# Effects of hormones and menopausal transitions on hippocampal structure and function

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $156,000

## Abstract

ABSTRACT
 Age-related changes in hormone levels occur in both men and women but are more pronounced in women
approaching menopause, typically between the ages of 45 to 52 years old 1. Despite prior data addressing
brain-aging differences in women and men, how hormone changes in midlife affect brain structure and
cognition in women remains unclear. Women appear to be more vulnerable to cognitive decline during this
peri-menopausal period 2, and there is general agreement that women experience memory deficits during this
timeframe 3–6. Estrogen-depletion is widely regarded as a likely cause of cognitive impairment in peri-menopausal women 7 but the mechanistic understanding of how declining estrogen rates affect cognitive
decline and brain changes is relatively poorly understood. In animal models, estrogen receptors are found
throughout the brain, but predominate in limbic-related areas that play a crucial role in cognitive function 8.
Specifically, these animal studies show hippocampal subfields Cornu Ammonis 1, 2, and 3 as densely
populated regions of estrogen-receptors; activation of these estrogen-receptors has been shown to mediate
estrogen's beneficial effect on synaptic plasticity as well as play a role in preventing neurodegeneration in
hippocampal neurons 9,10.
 We propose here investigating the impact of declining estrogen levels on hippocampal structure
and function in peri-menopausal women as part of our collaboration with the Human Connectome Project-
Aging (HCP-A). This project makes use of the rigorously structured data collection pipeline HCP-A is using to
objectively stage menopause data points. Although the data detailed here are being collected as part of the
HCP-A project, with 103 subjects currently available and an additional 107 anticipated to be recruited over the
coming 2 years, no support for subsequent investigations is included as part of the HCP-A; investigations
proposing to answer scientific questions using the dataset must be funded with separate research
support. Specifically, we will analyze high-field magnetic resonance imaging (MRI) data of the
hippocampus in order to assess memory structures and function in fine detail and determine whether
lower estrogen levels predict poorer memory performance in peri-menopausal women. We will also
investigate whether hormone replacement therapy has a beneficial effect at mediating the effect of changes in
estrogen levels in midlife women. We expect results from this project to shed light on the complex
relationship between changes in hormone levels and subsequent effects on hippocampal structure and
memory function in midlife.

## Key facts

- **NIH application ID:** 9903187
- **Project number:** 5R21AG061758-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ALISON CLEMENTS BURGGREN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903187

## Citation

> US National Institutes of Health, RePORTER application 9903187, Effects of hormones and menopausal transitions on hippocampal structure and function (5R21AG061758-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903187. Licensed CC0.

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