Clinical trial NCT01126801: Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women
Official title: Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Menopausal Depression
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2010-05-20
Enrollment: 2
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End.
timeFrame: one month
Secondary outcomes:
measure: Improvement of Mood, Measured by the Self-rated Beck Depression Inventory (BDI) From Baseline to Study End.
timeFrame: one month
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Hadine Joffe, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Galvan T, Camuso J, Sullivan K, Kim S, White D, Redline S, Joffe H. Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study. Menopause. 2017 Jan;24(1):112-117. doi: 10.1097/GME.0000000000000737.