| Criteria: |
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Inclusion Criteria:
- Healthy women ≥40 years-old
- Early postmenopausal, defined as:
- No menstrual bleeding for 12-60 months secondary to natural menopause, according to
STRAW criteria48
- Hysterectomy without bilateral oöphorectomy if surgery was completed after 6+ months
of amenorrhea (no maximum duration of amenorrhea required)
- Bilateral oöphorectomy (no minimum or maximum duration of amenorrhea required)
- Serum follicle-stimulating hormone (FSH) >25 IU/L and estradiol <20 pg/ml
- Diagnosis of major depression on the MINI
- Mild-to-moderate depressive symptoms, as indicated by MADRS score 15-31 and BDI score
>15
- Normal mammogram within the past 2 years
- Good general health
Exclusion Criteria:
- Severe depression, defined as a MADRS score >31, psychotic symptoms, or suicidal or
homicidal ideation
- Psychiatric illness, as defined by clinical interview and the Mini-International
Neuropsychiatric Interview (MINI), as:
- A lifetime history of bipolar disorder
- A lifetime history of severe depression, as characterized by current or prior
psychotic symptoms, inpatient psychiatric hospitalization or a suicide attempt
in the previous 5 years, or
- Current panic disorder or obsessive compulsive disorder
- A lifetime history of psychotic symptoms
- Current anorexia nervosa
- An alcohol or substance-use disorder active within the past year
- Current suicidal or homicidal ideation
- Previous diagnosis of a sleep disorder (sleep apnea, PLMS, etc) or diagnosed on a
screening PSG study
- Pregnant, confirmed with serum ß-HCG at baseline (Visit 1)
- Breastfeeding
- Contraindication, hypersensitivity, or previous adverse reaction to E2 therapy
- Current or recent (1 month) use of centrally active medications (antidepressants,
anxiolytics, hypnotics, anticonvulsants, stimulants)
- Current or recent (2 months) use of systemic hormone medications
- History of breast cancer, premalignant breast lesions, or undiagnosed breast mass
- Vaginal spotting or bleeding
- History of thrombo-embolism, cardiovascular disease, congestive heart failure or
other contraindication to estradiol therapy.
- Liver dysfunction or disease
- Renal insufficiency
- Contraindications to progestin therapy
- Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable and
under medical management
- Other medical contraindications to estradiol and progestin therapy including
porphyria, systemic lupus erythematosus, hepatic hemangiomas, deep vein thrombosis,
hereditary angioedema, hypertriglyceridemia, severe Hypocalcemia.
- Clinically significant abnormalities in screening blood tests including:
- Thyroid-stimulating hormone <0.50 or >5.0 uU/mL)
- Shift workers |