# Changes in cardiometabolic tissue gene regulation and omics profiles with menopause

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $450,688

## Abstract

SUMMARY
The menopausal transition is a time of extensive hormonal and physiological changes for women in midlife.
Unfortunately, it is often accompanied by a worsening of cardiovascular and metabolic disease risk factors, such
as increases in plasma cholesterol levels, central adiposity, and blood pressure, and women have greater
coronary heart disease, stroke, and mortality risk after menopause. To date, scientists only have a limited
understanding of the molecular level changes that are set into motion as ovarian follicle supplies dwindle and
estradiol levels fall with menopause, especially in non-reproductive tissues. We hypothesize that extensive,
tissue-specific transcriptomic changes occur during and after the menopausal transition, leading to metabolic
reprogramming in cardiometabolic tissues. Here, our first aim will be to use a chemically-induced, ovarian follicle
depletion mouse model of the menopausal transition to identify menopause-induced changes in chromatin
accessibility and gene expression in mouse liver, adipose, and aorta tissues. In addition to “menopausal” female
and control-treated male and female (estrous cycling) mice, there will also be groups of “menopausal” mice
implanted with estradiol versus placebo tubing. This experiment will allow comparisons between female follicle-
depleted (“menopausal”) and cycling mice, between follicle-depleted mice implanted with E2 and control tubing,
between female cycling mice at distinct stages of the estrous cycle (high E2 vs. low E2), and between male and
female mice. Our second aim is to identify elements of women’s omics profiles associated with menopause
status and time since menopause. To do this, we will compare transcriptomic, metabolomic, and proteomic
profiles between premenopausal and postmenopausal women in studies with enough premenopausal and
postmenopausal samples. Completion and integration of these aims will help to identify factors driving the
increase in cardiovascular disease risk during the menopausal transition, their downstream targets, and the
impact of estradiol hormone therapy on reversal of the changes. Clinically, this could help to optimize the timing
and type of interventions that could be used in the future to control cardiovascular disease risk in midlife women.

## Key facts

- **NIH application ID:** 10872907
- **Project number:** 1R21AG086775-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elizabeth Theusch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $450,688
- **Award type:** 1
- **Project period:** 2024-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872907

## Citation

> US National Institutes of Health, RePORTER application 10872907, Changes in cardiometabolic tissue gene regulation and omics profiles with menopause (1R21AG086775-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10872907. Licensed CC0.

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