初潮年龄、青春期节奏、高峰速度和高峰年龄 身高，是不够的。通过在我们的女孩队列中测量多种环境生物标记物，我们可以 制定混合环境暴露的指标，并在我们的分析中使用这些指标。带着我们的 前瞻性研究设计包括对青春期成熟事件的直接观察和对 在月经初潮前后血清中的类固醇激素，我们可以检测暴露于内皮细胞对 这些事件使用结构方程模型。我们的研究建议填补关于以下方面的知识空白 暴露于EDCs是否对青春期女孩的荷尔蒙环境有直接影响，以及这些变化是如何发生的 In与青春期里程碑的年龄有关。 这个应用程序具有很高的创新性，因为它的独特设计：女孩已经被评估 纵向从6-7岁开始，在乳突周围的时间点进行血清激素测量， 以及青春期前环境生物标记物的测量。我们的假设是新颖的。使用现有的 前瞻性地收集青春期成熟和环境生物标记物数据，最近获得 一组女孩成熟期血清样本中血清激素的测定 从6岁和7岁开始，我们将直接解决2013年IBCERCC报告中指出的差距 癌症与环境：优先预防“。这项提案的影响是提供以下信息 将导致确定内分泌细胞的机制和有针对性的途径，从而制定战略 最大限度地减少女孩青春期事件的时间中断和成人未来不良健康后果的风险 女人。

PROJECT SUMMARY: Longitudinal Study of Endocrine-Disrupting Chemical Exposure and the Early Hormonal Milieu of Girls Around the Time of Thelarche Endocrine disrupting chemicals (EDCs) are exogenous substances which exhibit hormonal activity in the endocrine system, disrupting the physiologic function of endogenous hormones. The peri-pubertal period represents a developmental window of vulnerability to environmental exposures in which EDCs may act as agonists or antagonists to endogenous hormones. Evidence directly linking EDCs and alterations in pubertal development in human populations is far from conclusive. Evidence directly linking exposure to EDCs and changes in serum steroid hormone levels in girls around the time of breast development is almost non-existent. Previous studies of pubertal girls (both in our cohort and others) have reported that exposure to certain EDCs is associated with either later or earlier thelarche and menarche suggesting that EDCs may have an effect on the hormonal milieu in pubertal girls. None of these studies has examined whether a mixture of environmental exposures is related to age at pubertal events. Knowledge about the structural relationship regarding the direct effect of EDCs on hormone levels in girls and then the timing and intensity of later pubertal events, such as age at thelarche, age at menarche, pubertal tempo, peak height velocity, and age at peak height, is lacking. With the measurement of multiple environmental biomarkers in our cohort of girls, we can develop metrics for mixtures of environmental exposures and use these metrics in our analyses. With our prospective study design including direct observation of pubertal maturation events and measurements of steroid hormones in serum around the time of thelarche, we can examine the effect of exposure to EDCs on these events using structural equation models. Our study proposes to fill the gap in knowledge regarding whether exposure to EDCs has a direct effect on the hormonal milieu in pubertal girls, and how these changes in are related to age at pubertal milestones. This application is highly innovative because of its unique design: girls have been evaluated longitudinally from ages 6-7 years, with serum hormone measurements during time points around thelarche, and measurements of environmental biomarkers prior to puberty. Our hypotheses are novel. Using existing prospectively collected pubertal maturation and environmental biomarker data, and recently acquired measurements of serum hormones in banked serum samples timed to maturation events, in a group of girls followed since ages 6 and 7, we will directly addresses the gaps noted in the 2013 IBCERCC report “Breast Cancer and the Environment: Prioritizing Prevention”. The impact of this proposal is to provide information that will lead to the identification of mechanisms of EDCs and targetable pathways, resulting in strategies to minimize disruption in the timing of pubertal events in girls and future risk of adverse health outcomes in adult women.