The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The study will determine whether the stress hormone cortisol contributes to this shift.
The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The stress hormone cortisol is known to promote the accumulation of belly fat, and there is evidence that low estrogen is associated with higher cortisol levels. The first aim of the study is to determine whether low estrogen levels in premenopausal and early postmenopausal women increase cortisol levels in the blood and in fat tissue. When estrogen level decreases at the time of menopause, there is an increase in follicle-stimulating hormone, or FSH. Recent evidence in mice suggests that blocking FSH prevents the increase in belly fat. The second aim of the study is to determine whether decreasing the high FSH level in postmenopausal women causes a decrease in belly fat and changes other factors that are typically thought to be related to estrogen rather than FSH. Because estrogen and FSH levels fluctuate in premenopausal and early postmenopausal women, the investigators will use an approach that controls estrogen and FSH levels to address the aims. The investigators will use a drug that is typically used to treat endometriosis or uterine fibroids to reduce estrogen and FSH levels and an estrogen patch to increase estrogen in some women. The study will generate new knowledge on how menopause affects fat gain and disease risk.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
57
GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention)
Estrogen patches will be worn by those randomized to the Estradiol arms in both premenopausal and postmenopausal groups. Patches will be applied weekly and will be worn for the for entirety of the intervention (12 or 24 weeks).
Placebo patches will be worn by those randomized to the placebo arms in both premenopausal and postmenopausal groups. Patches will be applied weekly and will be worn for the for entirety of the intervention (12 or 24 weeks).
University of Colorado - Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGChange in the Microdialysis Cortisone Challenge (MCC) Index
The MCC Index is an in vivo measurement of local cortisol production in abdominal adipose tissue. A higher MCC Index is an indicator of more local cortisol production.
Time frame: Baseline, week 12
Change in the Oral Cortisone Challenge (OCC) Area Under the Curve (AUC)
The OCC AUC is a systemic measurement of peripheral glucocorticoid metabolism. A higher OCC AUC is an indicator of more production of cortisol.
Time frame: Baseline, week 12
Change in lumbar spine Bone Mineral Density (BMD)
Lumbar spine BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.
Time frame: Baseline, week 24
Change in resting energy expenditure (REE)
REE is an index of metabolic rate at rest, measured by indirect calorimetry. A higher REE is an indicator of greater energy expenditure at rest.
Time frame: Baseline, week 12, week 24
Change in visceral fat area (VFA)
VFA of the abdominal visceral region is measured by computed tomography. VFA is an indicator of the amount of fat stored in this region.
Time frame: Baseline, week 24
Change in flow-mediated dilation (FMD)
FMD of the brachial artery as an index of vascular function. A higher number is a general indicator of better vascular function.
Time frame: Baseline, week 12, week 24
Change in proximal femur Bone Mineral Density (BMD)
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Postmenopausal women randomized to the placebo injection arm will receive two placebo drug injections of normal saline (24-week intervention)
Proximal femur BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.
Time frame: Baseline, week 24