Perimenopausal Effects of Estradiol on Reward Responsiveness

Inclusion Criteria

• Perimenopause Status: We will employ the Stages of Reproductive Aging Workshop (STRAW) criteria70 to confirm perimenopausal status. The stages are primarily based on the characteristics of the menstrual cycle and secondarily on follicle stimulating hormone (FSH) levels. The anchor for the staging system is the final menstrual period (FMP). We will enroll women who have ≥ 2 skipped cycles and an interval of amenorrhea ≥ 60 days, consistent with the late menopause transition (stage -1), and who demonstrate an FSH level > 25 IU/mL. Because extremes of body weight (BMI 30 kg/m2) or a history of chronic menstrual cycle irregularity can contribute to inaccurate reproductive staging, these will serve as additional exclusion criteria;
• MDD Group Eligibility Criterion: current diagnosis of MDD with an onset associated with menstrual cycle irregularity, and no history of psychiatric illness during the 2 years before the onset of the current depressive episode as determined by the Structured Clinical Interview for DSM-IV-TR (Diagnostic and Statistical Manual-4-Text Revision) for Axis I Disorders (SCID);
• Control Group Eligibility Criterion: absence of any past or present psychiatric disorder as assessed by the SCID.

Exclusion Criteria

Patients will not be permitted to enter this protocol if they have any of the following:

• current medication use (i.e., psychotropics, anti-hypertensives, statins, hormonal preparations, or frequent use of anti-inflammatory agents (> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (< 5 times/month) use of Ambien)*;
• pregnant, breastfeeding or trying to conceive;
• FMP more than 12 months prior to enrollment;
• history of undiagnosed vaginal bleeding;
• undiagnosed enlargement of the ovaries;
• polycystic ovary syndrome;
• history of breast or ovarian cancer;
• first degree relative with ovarian cancer;
• first degree relative with premenopausal onset or bilateral breast cancer;
• 2+ first degree relatives with breast cancer (regardless of onset);
• 3+ relatives with postmenopausal breast cancer;
• abnormal finding in a provider breast exam and/or mammogram;
• known carrier of BRCA1 or 2 mutation;
• endometriosis;
• blood clots in the legs or lungs;
• porphyria;
• diabetes mellitus;
• malignant melanoma;
• Hodgkin's disease;
• recurrent migraine headaches that are preceded by aura;
• gallbladder or pancreatic disease**;
• heart or kidney disease**;
• liver disease;
• cerebrovascular disease (stroke);
• first degree relative with history of heart attack or stroke;
• current cigarette smoking;
• current suicidal ideation or psychosis;
• past suicide attempts or psychotic episodes requiring hospitalization;
• chronic depression (i.e., episode(s) lasting 3+ years);
• recurrent depression (i.e., more than 1 prior episode, not including episodes with postpartum onset)
• depressive episode(s) within 2 years of enrollment;
• self-reported claustrophobia
• peanut allergy
• all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment; **participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that are acute in nature and/or benign will be reviewed by a study physician and exclusions will be decided case-by-case. All chronic conditions will be exclusionary.