# Hormonal Drivers of Perimenopausal Inflammation and Mood Symptoms

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $910,241

## Abstract

Up to one third of women, up to a billion people, experience the emergence or worsening of depressive
and anxiety (mood) symptoms as their hormonal milieu shifts into perimenopause. Despite this proportion, we
still do not understand what biological changes in perimenopause contribute to the increased risk of symptoms.
Recent work suggests that perimenopause initiates a proinflammatory state and links both follicle-stimulating
hormone (FSH) and acyl-ghrelin, two peripheral hormones that can cross the blood-brain barrier, to negative
health outcomes. The roles of FSH and acyl-ghrelin extend beyond their canonical links to fertility and hunger,
respectively. FSH receptors and ghrelin receptors are observed in many tissues and cells, including immune
cells. FSH receptors are highly expressed in monocytes and FSH receptor activation stimulates proinflammatory
cytokine production. Ghrelin receptors are expressed in the efferent vagus nerve, a well-known anti-inflammatory
component of the autonomic nervous system, and acyl-ghrelin signaling increases vagal activity. Despite these
observations, the hormonal mechanisms leading to mood symptoms remain elusive because the convergent
hormonal pathways linking perimenopausal inflammation and mood symptoms have not been modeled.
 Our goal is to compare the time course of changes in FSH, estradiol, other reproductive hormones and
acyl-ghrelin with the time course of changes in inflammation and mood. The study tests a mechanistic hypothesis
in which elevated FSH and decreased acyl-ghrelin elevate proinflammatory markers through actions on
monocytes and the autonomic nervous system, and thereby increase depressive and anxiety symptoms. This
is a prospective longitudinal case-control study using a surgical menopause model, i.e. risk-reducing bilateral
salpingo-oophorectomy (BSO). Surgical menopause reduces inter-individual variation in the onset and duration
of perimenopause, thus facilitating our ability to measure associations between hormones, inflammation, and
vagal activity pre- and post-menopause. We will recruit women seeking premenopausal risk-reducing BSO and
age-matched premenopausal “controls” having non-BSO gynecological surgery. We will collect endocrine,
immune and other measures pre-surgery, one week post-surgery and monthly post-surgery up to six months.
 Aim 1 will test the hypothesis that mood symptoms change with surgical menopause and that changes
in hormones and proinflammatory markers relate to mood symptoms, specifically measuring plasma levels of
FSH, estradiol, acyl-ghrelin, progesterone, liver-enriched antimicrobial peptide 2, cytokines and adipokines in
basal plasma. Aim 2 will test the hypothesis that proinflammatory markers change with surgical menopause and
that changes in acyl-ghrelin and vagal activity (vagal reflex, heart rate variability) relate to proinflammatory
markers. Aim 3 (exploratory) will test the hypothesis that hormones relate to monocyte signaling changes with
surgica...

## Key facts

- **NIH application ID:** 10981989
- **Project number:** 1R01MH135079-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Julie A Spicer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $910,241
- **Award type:** 1
- **Project period:** 2024-08-26 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981989

## Citation

> US National Institutes of Health, RePORTER application 10981989, Hormonal Drivers of Perimenopausal Inflammation and Mood Symptoms (1R01MH135079-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10981989. Licensed CC0.

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