Actively Recruiting

Phase 4
Age: 45Years - 55Years
FEMALE
ID05282277

Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

Led by University of North Carolina, Chapel Hill · Updated on 2026-04-29

103

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

Sponsors

U

University of North Carolina, Chapel Hill

Lead Sponsor

N

National Institute of Mental Health (NIMH)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are studying the effects of estradiol on symptoms of anhedonia and psychosis that begin during perimenopause, the transition to menopause. The study aims to understand how estradiol influences brain function and dopamine activity in reward processing using combined PET and fMRI brain imaging. This research focuses on women experiencing these symptoms during late perimenopause and explores the role of declining estradiol levels in these conditions. Participants will be randomly assigned to receive either a transdermal estradiol patch (100 mcg/day) for three weeks followed by one week of combined estradiol and micronized progesterone (200 mg/day) or a matching placebo patch for three weeks. The study uses a double-blind, placebo-controlled design with groups balanced by severity of anhedonia and psychosis symptoms. All participants will have two PET-MR scans using [11C]raclopride to measure dopamine function and brain responses to reward before and after treatment. Throughout the study, participants will complete clinical assessments of anhedonia and psychosis symptoms, including scales like the Snaith-Hamilton Pleasure Scale and the Brief Psychiatric Rating Scale. Brain imaging with PET-MR will track changes in striatal activation and dopamine release during reward tasks. The primary outcome is the change in striatal activation during a monetary incentive delay task from baseline to study endpoint. Safety and adherence to the estradiol regimen will be monitored during the approximately seven-week study period.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 45Years - 55Years
FEMALE

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed and dated informed consent form
  • Willingness to comply with all study procedures, lifestyle considerations, and availability for study duration
  • Women aged 44 to 55 years in late perimenopause with at least 2 skipped menstrual cycles or 60 days of amenorrhea
  • Presence of anhedonia or psychosis symptoms that began during menstrual irregularity
  • Clinician's Global Impression Scale-Severity score greater than 3
  • Snaith-Hamilton Pleasure Scale (SHAPS) score greater than 20 indicating clinically impairing anhedonia
  • Stratification by psychosis severity using the Brief Psychiatric Rating Scale (BPRS)
  • Willingness to follow the estradiol treatment regimen
Not Eligible

You will not qualify if you...

  • Pregnancy or breastfeeding, or trying to conceive
  • Allergies to ingredients in Climara4 or Prometrium4 patches
  • Body mass index less than 18 or greater than 35 kg/m82
  • History of chronic menstrual irregularity lasting more than 1 year
  • Contraindications to MRI or PET imaging, including metal implants or recent high radiation exposure
  • Use of psychotropic or hormonal medications
  • Psychiatric illness within 2 years before perimenopause onset
  • History of recurrent mood or psychotic disorders unrelated to reproductive episodes
  • Mood episodes requiring hospitalization
  • Current mania or depressive episodes unrelated to menopause transition
  • Recent suicide attempts or active suicidal thoughts
  • Neurological disorders such as seizures or traumatic brain injury
  • Brain stimulation treatment in past 6 months
  • Endometriosis
  • Family history of premenopausal breast cancer or multiple postmenopausal breast cancer cases
  • Current use of medications with mood effects, except stable thyroid replacement or rare use of Ambien
  • Last menstrual period more than 12 months ago
  • Undiagnosed vaginal bleeding or ovarian enlargement
  • Polycystic ovary syndrome
  • History of breast or ovarian cancer, or BRCA1/2 mutation carrier
  • Abnormal breast exam or mammogram
  • Porphyria, malignant melanoma, Hodgkin's disease
  • Recurrent migraine with aura
  • Gallbladder, pancreatic, heart, kidney, liver, or cerebrovascular disease
  • Family history of heart attack or stroke
  • Current nicotine use
  • Claustrophobia
  • Peanut allergy
  • Any acute or chronic medical conditions as determined by study physician review before enrollment

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 4 weeks

Participants receive 3 weeks of transdermal estradiol or matching placebo patches, followed by 1 week of combined transdermal estradiol and micronized progesterone to induce menstruation.

2 PET-MR scan visits (baseline and post treatment), plus additional visits for medication administration and assessments

Follow-up

Duration - Up to the end of week 7 (approximately 3 weeks post-treatment)

Participants are monitored for changes in symptoms and neural responses after completion of the treatment phase.

Visits coincide with post-treatment assessments

Trial Site Locations

Total: 1 location

1

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27514

Actively Recruiting

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Research Team

K

Kathryn G Gibson, BS

L

Laura C Lundegard, BA

How is the study designed?

Study Type

INTERVENTIONAL

Masking

DOUBLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

8

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Published Research Related To This Trial

Depressive symptoms during the menopausal transition: the Study of Women's Health Across the Nation (SWAN).

Joyce T Bromberger, Karen A Matthews, Laura L Schott...

https://pubmed.ncbi.nlm.nih.gov/17331589

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

Gabriel S Dichter, Cara A Damiano, John A Allen

https://pubmed.ncbi.nlm.nih.gov/22958744

Reduced frontostriatal response to expected value and reward prediction error in remitted monozygotic twins with mood disorders and their unaffected high-risk co-twins.

Julian Macoveanu, Iselin Meluken, Henry W Chase...

https://pubmed.ncbi.nlm.nih.gov/32115012