Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01126801
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 9.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Menopausal Depression	Drug: Estradiol; Other: Placebo control	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Estradiol	Drug: Estradiol; Oral estradiol 1.0 mg/day for four weeks.
Placebo Comparator: Placebo control	Other: Placebo control; Placebo control matched to estradiol tablets. Daily dosing for one month.

Outcome Measures

Primary Outcome Measures

1. Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End. [one month]

Secondary Outcome Measures

1. Improvement of Mood, Measured by the Self-rated Beck Depression Inventory (BDI) From Baseline to Study End. [one month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Hadine Joffe, MD MSc, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hadine Joffe, MD, Vice Chair for Research, Psychiatry Department, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01126801
• Other Study ID Numbers: 2009p001776
• First Posted: May 20, 2010
• Last Update Posted: Oct 20, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Hot Flashes; Estradiol

Study Results

Participant Flow

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estradiol: Oral estradiol 1.0 mg/day for four weeks.	Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month.
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Estradiol	Placebo	Total
Arm/Group Description	Estradiol: Oral estradiol 1.0 mg/day for four weeks.	Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month.	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (0)	55 (0)	52.5 (3.5)
Sex: Female, Male (Count of Participants)
Female	1 100%	1 100%	2 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End.
Time Frame	one month

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estradiol: Oral estradiol 1.0 mg/day for four weeks.	Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month.
Measure Participants	0	0

2. Secondary Outcome

Title	Improvement of Mood, Measured by the Self-rated Beck Depression Inventory (BDI) From Baseline to Study End.
Time Frame	one month

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estradiol: Oral estradiol 1.0 mg/day for four weeks.	Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Estradiol		Placebo
Arm/Group Description	Estradiol: Oral estradiol 1.0 mg/day for four weeks.		Placebo control: Placebo control matched to estradiol tablets. Daily dosing for one month.
All Cause Mortality
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

Due to the challenge of identifying eligible participants, we decided to stop enrolling subjects and not to analyze the 2 completed participants.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.