Recruiting

Ovarian Hormone Withdrawal

Sponsor:

University of North Carolina, Chapel Hill

Code:

NCT06610305

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: Female

Age: 18 - 45

Healthy Volunteers: Not accepted

Interventions

Transdermal estradiol

Progesterone

Transdermal placebo patch

placebo capsule

Study Details

Brief summary:

The goal of this clinical trial is to learn how hormonal changes over the menstrual cycle affect mood symptoms in reproductive-aged women with depression that worsens during the premenstrual period. The main questions it aims to answer are:

--How do fluctuations in estradiol and progesterone across the menstrual cycle affect the ability to experience pleasure and the neural sensitivity to reward in hormone-sensitive, depressed women? And consequently, how does stabilizing the luteal phase decline in estrogen and progesterone (using estradiol patches and progesterone pills) affect these changes?

Participants will:

  • Receive hormones followed by placebo, or vice versa, for a total of four weeks across three menstrual cycles
  • Complete daily mood ratings
  • Collect home urine samples for hormone testing
  • Complete five biobehavioral testing sessions during which neural responses are recorded (via electroencephalography, or EEG) during an acute stress task and computer tasks

Conditions

Major Depressive Disorder

Study ID

NCT06610305

Start date

Sep 2, 2024

Status verified date

Oct, 2025

Completion date

Jun 1, 2028

Anticipated

Primary completion date

Jun 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 45

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Biologically female and between the ages of 18-45 years (45 set as upper limit to avoid endocrine changes associated with perimenopause).
  • Self-reported regular menstrual cycles between 25 and 35 days.
  • A previous diagnosis of major depressive disorder, with self-reported premenstrual worsening of symptoms.
  • If the woman has children, she must be at least 1 year postpartum.
  • English-speaking

Exclusion Criteria:

  • Pregnant, breastfeeding, or trying to become pregnant. Pregnancy status will be confirmed using a urine pregnancy test at the enrollment visit and again at the first visit of the second condition. Women will be instructed to use a barrier method of birth control during the study.
  • Taking any form of exogenous hormones or IUD, and must have ended previous use of hormonal preparations at least one month prior to the study. Women who were previously taking oral contraceptives or other hormonal medications must have one normal menstrual cycle (menstrual period) prior to enrollment in the study.
  • BMI less than 18 or greater than 29.
  • A personal history of any chronic medical condition that could confound the experimental protocol, including but not limited to metabolic or autoimmune disease, epilepsy, endometriosis, cancer, diabetes, cardiovascular, gastrointestinal, hepatic, renal, pulmonary disease, migraine with aura, hypertension, Parkinson's disease, chronic pain, and thromboembolic events.
  • A family history indicative of increased risk of breast cancer or thromboembolic disorders.
  • Current cigarette smoking.
  • A history of mania, psychosis, or substance use disorder.
  • Any recent history (last 12 months) of active suicidal ideation, or suicide attempt within the last 5 years.

Study Design

Enrollment

75 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Estradiol+Progesterone, then Placebo

Two weeks of luteal phase transdermal estradiol (0.1mg/day)+oral progesterone (200 mg/day) during the first intervention cycle, followed by a one cycle washout, followed by two weeks of luteal phase transdermal/oral placebo

experimental: Placebo, then Estradiol+Progesterone

Two weeks of luteal phase transdermal/oral placebo during the first intervention cycle, followed by a one cycle washout, followed by two weeks of luteal phase transdermal estradiol (0.1 mg/day)+oral progesterone (200 mg/day)

Interventions

Transdermal estradiol

0.1 mg/day delivered via weekly patch

Progesterone

100 mg twice daily (200 mg/day total) administered via oral capsule

Transdermal placebo patch

Once weekly via transdermal patch

placebo capsule

Twice daily via oral capsule

Primary outcome measure

  • Dimensional Anhedonia Rating Scale (Luteal Phase Stabilized vs Luteal Phase Unstabilized Hormones vs Follicular Phase) [ Time Frame: 3 menstrual cycles (each cycle approximately 28 days in duration) ]
  • Reward Positivity (Luteal Phase Stabilized vs Luteal Phase Unstabilized Hormones vs Follicular Phase) [ Time Frame: Over the course of 2 menstrual cycles (~28 days each), EEG will be collected four times on four separate days: twice during the late luteal phase (11-14 days following ovulation), and twice during the mid follicular phase (23-25 days following ovulation) ]

Central Contacts and Locations

Central contacts

Study Coordinator

(919) 445-6814pearstudy@unc.edu

Locations

University of North Carolina, Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27707

Contacts

Study Coordinator

(919) 445-6814pearstudy@unc.edu

More Information

Sponsor

University of North Carolina, Chapel Hill

Last update posted

Oct 29, 2025

Last verified

Oct, 2025

Keywords

  • depression
  • hormone
  • premenstrual
  • estrogen
  • progesterone
  • perimenstrual

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of North Carolina, Chapel Hill on 2025-10-29.