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Estradiol for Depression and Psychosis in Perimenopausal Women

This study is looking at how estradiol affects the brain and symptoms of depression and psychosis in women going through perimenopause. Researchers believe that lower estradiol levels during this time might contribute to anhedonia (loss of pleasure) and psychosis by impacting brain reward systems. You would be given either a transdermal estradiol patch (100μg/day) or a matching placebo patch for three weeks. All participants will also receive two PET-MR scans using Raclopride C11 to measure brain activity. At the end of the study, you'll receive micronized progesterone (200 mg/day) for one week. The study aims to see if estradiol changes brain activity related to reward. This study is for women aged 45-55 who are unmedicated and in late perimenopause, with skipped menstrual cycles or amenorrhea. The study plans to enroll 103 participants, but its current status is unclear.

Study design
This is an interventional study planning to enroll 103 women. Participants will be randomly assigned to receive either transdermal estradiol or a placebo patch.
What's involved
You would receive a transdermal patch for three weeks, followed by one week of micronized progesterone. You would also have two PET-MR scans, one at the beginning and one after three weeks of treatment.
Compensation
Not stated in the trial record.
Follow-up
The primary endpoint is measured from baseline to week 7, suggesting follow-up for at least that duration.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05282277

Examining the Effects of Estradiol on Neural and Molecular Response to Reward

Recruiting
PHASE4Ages 45–55InterventionalTreatment
University of North Carolina, Chapel Hill
~103 participants
Updated 2026-04-29 on ClinicalTrials.gov
What's tested:Transdermal EstradiolMicronized ProgesteroneMatching Placebo PatchRaclopride C11

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Changes in Striatal Activation Between Groups during the MID task
Measured over Baseline (week 3) to Endpoint (week 7)

Conditions

Depression
Psychosis
Anhedonia

Explore related trials

AnhedoniaDepressionPerimenopausalPsychosis

Where it's being run

1 sites across 1 states
North Carolina1

Study leadership

  • Crystal E Schiller, PhD · PRINCIPAL_INVESTIGATOR · UNC School of Medicine - Department of Psychiatry
  • Gabriel Dichter, PhD · PRINCIPAL_INVESTIGATOR · UNC School of Medicine - CIDD

Who to contact

Kathryn G Gibson, BS
[email protected]
919-966-5243
Email the study team

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Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

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Eligibility criteria

Inclusion

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures, lifestyle considerations, and availability for the duration of the study
44-55 years old unmedicated perimenopausal women who have ≥ 2 skipped menstrual cycles, amenorrhea ≥ 60 days, corresponding to the late menopause transition (Stages of Reproductive Aging Workshop (STRAW stage -1).
Anhedonia or psychosis symptoms that began during the period of menstrual irregularity.
Clinician's Global Impression Scale-Severity score (CGI-S) \> 3 to confirm a clinically impaired sample.
Willingness to adhere to the estradiol regimen

Exclusion

Pregnancy; allergies to any active or inactive ingredients in the Climara® patch or Prometrium®.
BMI \< 18 or \> 35 kg/m\^2
A history of chronic menstrual cycle irregularity, meaning \> 1 year without menses
MR contraindications: Metal in the body, dental work other than fillings or gold, tattoos, metal injury, any other implant unless they are 100% plastic.
PET contradictions: participation in \>1 research study in the past 12 months that included ionizing radiation exceeding 3 rem to the whole body (e.g., PET, CT). Standard of care imaging is not exclusionary.
The use of psychotropics or hormonal preparations.
History of psychiatric illness during the 2 years before the onset of perimenopause.
History of chronic, recurrent mood or psychotic disorders (i.e., more than one non-reproductive-related mood episode prior to the perimenopausal index episode).
A history of mood episodes requiring hospitalization.
Current mania;
Depressive episode(s) within 2 years of enrollment not associated with the transition to menopause;
A history of suicide attempts within the last year or current active suicidal ideation with intent and plan.
Neurological conditions (e.g., history of seizure or TBI)
Brain stimulation treatment in the past six months.
Endometriosis;
First degree relative with premenopausal breast cancer or breast cancer presenting in both breasts or multiple family members (greater than three relatives) with postmenopausal breast cancer.
Current medication use (i.e., current psychotropics, current anti-hypertensives, current statins, current hormonal preparations, or frequent use of anti-inflammatory agents (\> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (\< 5 times/month) use of Ambien)\*;
Pregnant, breastfeeding or trying to conceive;
Last menstrual period more than 12 months prior to enrollment;
History of undiagnosed vaginal bleeding;
Undiagnosed enlargement of the ovaries;
Polycystic ovary syndrome;
History of breast or ovarian cancer;
First degree relative with ovarian cancer;
Abnormal finding in a provider breast exam and/or mammogram;
Known carrier of BRCA1 or 2 mutation;
Porphyria;
Malignant melanoma;
Hodgkin's disease;
Recurrent migraine headaches that are preceded by aura;
Gallbladder or pancreatic disease\*\*;
Heart or kidney disease\*\*;
Liver disease;
cerebrovascular disease (stroke);
First degree relative with history of heart attack or stroke;
Current nicotine use;
Self-reported claustrophobia
Peanut allergy
all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment;
participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that are acute in nature and/or benign will be reviewed by a study physician and exclusions will be decided case-by-case. All chronic conditions will be exclusionary. For those where it is deemed that an exclusion does not apply, primary analyses will not be affected, but exploratory analyses will be conducted excluding these individuals

What this trial measures

  • Changes in Striatal Activation Between Groups during the MID taskBaseline (week 3) to Endpoint (week 7)

    Characterize reward-related striatal activation measured by fMRI using the Monetary Incentive Delay (MID) task to elicit blood-oxygen-level dependent (BOLD) responses. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) response to win trials versus non-win trials. Reactivity is then compared between the two groups.