Menopausal Depression
Conditions
Brief summary
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.
Detailed description
SPECIFIC AIMS (Research Objectives) To define the relative effects of hot flashes and changes in estradiol on mood in postmenopausal women: Hypotheses: 1. Estrogen treatment has a similar therapeutic effect on mood in women with and without frequent hot flashes 2. Estradiol levels correlate with improvement in mood
Interventions
DRUGEstradiol
Oral estradiol 1.0 mg/day for four weeks.
OTHERPlacebo control
Placebo control matched to estradiol tablets. Daily dosing for one month.
Sponsors
National Institutes of Health (NIH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End. | one month |
Secondary
| Measure | Time frame |
|---|---|
| Improvement of Mood, Measured by the Self-rated Beck Depression Inventory (BDI) From Baseline to Study End. | one month |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estradiol Estradiol: Oral estradiol 1.0 mg/day for four weeks. | 1 |
| Placebo Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Estradiol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 0 | 55 years STANDARD_DEVIATION 0 | 52.5 years STANDARD_DEVIATION 3.5 |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End.
Time frame: one month
Population: No participants were analyzed since the study was terminated due to difficulty recruiting subjects. Because data from only one subject per arm were collected, these data are not reported to preserve subject privacy.
Secondary
Improvement of Mood, Measured by the Self-rated Beck Depression Inventory (BDI) From Baseline to Study End.
Time frame: one month
Population: No participants were analyzed since the study was terminated due to difficulty recruiting subjects. Because data from only one subject per arm were collected, these data are not reported to preserve subject privacy.