Can a new drug stop mood crashes after estrogen withdrawal?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

INCLUSION CRITERIA: 1. Women with a past perimenopause-related depression (within 12 years). The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-V (SCID)) at midlife in association with menstrual cycle irregularity (and possibly hot flushes and/or vaginal dryness) and in whom menopausal hormone therapy was reported to improve their depression at any time within the prior twelve years. All women participating in this protocol will be screened with psychiatric, medical, and reproductive evaluations to confirm they are in good medical health. 2. Age 45 to 65 3. Medication free (including no mood stabilizers, no sleep medication) except for the following: women on menopausal hormone therapy who will discontinue these medications at the start of this study and have their hormone therapy replaced with estradiol 100mcg per day (as described below), women who are on stable doses of thyroid replacement for at least six months prior to study enrollment, or women who occasionally take non-steroidal anti-inflammatory drugs \[NSAIDs\] or allergy medications (although we will ask women to minimize the use of these medications during the study). 4. Subjects must have consent capacity EXCLUSION CRITERIA: The following conditions will constitute contraindications to participate in this protocol: 1. Any current Axis 1 psychiatric illness or any clinically significant sleep disorder; 2. Women with histories of hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement; 3. Past history of major depression with suicidal ideation; 4. History of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis; 5. Renal disease; hepatic dysfunction; history of cholecystitis; hypertension; 6. Women with a history of carcinoma of the breast or any undiagnosed breast nodule/mass; 7. Women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding; 8. Pregnant women; sexually active women will be required to employ barrier contraceptive methods; 9. Cerebrovascular disease (stroke); 10. Recurrent migraine headaches; 11. Women who have had a hysterectomy before one year after their last menstrual period. National Institute of Mental Health (NIMH) employees/staff and their immediate family members will be excluded from the study per NIMH policy.