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

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

Eligibility

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.

Conditions2

Locations1 site

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