Acute Effects of Estradiol Administration on Brain Function During Fear Learning

NCT07737613 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: STUDY00008306
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of current study is to better understand how fear is processed in the brain and how these processes are influenced by cognition and hormones. This research will focus specifically on postmenopausal female adults, because age-related changes in cognition and declining estrogen levels may contribute to anxiety symptoms and PTSD risk later in life.

Conditions

PTSD and Trauma-related Symptoms; Cognitive Decline in Older Adults; Post Menopausal Women

Outcome Measures

Primary Outcomes (1)

• Neural Response to Fear Conditioning Task

  Estrogen has been shown to modulate the function of brain regions involved in fear processing, including the amygdala, hippocampus, and ventromedial prefrontal cortex. During fMRI, participants will complete a fear conditioning and generalization task to measure brain activity. They will view different neutral images of geometric shapes which may or may not predict the imminent receipt of an electric shock to the ankle. Across voxels of the brain, activation estimates (BOLD response) will be extracted for CS+ (conditioned threat) vs. CS- (conditioned safety) cues, and linear activation patterns across ambiguous generalization stimuli (i.e., GSs; CS+ \> GS1 \> GS2 \> GS3 \> CS-).

  single visit, approximately 4 hours after taking study drug

Secondary Outcomes (2)

• Skin Conductance Response

  single visit, approximately 4 hours after taking study drug

• Subjective Fear and Risk Ratings

  single visit, approximately 4 hours after taking study drug

Study Arms (1)

Estradiol

EXPERIMENTAL

single 2mg dose of estradiol by mouth

Drug: estradiol

Interventions

estradiol DRUG

oral 2mg tablet of estradiol

Also known as: Estrace

Estradiol

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• post-menopausal
• normal or corrected-to-normal vision
• English speaking
• stable medication use (no changes in the past three months)

You may not qualify if:

• use of hormone therapy containing synthetic estrogen
• MRI contraindications (e.g., irremovable ferrous metal in body, claustrophobia)
• history of neurological disorder (including mild cognitive impairment) or moderate to severe traumatic brain injury
• use of antipsychotic, opiate, or mood stabilizer (i.e., lithium) medication
• history of blood clots/deep vein thrombosis, prior stroke or TIA, uncontrolled hypertension
• history of migraine with aura
• severe liver disease
• history of breast, endometrial, or ovarian cancer
• smoking \>10 cigarettes/day

Sponsors & Collaborators

• University of Arizona: lead

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Ashley Huggins

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy Huynh

CONTACT

520-333-5482; nxhuynh@arizona.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share