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Estrogen for Treating Depression in Menopausal Women With Hot Flashes and Insomnia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00227942
Recruitment Status : Completed
First Posted : September 28, 2005
Last Update Posted : May 26, 2014
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Hadine Joffe, MD, Massachusetts General Hospital

Brief Summary:
This study will evaluate the effectiveness of estrogen replacement therapy in treating depression in menopausal women with hot flashes and insomnia.

Condition or disease Intervention/treatment Phase
Sleep Initiation and Maintenance Disorders Depression Drug: Estrogen Replacement Therapy Drug: Zolpidem Drug: placebo Phase 4

Detailed Description:

Estrogen is a hormone that plays an important part in the development of the female reproductive system. During menopause, estrogen levels drop significantly. The drop in estrogen may cause physiologic and psychological changes in women; common symptoms include hot flashes, sweating, insomnia, and irritability. In addition, approximately 10% of menopausal women experience depression. Estrogen replacement therapy (ERT) is often prescribed to alleviate these symptoms. It is not known, however, exactly how ERT treats depression. It may indirectly decrease depression by alleviating insomnia associated with hot flashes, or it may directly improve mood and decrease depression by altering chemicals in the brain. The purpose of this study is to gain insight into how ERT treats depression and to develop strategies to reduce depression in menopausal women. In turn, these findings may help categorize populations of women whose depression should be treated with ERT versus nonhormonal therapies.

In this 9-week study, participants will be randomly assigned to receive ERT, a sleeping pill, or placebo. Study visits will occur at baseline and Weeks 2, 4, 6, and 9; at each study visit, blood pressure will be monitored, and standardized psychological tests and questionnaires will be used to assess the participant's level of depression and reported quality of life outcomes. Blood will be drawn at baseline and Week 9 to measure estrogen and follicle stimulating hormone levels.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Understanding the Role That Hot Flashes and Sleep Disruption Play in the Effect of Estrogen Replacement Therapy on Mood in Perimenopausal and Postmenopausal Women
Study Start Date : August 2003
Actual Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Participants will receive estrogen replacement therapy
Drug: Estrogen Replacement Therapy
17-b-Estradiol Patch, .05 mg/day; applied for 7 days
Other Name: Climara

Experimental: 2
Participants will receive treatment with zolpidem
Drug: Zolpidem
10 mg/day, po qhs
Other Name: Ambien

Placebo Comparator: 3
Participants will receive treatment with placebo
Drug: placebo

Primary Outcome Measures :
  1. Improvement of mood; measured by the Montgomery-Asberg Depression Rating Scale [ Time Frame: Measured at at baseline and Weeks 2, 4, 6, and 9 ]

Secondary Outcome Measures :
  1. Quality of life indicators; measured by the Quality of Life Inventory [ Time Frame: Measured at at baseline and Weeks 2, 4, 6, and 9 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Perimenopausal or postmenopausal status
  • Surgical menopause or hysterectomy with one or both ovaries preserved if serum follicle stimulating hormone is greater than 20 IU/L
  • Diagnosed with mild to moderate clinical depression
  • Currently experiencing moderate to severe hot flashes
  • Currently experiencing insomnia caused by nocturnal hot flashes
  • Normal mammogram within the 2 years prior to study entry
  • Willing to use an effective form of contraception throughout the study if perimenopausal and sexually active

Exclusion Criteria:

  • Current severe depression or history of severe depression within the 5 years prior to study entry
  • Suicidal or homicidal ideation
  • Psychotic symptoms
  • History of any psychiatric disorder (e.g., psychosis, bipolar disorder, panic disorder, obsessive-compulsive disorder, or anorexia nervosa)
  • History of any substance abuse (including alcohol abuse) within the 5 years prior to study entry
  • Regular use of hormonal medications within the month prior to study entry
  • Regular use of hypnotic drugs, antidepressants, or over-the-counter drugs known to influence hot flashes, sleep, or mood within the 2 weeks prior to study entry
  • Intolerance to estrogen therapy or informed that estrogen therapy is medically inadvisable

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00227942

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United States, Massachusetts
MGH Center for Perinatal and Women's Mental Health
Boston, Massachusetts, United States, 02116
Sponsors and Collaborators
Hadine Joffe, MD
National Institute of Mental Health (NIMH)
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Principal Investigator: Hadine Joffe, MD, MSC Massachusetts General Hospital
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hadine Joffe, MD, Director of Research at the Center for Women's Mental Health, Massachusetts General Hospital Identifier: NCT00227942    
Other Study ID Numbers: K23MH066978 ( U.S. NIH Grant/Contract )
K23MH066978 ( U.S. NIH Grant/Contract )
First Posted: September 28, 2005    Key Record Dates
Last Update Posted: May 26, 2014
Last Verified: May 2014
Keywords provided by Hadine Joffe, MD, Massachusetts General Hospital:
Hot flash
Sleep Disruption
Estrogen Replacement Therapy
Additional relevant MeSH terms:
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Sleep Initiation and Maintenance Disorders
Hot Flashes
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
GABA-A Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action