# Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes

> **NIH NIH U54** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $1,772,835

## Abstract

Older women experience dramatic changes in the hypothalamic-pituitary-gonadal (HPG) axis and female
reproductive hormones, producing vasomotor symptoms (VMS), sleep problems, cognitive changes, and
cardiometabolic risks, which increase susceptibility to cardiovascular disease (CVD) and dementia. VMS occur
in 85% of women and persist in one-third for 10+ years after menopause, potentially leading to prolonged
disruption of quality of life, sleep disturbance, cardiometabolic risk, and extended VMS treatment, conferring
further risk for CVD and dementia. Such health outcomes may also be influenced by stress exposures across
the lifespan and during pregnancy, which may exert their effects through neural mechanisms. Brigham and
Women’s Hospital (BWH) and Harvard Medical School (HMS) seek to establish a SCORE to advance our
understanding of stress exposures and neural regulation of reproductive aging health outcomes, and to
catalyze growth of translational women’s health and sex-differences research in aging women. We will pursue
novel translational science through three Projects: Project 1 (Joffe/Mahon; clinical science) will define evoked
stress responsivity, stress-related activation of neural networks on functional brain imaging, and GABA
concentrations as markers of VMS occurrence and persistence, including compounding effects of poor sleep
and stress exposures. Project 2 (Oken/Chavarro; population science) will determine whether perimenopausal
women with higher exposure to social stressors across the lifespan and physiological stressors across
pregnancy have greater cardiometabolic risk, sleep, cognitive, and neuropsychiatric symptoms. Project 3
(Kaiser/Navarro; basic science) will characterize the role of kisspeptin, neurokinin, and dynorphin (KNDy)
neurons and upstream GABAergic neurons in mediating the effects of stress and corticosteroids on the HPG
axis, VMS, and sleep disturbances in a rodent model. These scientific efforts will receive critical support from
our Cores: The Sleep Resource Core (Klerman) will extend our scientific impact by investigating sleep
outcomes in humans and rodents. The Career Enhancement Core (Rexrode/Rich-Edwards) will promote early-
career and new sex-differences investigators by supporting Scholars, Pilot Projects, Travel Exchange
Fellowships, and a robust educational program. The Leadership Administrative Core (Joffe/Manson) will
provide scientific and administrative oversight and engage with the SCORE Consortium. Building on existing,
fruitful collaborations, our outstanding interdisciplinary team of investigators—leaders in women’s health, sleep
medicine, neuroimaging, neuroendocrinology, stress science, cognition, cardiometabolic, and reproductive
epidemiology—will leverage robust resources at the Connors Center for Women’s Health and Gender Biology
and across synergistic women’s health and sleep programs at BWH. This SCORE will produce a significant
public health impact by advancing our understanding of the ...

## Key facts

- **NIH application ID:** 9854034
- **Project number:** 1U54AG062322-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** HADINE JOFFE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,772,835
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854034

## Citation

> US National Institutes of Health, RePORTER application 9854034, Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes (1U54AG062322-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854034. Licensed CC0.

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