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NCT Number: NCT07737613

Acute Effects of Estradiol Administration on Brain Function During Fear Learning

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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Key information

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Estradiol

Drug

oral 2mg tablet of estradiol

Other names: Estrace

Primary outcomes

  1. Neural Response to Fear Conditioning Task

    Time frame: 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

  1. Skin Conductance Response

    Time frame: 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.

  2. Subjective Fear and Risk Ratings

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Nancy Huynh

CONTACT

[email protected]

520-333-5482

Sponsors and collaborators

Lead sponsor

University of Arizona

Other

Registry information

Official study title

Neuroimaging Study of Fear Learning: Effects of Estrogen

Acronym: EstroFearGen

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 30, 2026
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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