This trial is active, not recruiting.

Conditions menopause, depression, hot flashes
Treatment leuprolide
Sponsor Hadine Joffe, MD
Start date October 2009
End date June 2014
Trial size 50 participants
Trial identifier NCT01116401, 2009-P-001557


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model factorial assignment
Masking open label
Primary purpose basic science
We will be administering an injection of leuprolide acetate (a GnRH agonist) to all participants.
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.

Primary Outcomes

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

Secondary Outcomes

Average daily number of subjectively reported hot flashes (hot flash diary)
time frame: 4th week after GnRH agonist is given

Eligibility Criteria

Female participants from 18 years up to 45 years old.

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.

Additional Information

Official title Impact of Experimentally Induced Hot Flashes on Sleep and Mood Disturbance
Principal investigator Hadine Joffe, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.