Ovarian Hormone Withdrawal, Anhedonia, and Reward Sensitivity in Women With Premenstrual Exacerbations of Depression

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

NCT Number	NCT06610305
Lead Sponsor	University of North Carolina, Chapel Hill Collaborators: National Institute of Mental Health (NIMH)
Conditions	Major Depressive Disorder
Enrollment	75 participants
Start Date	2024-09-02
Primary Completion	2028-06-01 (estimated)
Study Completion	2028-06-01 (estimated)
Updated on ClinicalTrials.gov	2025-10-29