Impact of Life Course Socioeconomic Status on the Ovarian Reserve

描述（由申请人提供）：2007年至2020年间，美国绝经后妇女的数量将增加30%，在短短13年的时间里，每年增加100多万妇女。绝经的时间是绝经后健康和死亡率的关键决定因素。特别是，绝经年龄较早与心血管疾病风险增加有关，包括缺血性心脏病、中风、动脉粥样硬化和心脏特异性死亡率，这些因素共同占绝经后妇女发病率和死亡率的很大比例。在这方面，阐明解释更年期时间变化的因素是至关重要的，因为它提出了通过专门针对更年期延迟和/或改善其后遗症的干预努力来改变这些因素的可能性。对研究更年期开始的预测因素的文献回顾显示，越来越多的研究发现，较低的社会经济地位（SES）与提前绝经有关，甚至独立于其他已知的加速生殖衰老的风险因素，如吸烟。绝经时间作为结果的检查明显有限；然而，由于更年期的定义是回顾性的，在此之后，时间干预是不可能的。为了解决这一局限性并扩展现有文献，拟议的研究将转而研究“卵巢衰老”的变异性，即卵巢功能丧失导致月经永久停止（即更年期）的生物学过程。具体来说，本研究的目标是研究女性环境的各个方面，包括1)在整个生命过程和特定发育时期（童年、青春期和成年期）测量的社区水平的社会经济地位，以及2)与卵巢衰老有关的选定环境毒物（通常聚集在低社会经济地位环境中）。这些关联将在现有的基于社区的978名25-45岁的绝经前妇女队列中进行检验，这些妇女是OVA研究（2006-2011）的参与者，这是一项横断面调查，通过完善的卵巢总储备生物标志物来评估卵巢衰老，包括窦卵泡计数（AFC）和抗苗勒管激素（AMH）。NIH的资金将支持从公开可用的数据集中提取与sds相关的环境暴露变量，并与现有的OVA研究数据集合并，以评估更大的社区社会经济劣势和对选定毒物的暴露增加的历史是否可能加速卵巢储备的消耗，如较低的AFC和AMH水平所示。本研究的结果将为卵巢加速衰老及其后遗症的预测因素的识别和指导提供新的见解

DESCRIPTION (provided by applicant): The number of post-menopausal US women will rise by 30% between years 2007 and 2020, an increase of more than 1 million women per year over a period of just 13 years. The timing of menopause is a key determinant of post-menopausal health and mortality. In particular, earlier age at menopause is associated with an increase in cardiovascular risk for outcomes including ischemic heart disease, stroke, atherosclerosis, and cardiac-specific mortality which together account for a significant proportion of morbidity and mortality among women in the post-menopausal period. In this regard, elucidating factors that explain variability in the timing of menopause is of critical importance as it raises the possibiliy that such factors may be modified through intervention efforts specifically targeting the delay of menopause and/or the amelioration of its sequelae. Review of the literature examining predictors of menopausal onset shows a growing number of studies have found lower socioeconomic status (SES) is prospectively related to earlier menopausal onset, even independently of other well-established risk factors for accelerated reproductive aging such as cigarette smoking. The examination of menopausal timing as an outcome is significantly limited; however, as menopause by definition is determined retrospectively after which time intervention is not possible. To address this limitation and extend the current literature, the proposed study will instead examine variability in "ovarian aging", the biological process underlying the loss of ovarian function leading to the permanent cessation of menses (i.e., menopause). Specifically, the goals of the proposed study are to examine aspects of women's environments, including 1) neighborhood-level SES, measured over the life course and in particular developmental periods (childhood, puberty, and adulthood) as well as 2) selected environmental toxicants (that commonly cluster in low SES environments) in relation to ovarian aging. These associations will be examined in an existing, community-based cohort of 978 pre-menopausal women ages 25-45 who were participants in the OVA Study (2006-2011), a cross-sectional investigation that assessed ovarian aging as indexed by well- established biomarkers of total ovarian reserve, including antral follicle count (AFC) and anti-Mullerian hormone (AMH). NIH funding will support the extraction of SES-related and environmental exposure variables from publically available datasets to be merged with the existing OVA Study dataset in order to evaluate whether histories of greater neighborhood-level socioeconomic disadvantage and increased exposure to selected toxicants may accelerate the depletion of the ovarian reserve as indexed by lower AFC and AMH levels. Results from the current study will provide new insights into the identification of predictors of accelerated ovarian aging and its sequelae and in pointing to new avenues for screening and intervention among at-risk women.