Impact of Life Course Socioeconomic Status on the Ovarian Reserve

描述(申请人提供)：2007年至2020年，美国绝经后女性的数量将增加30%，在短短13年的时间里，每年增加100多万女性。绝经时间是绝经后健康和死亡率的关键决定因素。特别是，更年期较早的年龄与心血管风险的增加有关，包括缺血性心脏病、中风、动脉粥样硬化和心脏特有的死亡率，这些因素加在一起，在绝经后妇女的发病率和死亡率中占很大比例。在这方面，阐明解释更年期时间变化的因素至关重要，因为它增加了通过专门针对推迟更年期和/或改善其后遗症的干预努力来改变这些因素的可能性。回顾研究绝经开始的预测因素的文献表明，越来越多的研究发现，较低的社会经济地位(SES)可能与较早的绝经开始有关，甚至与吸烟等其他公认的加速生殖衰老的危险因素无关。对绝经时间作为结果的检查受到极大的限制；然而，由于绝经的定义是追溯确定的，在此之后不可能进行干预。为了解决这一局限性并扩展目前的文献，拟议的研究将转而研究“卵巢老化”的可变性，“卵巢老化”是导致卵巢功能丧失导致永久停止月经(即更年期)的生物学过程。具体地说，这项研究的目标是检查女性环境的各个方面，包括1)社区水平的SES，在整个生命过程中，特别是在发育阶段(儿童、青春期和成年期)测量，以及2)选定的环境毒物(通常聚集在低SES环境中)与卵巢衰老的关系。这些相关性将在现有的社区队列中进行检验，978名年龄在25-45岁的绝经前女性参与了OVA研究(2006-2011年)，这是一项横断面调查，以成熟的总卵巢储备生物标志物为指标评估卵巢老化，包括腔卵泡计数(AFC)和抗米勒激素(AMH)。NIH的资金将支持从公开可用的数据集提取SES相关和环境暴露变量，并将其与现有的OVA研究数据集合并，以评估社区层面更大的社会经济劣势和更多暴露于选定毒物的历史是否会加速以较低的AFC和AMH水平为指标的卵巢储备的耗竭。目前的研究结果将为识别卵巢加速老化及其后遗症的预测因素提供新的见解 到在高危妇女中进行筛查和干预的新途径。

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.