Effects of Hormonal Changes on Depression in Women

Ovarian Hormone Withdrawal, Anhedonia, and Reward Sensitivity in Women With Premenstrual Exacerbations of Depression: A Crossover Randomized Controlled Trial

Phase 4 Interventional University of North Carolina, Chapel Hill · NCT06610305

This study is testing if hormone treatments can help women aged 18-45 with depression feel better during their menstrual cycle by looking at how hormonal changes affect their mood.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment75 (estimated)
Ages18 Years to 45 Years
SexFemale
SponsorUniversity of North Carolina, Chapel Hill Academic / other
Locations1 site (Chapel Hill, North Carolina)
Trial IDNCT06610305 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates how hormonal fluctuations during the menstrual cycle influence mood symptoms in women aged 18-45 with major depressive disorder that worsens premenstrually. Participants will receive either hormone treatments or placebos over three menstrual cycles while completing daily mood ratings and undergoing biobehavioral testing, including EEG assessments. The study aims to determine the impact of stabilizing hormone levels on the ability to experience pleasure and reward sensitivity in these women.

Who should consider this trial

Good fit: Ideal candidates are biologically female individuals aged 18-45 with a diagnosis of major depressive disorder and self-reported worsening of symptoms during the premenstrual phase.

Not a fit: Patients who are pregnant, breastfeeding, or using hormonal contraceptives may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for women with premenstrual exacerbations of depression.

How similar studies have performed: Other studies have explored hormonal influences on mood, but this specific approach of stabilizing hormone levels in this population is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Chapel Hill, North Carolina

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive Disorderdepressionhormonepremenstrualestrogenprogesteroneperimenstrual
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.