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

内分泌干​​扰化学物质暴露和女孩乳腺发育前后早期荷尔蒙环境的纵向研究

• 批准号: 9759928
• 负责人: FRANK M BIRO
• 金额: $ 25.81万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759928
• 关键词: Address; Adult; Age; Age at Menarche; Agonist; Animals; Biological Markers; Bone Density; Breast; Cadmium; Cardiovascular Diseases; Cell Proliferation; Chemical Exposure; Data; Detection; Development; Dose; Endocrine Disruptors; Endocrine system; Environment; Environmental Exposure; Epidemiology; Equation; Estradiol; Event; Exhibits; Exposure to; Female; Flavonols; Future; Gonadal Steroid Hormones; Growth; Health; Height; Hormonal; Hormones; Human; Knowledge; Lead; Link; Longitudinal Studies; Malignant Neoplasms; Mammary gland; Measurement; Measures; Menarche; Menstruation; Modeling; Obesity; Outcome; Pathway interactions; Phenotype; Physiological; Polychlorinated Biphenyls; Population; Predisposition; Prevention; Prospective Studies; Puberty; Reporting; Research Design; Resources; Risk; Sampling; Serum; Sexual Development; Statistical Methods; Structure; Testosterone; Time; Triclosan; Vagina; Woman; cohort; dehydroepiandrosterone; design; early thelarche; enterolactone; girls; innovation; malignant breast neoplasm; novel; peripubertal period; phthalates; prospective; pubertal timing; rapid growth; steroid hormone

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.

项目摘要： 内分泌暴露的纵向研究和女孩早期的荷尔蒙环境 大约在Thelarche时 内分泌干​​扰化学物质（EDC）是外源物质，暴露于马的活动 内分泌系统破坏了内源激素的生理功能。长周期 代表了对环境暴露脆弱性的发展窗口，其中EDC可能充当 激动剂或拮抗剂对内源激素。直接联系EDC和青春期的变化的证据 人口的发展远非结论性。直接将暴露与EDC的证据和 在乳房发育期间，女孩血清类固醇水平的变化几乎不存在。 先前对青春期女孩（均在我们的同伙和其他女孩）的研究报告说，暴露于某些 EDC与以后或更早的thelarche相关，而初级成绩表明EDC可能有一个 对青春期女孩中的马环境的影响。这些研究都没有研究 环境暴露与青春期事件的年龄有关。关于结构关系的知识 涉及EDC对女孩中骑马水平的直接影响，然后是后来的青春期的时间和强度 事件，例如年龄在Thelarche，年轻人的年龄，青春期的速度，峰值高度速度和高峰时代 身高，缺乏。通过测量我们的女同胞中多种环境生物标志物，我们可以 开发用于环境暴露混合的指标，并在我们的分析中使用这些指标。与我们的 前瞻性研究设计，包括直接观察青春期成熟事件和测量 在thelarche时期血清中的类固醇激素，我们可以检查EDC对EDC的影响 这些事件使用结构等效模型。我们的研究建议填补有关 接触EDCS是否直接影响青春期女孩的荷尔蒙环境以及这些如何改变 IN与青春期里程碑的年龄有关。 由于其独特的设计，该应用程序具有很高的创新性：已经对女孩进行了评估 纵向从6-7岁的年龄纵向，在Thelarche附近的时间点进行血清马龙的测量， 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 前瞻性收集的青春期成熟和环境生物标志物数据，并最近获得 在一群女孩 紧随6岁和7岁以后，我们将直接解决2013年Ibcercc报告中指出的差距“乳房 癌症与环境：预防优先级。该提案的影响是提供信息 将导致识别EDC和可靶向途径的机制，从而导致策略 最大程度地减少女孩的青春期事件时机的破坏，并在成人中遇到不良健康状况的未来风险 女性。