Acute Effects of Estradiol Administration on Brain Function During Fear Learning

NCT07737613 — Early Phase 1, Not yet recruiting, 30 participants, University of Arizona

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Neuroimaging Study of Fear Learning: Effects of Estrogen

Registry	NCT07737613, acronym EstroFearGen
Status	Not yet recruiting
Phase	Early Phase 1
Study type	Interventional; na, single group, masking: none, basic science
Enrollment	30 (Estimated)
Sponsor	University of Arizona (Other)
Conditions	PTSD and Trauma-related Symptoms, Cognitive Decline in Older Adults, Post Menopausal Women
Interventions	estradiol (Drug)
Dates	start 2026-08-01 (estimated), primary completion 2027-08-01 (estimated), completion 2027-12-01 (estimated), first posted 2026-07-30, last updated 2026-07-30

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Estradiol	Experimental	Drug: estradiol	single 2mg dose of estradiol by mouth

estradiol (Drug), also known as Estrace: oral 2mg tablet of estradiol

+Outcome measures

Primary outcomes

Neural Response to Fear Conditioning Task [single visit, approximately 4 hours after taking study drug]: 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-).

Secondary outcomes

Skin Conductance Response [single visit, approximately 4 hours after taking study drug]: Sweat glands activate under stress, increasing the electrical conductance of the skin. Participants will have electrodes attached on their palm to measure changes in sympathetic nervous system activity, providing an objective, physiological measure of anticipatory anxiety.
Subjective Fear and Risk Ratings [single visit, approximately 4 hours after taking study drug]: Self-report can be used to ascertain subjective fear and explicit knowledge of threat contingencies. Participants will be asked to rate of perceived risk of each displayed stimulus from 1 (no risk) to 3 (high risk), contingency learning, and aversiveness of the stimulation (1-5) during task completion in the scanner and after.

+Eligibility

Sex: Female, ages: 60 Years to any, accepts healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

* 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

+Investigators

Ashley Huggins, Principal investigator, University of Arizona