Menopausal Sleep Fragmentation and Body Fat Gain

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Menopause

Treatments: Other: Fragmented sleep; Drug: Estradiol withdrawal

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03047330

2016P002821

1R01AG053838 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

41 participants in 1 patient group

Study arm

Experimental group

Description:

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).

Treatment:

Drug: Estradiol withdrawal

Other: Fragmented sleep