Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women

This is an interventional treatment trial for Menopausal Depression Read More

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 oophorectomy if surgery was completed after 6+ months of amenorrhea (no maximum duration of amenorrhea required)
• Bilateral oophorectomy (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