Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women

Mass General Brigham

Status and phase

Terminated

Phase 2

Conditions

Menopausal Depression

Treatments

Other: Placebo control

Drug: Estradiol

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01126801

2009p001776

Details and patient eligibility

About

This protocol is a controlled study of estradiol therapy in early postmenopausal women with and without frequent hot flashes that will be used to determine whether hot flashes are an important intermediary in the generation of menopause-associated depression.

Full description

SPECIFIC AIMS (Research Objectives)

To define the relative effects of hot flashes and changes in estradiol on mood in postmenopausal women:

Hypotheses:

Estrogen treatment has a similar therapeutic effect on mood in women with and without frequent hot flashes
Estradiol levels correlate with improvement in mood

Enrollment

2 patients

Sex

Female

Ages

40+ years old

Volunteers

Accepts Healthy Volunteers

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