Depression, Hot Flashes, Menopause
Conditions
Keywords
Hot Flashes, Sleep disturbance, Lupron, Menopause
Brief summary
We plan to enroll premenopausal women in a trial investigating the impact of hot flashes developed in response to an injection of a gonadotropin-releasing hormone agonist (GnRHa), leuprolide (brand name: Lupron), on sleep disruption and mood. This study is designed to mimic the menopause transition. We will collect data on sleep disruption and mood changes to assess their relationship to the development of hot flashes.
Interventions
DRUGleuprolide
Leuprolide acetate is a widely used GnRH agonist. In this protocol, leuprolide will be administered at a dose routinely used for treatment of endometriosis and uterine fibroids in women (one 3.75-mg intramuscular injection).
Sponsors
National Institute of Mental Health (NIMH)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Women 18-45 years old * Premenopausal * Willingness to use barrier methods of contraception during study and after completion of study until menses resume * Good general health
Exclusion criteria
* Pregnancy or currently breastfeeding * Hot flushes * 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 * Psychiatric illness * Sleep apnea or periodic limb movement of sleep (PLMS) * Contraindication, hypersensitivity, or previous allergic reaction to GnRH agonists * Current or recent use of centrally active medications * Current or recent use of systemic hormone medications * Night shift workers * Current use of over-the-counter (OTC) medications that may affect hot flashes, sleep, or mood * Abnormal vaginal bleeding * History of any medical diseases that may put subject at risk when treated with study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Wake After Sleep Onset (WASO) | baseline and 4 weeks | Wake after sleep onset (WASO) is calculated by averaging the number of minutes spent awake after initiating sleep each night from the two ambulatory polysomnography studies conducted at baseline and the two ambulatory polysomnography studies conducted four weeks after the GnRHa injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asperg Depression Rating Scale (MADRS) | baseline and 4 weeks | The Montgomery-Åsberg Depression Rating Scale is a widely used 10-item clinician-rated scale that describes the severity of depressive symptoms. It has a range of 0-60 with higher scores indicating greater symptom burden. Participants were assessed at baseline and four weeks after the GnRHa injection in order to calculate the change in MADRS score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GnRH Agonist Injection One 3.75-mg intramuscular injection of leuprolide acetate | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | GnRH Agonist Injection |
|---|---|
| Age, Continuous | 27.3 years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Percent Change in Wake After Sleep Onset (WASO)
Wake after sleep onset (WASO) is calculated by averaging the number of minutes spent awake after initiating sleep each night from the two ambulatory polysomnography studies conducted at baseline and the two ambulatory polysomnography studies conducted four weeks after the GnRHa injection.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GnRH Agonist Injection | Percent Change in Wake After Sleep Onset (WASO) | 62 percent change |
p-value: 0.007Regression, Linear
Secondary
Change in Montgomery-Asperg Depression Rating Scale (MADRS)
The Montgomery-Åsberg Depression Rating Scale is a widely used 10-item clinician-rated scale that describes the severity of depressive symptoms. It has a range of 0-60 with higher scores indicating greater symptom burden. Participants were assessed at baseline and four weeks after the GnRHa injection in order to calculate the change in MADRS score.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GnRH Agonist Injection | Change in Montgomery-Asperg Depression Rating Scale (MADRS) | 3.1 units on a scale | Standard Deviation 5.4 |
p-value: <0.01Regression, Linear