# Stress response and neural network function in women with vasomotor symptoms

> **NIH NIH U54** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $402,071

## Abstract

The broad goal of Project 1 of the Brigham/Harvard SCORE Center for Stress and Neural Regulation of
Reproductive Aging Health Outcomes is to advance the health of postmenopausal women by determining stress
responsivity in vasomotor symptoms (VMS) occurrence and persistence and to characterize neural processes
and neurobiological mechanisms linking VMS with stress responsivity. VMS are the most common symptoms
during and after menopause, occurring in up to 85% of women, lasting 7.4–9.0 years on average, and persisting
for 10+ years in 33–40% of postmenopausal women. Investigations of stress mechanisms underlying VMS have
important public health significance due to their high prevalence, impact on quality of life, and adverse health
correlates. VMS disrupt sleep and are associated with cardiometabolic disease, which, together with risks of
hormone therapy used to treat VMS, increase susceptibility to dementia in aging women. We propose a novel
conceptualization of VMS as a chronic stress condition based on our preliminary data and that of others indicating
associations of stress responsivity with VMS. Differences in responsivity to evoked stress tasks in women with
VMS suggest underlying disruptions in stress-related neural networks (e.g., anterior cingulate cortex,
hippocampus, orbitofrontal cortex, insula) and in the inhibitory neurotransmitter gamma-aminobutyric acid
(GABA), which regulates stress networks, as is seen in chronic stress conditions (e.g., anxiety, pain).
Dysregulated stress responses may reflect neural processes through which stress mediates VMS. Project 1 will
innovatively combine the robust methodology of an evoked stress paradigm with state-of-the-art functional
magnetic resonance imaging and magnetic resonance spectroscopy to cross-sectionally investigate acute stress
responsivity, neural network function, and GABA concentrations in women with and without VMS referred by
Project 2 (Project Viva cohort). We will determine longitudinally whether dysregulation of neural stress networks
and GABA predict persistence of VMS over a 2-year follow-up period. In conjunction with the Sleep Resource
Core (SRC), we will examine whether sleep disruption comorbid with VMS further blunts acute stress
responsivity. Similarly, we will test whether perceived stress contributes differentially to stress response
dysregulation in those with VMS. Project 1 is integrated within the Brigham/Harvard SCORE, through enrolling
participants and obtaining relevant longitudinal data from the Project 2 cohort, examining mechanistic neural
stress processes underlying VMS in parallel with Project 3, utilizing sleep metrics obtained by the SRC, and
teaching and mentoring junior faculty and trainees through the Career Enhancement Core. Leveraging these
synergistic SCORE and extensive Brigham/Harvard institutional resources, our study will make major
contributions to the health of aging women by identifying neural stress mechanisms linked to VMS—potentially
pointi...

## Key facts

- **NIH application ID:** 10424523
- **Project number:** 5U54AG062322-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** HADINE JOFFE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,071
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424523

## Citation

> US National Institutes of Health, RePORTER application 10424523, Stress response and neural network function in women with vasomotor symptoms (5U54AG062322-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10424523. Licensed CC0.

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