Impact of Life Course Socioeconomic Status on the Ovarian Reserve

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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.