Perimenopausal Effects of Estradiol on Reward Responsiveness
Condition: Perimenopausal Depression
MeSH terms: Depression; Depressive Disorder
Intervention: Estradiol; Progesterone
Intervention description: Participants will receive transdermal estradiol (100μg/day) for 3 weeks; Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: Female
Minimum age: 44 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Reproductive Affective Disorder; Depression; Perimenopause; Estrogen; Estradiol treatment; Mood Disorders; Estrogen Replacement Therapy; Sex Steroids; Depressive disorder; Mental Disorders; Estradiol; Hormones; Physiological effects of drugs; Reproductive Control Agents

Summary:

      Using neuroimaging, the investigator will study the effects of estrogen on mood and brain
      function in perimenopausal women either with or without depression.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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 < 18 or > 30 kg/m2) or a
             history of chronic menstrual cycle irregularity can contribute to inaccurate
             reproductive staging, these will serve as additional exclusion criteria;

          2. 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);

          3. 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:

          1. 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)*;

          2. pregnant, breastfeeding or trying to conceive;

          3. FMP more than 12 months prior to enrollment;

          4. history of undiagnosed vaginal bleeding;

          5. undiagnosed enlargement of the ovaries;

          6. polycystic ovary syndrome;

          7. history of breast or ovarian cancer;

          8. first degree relative with ovarian cancer;

          9. first degree relative with premenopausal onset or bilateral breast cancer;

         10. 2+ first degree relatives with breast cancer (regardless of onset);

         11. 3+ relatives with postmenopausal breast cancer;

         12. abnormal finding in a provider breast exam and/or mammogram;

         13. known carrier of BRCA1 or 2 mutation;

         14. endometriosis;

         15. blood clots in the legs or lungs;

         16. porphyria;

         17. diabetes mellitus;

         18. malignant melanoma;

         19. Hodgkin's disease;

         20. recurrent migraine headaches that are preceded by aura;

         21. gallbladder or pancreatic disease**;

         22. heart or kidney disease**;

         23. liver disease;

         24. cerebrovascular disease (stroke);

         25. first degree relative with history of heart attack or stroke;

         26. current cigarette smoking;

         27. current suicidal ideation or psychosis;

         28. past suicide attempts or psychotic episodes requiring hospitalization;

         29. chronic depression (i.e., episode(s) lasting 3+ years);

         30. recurrent depression (i.e., more than 1 prior episode, not including episodes with
             postpartum onset)

         31. depressive episode(s) within 2 years of enrollment;

         32. self-reported claustrophobia

         33. 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.