# Longitudinal Evaluation of Ovarian Aging and Cardiovascular Risk

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $1,209,568

## Abstract

ABSTRACT
Despite significant improvements in prevention and treatment of cardiovascular disease (CVD), the growing
aging population suggests CVD will continue to pose a significant public health burden. Women are a special
group where microvascular disease is more common and traditional risk factors may not fully identify risk.
Women's reproductive history (e.g. menarcheal age, menstrual cycles, infertility, pregnancy, menopause) may
pose unique risk and suggests an opportunity for new approaches. We propose a women-centered approach
for early identification of women at risk that investigates the unique loss of reproductive function at an age
long before other vital systems fail. Despite the importance of this process, little is known about the
determinants or correlates of ovarian aging, or the health implications, especially in diverse populations. With
reliable bio-markers of the remaining oocyte pool available, we have a unique opportunity to characterize the
association between “ovarian age” and the health implications of accelerated oocyte loss. We hypothesize a
risk independent of the well-known impact of early menopause and estrogen deficiency. Rather, we
propose that common underlying cellular aging mechanisms, first evident in the ovary due to its sensitivity
and earlier demise, make the ovary a window on underlying somatic health. Confirming an association
between a decline in markers of ovarian age and CVD risk would allow a potentially high-risk population to
be identified decades before traditional risk factors develop. The Ovarian Aging (OVA) cohort is the largest
and most ethnically diverse, community-based cohort available that can be used to determine the
race/ethnic and behavioral determinants of ovarian aging and its association with CVD risk in a young cycling
population. To assess the relationship between markers of ovarian age (reflecting past exposures and genetic
risk), the rate of ovarian aging (representing current exposures) and CVD risk, we propose to: 1. Determine
whether markers of ovarian age/aging are associated with increased CVD risk by testing if ovarian
age/aging is independently associated with increased CVD risk, as measured by peripheral endothelial
function testing; 2. Determine whether ovarian aging may moderate or mediate established associations
between race/ethnicity and/or socio/emotional health and CVD risk by examining whether observed race/ethnic
disparities, or effects of socio/emotional health, on CVD risk, may vary by (moderation model) or be partially
attributable to (mediation model) ovarian aging; and 3. Determine whether ovarian aging, CVD risk, and the
temporal pattern of appearance correlate with markers of cellular aging: telomere length and mtDNA in
peripheral leukocytes, oxidative stress (plasma F2α-isoprostanes), and indices of inflammation (C-reactive
protein, interleukin- 6, and soluble intercellular adhesion molecule-1). Overall Impact: Our novel longitudinal
approach to evaluating ...

## Key facts

- **NIH application ID:** 10441072
- **Project number:** 5R01AG053332-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MARCELLE Ivonne CEDARS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,209,568
- **Award type:** 5
- **Project period:** 2017-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441072

## Citation

> US National Institutes of Health, RePORTER application 10441072, Longitudinal Evaluation of Ovarian Aging and Cardiovascular Risk (5R01AG053332-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10441072. Licensed CC0.

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