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

项目概要： 女孩内分泌干扰化学品暴露和早期激素环境的纵向研究 乳房初长时期 内分泌干扰物（EDCs）是一种外源性物质， 内分泌系统，扰乱内源性激素的生理功能。青春期前期 代表了易受环境暴露影响的发育窗口，在该窗口中，内分泌干扰物可能作为 内源激素的激动剂或拮抗剂。证据直接链接内分泌干扰物和青春期的改变 人类的发展还远远没有定论。有证据直接将暴露于内分泌干扰物和 女孩在乳房发育前后血清类固醇激素水平几乎没有变化。 以前对青春期女孩的研究（包括我们的队列和其他队列）报告说， 内分泌干扰物与晚或早的乳房初潮和月经初潮有关，这表明内分泌干扰物可能具有 对青春期女孩荷尔蒙环境的影响。这些研究中没有一项研究探讨了 环境暴露与青春期年龄有关。关于结构关系的知识 关于EDCs对女孩激素水平的直接影响，以及青春期后期的时间和强度， 事件，如乳房初潮年龄、月经初潮年龄、青春期节奏、高峰身高速度和高峰年龄 高度，缺乏。通过测量我们女孩队列中的多种环境生物标志物，我们可以 开发环境暴露混合物的指标，并在我们的分析中使用这些指标。与我们 前瞻性研究设计，包括直接观察青春期成熟事件和测量 在乳房发育前后，我们可以检查暴露于内分泌干扰物对 这些事件使用结构方程模型。我们的研究建议填补知识上的差距， 暴露于内分泌干扰物是否对青春期女孩的激素环境有直接影响，以及这些变化如何 与青春期里程碑的年龄有关。 这个应用程序是高度创新的，因为其独特的设计：女孩已经评估 从6-7岁纵向，在乳房发育前后的时间点进行血清激素测量， 和青春期前环境生物标志物的测量。我们的假设是新颖的。使用现有 前瞻性地收集青春期成熟和环境生物标志物数据，最近获得 在一组女孩中，测量与成熟事件定时的库存血清样本中的血清激素 从6岁和7岁开始，我们将直接解决2013年IBCERCC报告“乳房”中指出的差距， 癌症与环境：优先预防”。这项建议的影响是提供信息， 将导致识别内分泌干扰物的机制和有针对性的途径，从而制定策略， 最大限度地减少女孩青春期事件的时间中断和成年人未来不良健康后果的风险 妇女

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.