# Transcriptomic signatures of menopause across human tissues

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $80,750

## Abstract

SUMMARY
An important aging milestone for women is menopause. Unfortunately, postmenopausal women have increased
coronary heart disease, stroke, and mortality risk after menopause. This can be partially attributed to increases
in cardiovascular disease (CVD) risk factors that many women experience after menopause, such as blood
pressure, lipid levels, and adiposity, but the mechanisms behind these and other changes are poorly understood.
A reduction in circulating estrogen levels is one of the major changes with menopause, and estrogen can
transcriptionally regulate many genes, often in a tissue-specific manner. Prior studies of changes in gene
expression with menopause have been limited, and most have been focused on breast, bone, and female
reproductive tissues. We hypothesize that transcriptomic examination of cardiometabolic tissues across the
menopause transition will reveal insight into the molecular processes responsible for the increased CVD risk.
Though menopause status information is missing from most human tissue gene expression datasets, we
hypothesize that menopausal status can be inferred from gene expression data. To accomplish this, in Aim 1A
we will infer the menopausal status of hundreds of female Genotype-Tisssue Expression (GTEx) subjects based
on the gene expression profiles of their female reproductive tissues, using a combination of dimensionality
reduction approaches informed by known biology and more agnostic, clustering-based methodology. Since the
average GTEx subject contributed samples from over 18 tissues, we will have inferred menopausal status
information for non-reproductive tissues as well. In a preliminary analysis of uterus gene expression data
(withholding age as a covariate), we observed clear classification of individuals into an inferred premenopausal
(age<54) and an inferred postmenopausal group (age>48). Since menopause status is confounded by age, in
Aim 1B we will identify sex-specific aging genes and examine the relationship of gene expression with
chronological age in each sex subset. In Aim 1C, we will use the inferred menopausal status information from
Aim 1A to identify genes and pathways that are differentially expressed in tissues derived from inferred
premenopausal versus postmenopausal women, focusing on cardiometabolic tissues of relevance to
cardiovascular disease, such as liver, adipose, and blood vessels. Inferred menopause-related genes that do
not exhibit similar correlations with chronological age in male tissues are likely to be regulated by the female-
specific hormonal changes during menopause rather than more general aging processes. Overall, this will be
the most comprehensive evaluation of the effects of menopause on gene expression performed to date, and the
findings could identify molecular pathways underlying the increased disease burden in post-menopausal women.

## Key facts

- **NIH application ID:** 10352100
- **Project number:** 1R03AG075466-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elizabeth Theusch
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,750
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352100

## Citation

> US National Institutes of Health, RePORTER application 10352100, Transcriptomic signatures of menopause across human tissues (1R03AG075466-01). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10352100. Licensed CC0.

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