# The impact of exogenous estradiol on fear extinction in healthy young women and those with PTSD

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $38,424

## Abstract

PROJECT SUMMARY
For this F31 proposal, the applicant will build upon their current skills to determine the influence of estradiol (E2)
during the early luteal phase of the menstrual cycle on neural correlates of fear extinction in women with and
without Post Traumatic Stress Disorder (PTSD). Women are twice as likely as men to be diagnosed with PTSD,
and those with PTSD are more likely to have fear extinction impairments. Natural fluctuations of E2 have been
associated with an increase in anxiety, depression, and PTSD symptoms in women during the early luteal phase,
when there is a sharp decrease in E2, and it has been shown women with PTSD have the greater fear extinction
deficits during the early- to mid-luteal phase, compared to the early follicular phase. Fear extinction is strongly
suspected to be regulated by the ventral medial prefrontal cortex (vmPFC), with fear conditioning regulated by
the amygdala. Both low E2 levels and PTSD are individually correlated with reduced vmPFC blood-oxygenation-
level-dependent (BOLD) activity and lower functional connectivity between the vmPFC and amygdala. However,
we do not yet know how E2 administration impacts fear extinction and BOLD activity in women with and without
PTSD during the early luteal phase. Given prior findings, we hypothesize that E2 administration during the early
luteal phase will increase fear extinction compared to placebo. To test this central hypothesis, we will utilize
functional magnetic resonance imaging (fMRI) of the vmPFC and amygdala to determine how exogenous E2
during the early luteal phase impacts fear extinction in healthy women (Aim 1). We will then determine the effects
of exogenous E2 on fear extinction during the luteal phase in women with PTSD compared to controls (Aim 2).
vmPFC Region of Interest (ROI) analysis and functional connectivity analysis will be utilized for Aim 1 and 2,
with skin conductance utilized as a measure of psychophysiological fear conditioning. To explore extinction-
related plasticity within the vmPFC and amygdala, we will perform multivariate pattern analysis on the collected
fMRI data from control and PTSD participants (Exploratory Aim 3). Prior literature has shown patterns of
activation within the vmPFC differentiate those with PTSD and controls. This will provide a test of the causal
influence of E2 on fear extinction in women during the early luteal phase when E2 sharply declines, providing
support for the idea that withdrawal from E2 produces fear extinction deficits and can negatively impact PTSD
symptoms. Such findings may provide an avenue of future possible treatment for women who have experienced
traumatic events. In order to gain expertise in neuroimaging, neuroendocrinology, psychophysiology, and clinical
research, the applicant’s training will include a combination of mentored research from a team of experts in these
fields and a visit to another lab studying trauma and PTSD, as well as coursework, seminars, and attendance at
nat...

## Key facts

- **NIH application ID:** 10687876
- **Project number:** 5F31MH126623-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Alyssa Rose Roeckner
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $38,424
- **Award type:** 5
- **Project period:** 2021-09-02 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687876

## Citation

> US National Institutes of Health, RePORTER application 10687876, The impact of exogenous estradiol on fear extinction in healthy young women and those with PTSD (5F31MH126623-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10687876. Licensed CC0.

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