Menopausal Sleep Fragmentation and Body Fat Gain

Study Overview
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Brief Summary
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This study aims to investigate the impact of menopause-related sleep fragmentation on metabolic biomarkers of body fat gain. The investigators hypothesize that experimental sleep fragmentation will result in an adverse leptin response as a metabolic biomarker for body fat gain.

Detailed Description
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While obesity is highly prevalent in midlife and older women, with rates increasing markedly after age 40 and body fat increasing in half of women during and after the menopause transition, factors causing these changes are not well understood. Reduced total sleep time has been shown to adversely impact biomarkers of obesity, but the effect of the highly prevalent menopause-related sleep fragmentation secondary to hot flashes on metabolism and eating behaviors in humans is not known. We will use experimental paradigms to isolate the impact of menopause-related sleep disruption, as well as that of hot flashes and estrogen withdrawal, metabolic biomarkers of body fat gain and on eating behaviors, results of which will inform strategies to prevent body fat gain and improve cardio-metabolic health outcomes in women.

Official Title
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Menopausal Sleep Fragmentation: Impact on Body Fat Gain Biomarkers in Women

Conditions
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Menopause

Intervention / Treatment
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* Drug: Estradiol withdrawal
* Other: Fragmented sleep


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy premenopausal women 18-45 years old Regular sleep schedule Limited alcohol and caffeine intake Regular monthly menstrual cycles No lifetime history of hot flashes Willingness to use approved methods of contraception during study Not obese Good general health Exclusion Criteria: Contraindication, hypersensitivity or previous adverse reaction to gonadotropin releasing hormone agonists Pregnancy Breastfeeding Tobacco use Contraindicated systemic hormone medications or centrally active medications Shift workers or recent/expected time zone travel Obstructive sleep apnea Insomnia symptoms Diagnosis of osteoporosis or osteopenia Hypothalamic-pituitary-adrenal axis disorders Diabetes Gastric bypass, metabolic disorders, or other related conditions Abnormalities on screening laboratory tests Substantial hearing impairment Cardiovascular illness Neurological illness Recent psychiatric illness or substance-use disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep fragmentation - active<br>Participants after 3 nights of experimentally-fragmented sleep | Other: Fragmented sleep<br>* Fragmented sleep will be experimentally induced.<br>|
| No Intervention: Sleep fragmentation - control<br>Participants after 2 nights of unfragmented sleep | |
| Experimental: Estradiol withdrawal - active<br>Participants after experimentally-induced hypo-estradiol | Drug: Estradiol withdrawal<br>* one injection of open-label intramuscular dose of leuprolide (3.75-mg depot), a gonadotropin-releasing hormone agonist that rapidly suppresses estradiol and temporarily achieves ovarian suppression.<br>* Other names: Leuprolide Acetate; Lupron;|
| No Intervention: Estradiol withdrawal - control<br>Participants during high-estradiol phase of menstrual cycle | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leptin | serum leptin levels | 12-hour overnight fasted morning sample | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satiety | subjective satiety measured by visual analog scale, 0 (low) - 100 (high) | 12-hour overnight fasted morning sample | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep fragmentation, menopause, leuprolide, adipokine, weight gain, leptin