Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause

Understanding the Roles of Estradiol and Follicle-stimulating Hormone in Adipocyte Remodeling Following Surgical and Pharmacology-induced Menopause (RESUME-2 Study)

The overarching aims of this study are to:

1. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing surgical menopause (↓E2, ↑FSH).
2. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing gonadal suppression (↓E2, ↓FSH).

This is a cross-sectional study where two groups of premenopausal women (ages 18-50 y) will be enrolled in a parallel arm study:

• Arm 1 (Surgical Menopause): up to 6 women undergoing laparoscopic, elective bilateral oophorectomy [Site: Pennington Biomedical Research Center].
• Arm 2 (Pharmacology-Induced Menopause): up to 6 women undergoing gonadal suppression via leuprolide acetate (Lupron [AbbVie Inc.]) [Site: UC-Denver].

We will compare each arm of women to non-oophorectomized, premenopausal women (controls) with normal menstrual cycles (Apple&Pear study; NCT01748994; PI: Ravussin) selectively matched (1:2) for age and BMI. The Apple&Pear study uses the same in vivo adipogenesis labeling protocol, with similar age and BMI criteria, as the proposed study.

INCLUSION CRITERIA:

• Healthy female
• Ages 18-50 y
• Planning to have either a laparoscopic bilateral oophorectomy or a laparoscopic unilateral oophorectomy (which would result in no remaining ovaries)
• Are willing to drink heavy water (2H2O) over an 8-week period
• Medically cleared for participation in the study by OB/GYN and Medical Investigator
• Are willing to have blood and fat tissue stored for future use

EXCLUSION CRITERIA:

• Meet either of the following criteria:

• Have all 3 of the major menopause-related symptoms [hot flashes, mood swings, insomnia (trouble sleeping)]

• Have 2 of the major menopause-related symptom combinations [hot flashes and mood swings, or hot flashes and insomnia (trouble sleeping)]

• Unstable weight in the last 3 months [gain or loss >7 lb (or 3.2 kg)]

• History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL

• Chronic use of systemic glucocorticoids, antipsychotic/antidepressant medications, thiazolidinediones and other medications that cause clinically significant weight gain, weight loss or are known to make changes in fat cell number/size *

• Previous bariatric surgery (or other surgeries) for obesity or weight loss (< 3 years ago)

• Use of over the counter or prescription weight loss products

• History of metabolic diseases (other than diabetes)

• History of neurological disease

• History of cardiovascular disease (or other chronic diseases)

• Pregnant, planning to become pregnant, or breastfeeding

• Use of hormone replacement therapy

• Unwilling to discontinue any form or hormonal therapy (e.g., contraceptives including birth control pills, vaginal ring, injections, implant, or skin patch; hormonal supplements, etc.) upon enrollment (after the Screening Visit).

  • Inconsistent use of medications listed above will be evaluated and left up to the discretion of the Medical Investigator to evaluate safety.