Menopausal Sleep Fragmentation and Body Fat Gain

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Study arm	Estradiol withdrawal	Participants completed 2 nights of unfragmented sleep followed by 3 nights of experimentally-fragmented sleep during high estradiol (E2) phase of their menstrual cycle (Sleep Block 1). A subset of participants repeated these procedures in an experimentally-induced low-E2 state (Sleep Block 2).
Study arm	Fragmented sleep	Participants completed 2 nights of unfragmented sleep followed by 3 nights of experimentally-fragmented sleep during high estradiol (E2) phase of their menstrual cycle (Sleep Block 1). A subset of participants repeated these procedures in an experimentally-induced low-E2 state (Sleep Block 2).

Primary Outcome Measures

Name	Time	Method
Normalized Serum Leptin Levels	pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks)	12-hr overnight fasted AM (morning) blood samples were assayed for leptin levels on study days 2-6 under both estrogenized and estradiol-withdrawal conditions \[total: 10 samples\]. For each individual, leptin values were normalized relative to the mean baseline leptin value. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition).

Secondary Outcome Measures

Name	Time	Method
Normalized Satiety Scores	pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks)	12-hr overnight fasted AM satiety scores were collected on study days 2-6 under both estrogenized and estradiol-withdrawal conditions \[total: 10 scores\]. For each individual, satiety scores were normalized relative to the mean baseline satiety score. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition).