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Impact of Hot Flashes on Sleep and Mood Disturbance

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2014 by Hadine Joffe, MD, Massachusetts General Hospital.
Recruitment status was:  Active, not recruiting
ClinicalTrials.gov Identifier:
First Posted: May 5, 2010
Last Update Posted: April 15, 2014
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.
Information provided by (Responsible Party):
Hadine Joffe, MD, Massachusetts General Hospital

We plan to enroll 60 healthy, non-pregnant premenopausal women age 18-45 who do not have hot flashes (in order to have 30 women complete all study procedures) in a trial investigating the impact of hot flashes developed in response to an injection of a GnRH agonist, leuprolide (brand name: Lupron) on sleep disruption and mood. This study is designed to mimic the menopause transition. Based on previous studies, we expect that 2/3 of the women will develop hot flashes, naturally dividing participants into two groups: + hot flashes and no hot flashes. We will collect data on sleep disruption and mood changes to compare differences between the + hot flashes group and the group of women who do not develop hot flashes on leuprolide.

Specific Aim 1: To determine the effects of hot flashes on sleep using a model of induced hot flashes in pre-menopausal women.

Hypothesis 1a: Hot flashes worsen objectively measured sleep

Hypothesis 1b: Exposure to hot flashes leads to the perception of poor sleep quality

Specific Aim 2: To identify the relative effects of hot flashes and sleep disruption on mood using a model of induced hot flashes in premenopausal women.

Hypothesis 2a: Objectively measured sleep disturbance has a greater effect than hot flashes on mood

Hypothesis 2b: Perception of poor sleep correlates with negative mood

Exploratory Aim: To establish the feasibility of identifying specific genetic polymorphisms for genes involved in the estrogen pathway and the development of hot flashes.

Condition Intervention
Menopause Depression Hot Flashes Drug: Leuprolide

Study Type: Interventional
Study Design: Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Impact of Experimentally Induced Hot Flashes on Sleep and Mood Disturbance

Resource links provided by NLM:

Further study details as provided by Hadine Joffe, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in sleep efficiency from pre- to post-GnRH agonist administration [ Time Frame: Two PSG studies at baseline and two PSG studies at study end, 4 weeks after GnRH agonist administration ]
    Sleep efficiency will be calculated by averaging the two PSG studies at each time point.

Secondary Outcome Measures:
  • Average daily number of subjectively reported hot flashes (hot flash diary) [ Time Frame: 4th week after GnRH agonist is given ]

Estimated Enrollment: 50
Study Start Date: October 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GnRH Agonist Injection
We will be administering an injection of leuprolide acetate (a GnRH agonist) to all participants.
Drug: Leuprolide

Leuprolide acetate 3.75-mg intramuscular injection

Leuprolide is a widely used GnRH agonist. Leuprolide is indicated for treatment of endometriosis, uterine fibroids, precocious puberty, and prostate cancer, and is used off-label for in-vitro fertilization and premenstrual syndrome. In this protocol, leuprolide will be administered at a dose routinely used for treatment of endometriosis and uterine fibroids in women.

Leuprolide can induce amenorrhea for 2-3 months after a depot injection is given. However, unpredictable menstrual bleeding and spotting can occur during this time period. Menstrual-cycle patterns will be monitored closely during the study. Although long-term administration of any GnRH agonist (i.e., >6 months) is associated with bone loss, bone effects are not expected in this protocol because GnRH agonist therapy will be used for only one month.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Women 18-45 years old
  • Premenopausal, defined as regular monthly menstrual cycles (every 25-35-days) for the past 6 months and corroborated by a mid-luteal phase progesterone of > 3 ng/ml
  • Willingness to use barrier methods of contraception during study and after completion of study until menses resume
  • Good general health with normal hemoglobin, prolactin, TSH, liver function tests (SGOT, SGPT, bilirubin) and renal function tests (BUN, creatinine, alkaline phosphatase)

Exclusion Criteria:

  • Pregnancy, as determined by serum HCG at screening visit and immediately preceding (day before or day of) GnRH agonist administration, or currently breastfeeding.
  • Hot flushes, as determined subjectively (7-day hot flash diary) and objectively (24-hour skin-conductance monitoring
  • Mid-luteal phase progesterone <3ng/mL
  • Clinically significant abnormalities in screening blood tests.
  • BMI > 35 kg/m2
  • Previously diagnosed osteoporosis or osteopenia
  • Clinically significant depressive symptoms (Montgomery-Asberg Depression Rating Scale (MADRS) score > 10)
  • Psychiatric illness, as defined by clinical interview and the Mini-International Neuropsychiatric Interview (MINI).
  • Sleep apnea or periodic limb movement of sleep (PLMS) either diagnosed previously or on a screening polysomnography (PSG) study.
  • Contraindication, hypersensitivity, or previous allergic reaction to GnRH agonists
  • Current or recent (one month) use of centrally active medications (antidepressants, anxiolytics, hypnotics, or the anticonvulsant gabapentin.
  • Current or recent (3 months) use of systemic hormone medications
  • Night shift workers
  • Current or recent (one month) over-the-counter (OTC) medications that may affect hot flashes, sleep, or mood (eg diphenhydramine, St. John's Wort, Black Cohosh, and other phytoestrogen supplements)
  • Abnormal vaginal bleeding
  • History of any medical diseases that may put subject at risk when treated with study medication. These include a history of thrombo-embolism or cardiovascular disease, congestive heart failure or other conditions requiring sodium restriction, spinal cord compression, metastatic vertebral lesions, memory disorders, urinary tract obstruction or history of liver, kidney, pulmonary, or metabolic disease that may put subject at risk when treated with study medication.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01116401

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Hadine Joffe, MD
Principal Investigator: Hadine Joffe, MD Massachusetts General Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hadine Joffe, MD, Director of Research at the Center for Women's Mental Health, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01116401     History of Changes
Other Study ID Numbers: 2009-P-001557
First Submitted: May 3, 2010
First Posted: May 5, 2010
Last Update Posted: April 15, 2014
Last Verified: April 2014

Keywords provided by Hadine Joffe, MD, Massachusetts General Hospital:
Hot Flashes
Sleep disturbance

Additional relevant MeSH terms:
Hot Flashes
Signs and Symptoms
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action