Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women

NCT ID: NCT01126801

Last Updated: 2017-10-20

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2011-02-28

Brief Summary

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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

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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

Conditions

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Menopausal Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Estradiol

Group Type EXPERIMENTAL

Estradiol

Intervention Type DRUG

Oral estradiol 1.0 mg/day for four weeks.

Placebo control

Group Type PLACEBO_COMPARATOR

Placebo control

Intervention Type OTHER

Placebo control matched to estradiol tablets. Daily dosing for one month.

Interventions

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Estradiol

Oral estradiol 1.0 mg/day for four weeks.

Intervention Type DRUG

Placebo control

Placebo control matched to estradiol tablets. Daily dosing for one month.

Intervention Type OTHER

Eligibility 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 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
Minimum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Hadine Joffe, MD

Vice Chair for Research, Psychiatry Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hadine Joffe, MD MSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 27648659 (View on PubMed)

Other Identifiers

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2009p001776

Identifier Type: -

Identifier Source: org_study_id