Females, Aging, Metabolism, and Exercise (FAME)

Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women

This study is designed to determine whether a reduction in hormones (such as occurs during menopause) causes a decrease in calories burned during physical activity. This study will also determine whether a reduction in hormones decreases calories burned while sleeping, resting, and eating and whether an exercise intervention can prevent this.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: GnRH agonist; Behavioral: Supervised cardiovascular exercise

Detailed Description

Participants will be women who are nearing menopause based on age (42-52 y) but have normal menstrual cycles. Participants will be randomized to receive monthly injections of placebo or a study drug that reduces sex hormones (GnRH agonist) for 24 weeks. Women who receive GnRH agonist will be further randomized to no exercise or a supervised exercise program. Thus, the 3 treatment groups are: placebo, GnRH agonist, GnRH agonist+exercise. The investigators will measure changes in calories burned during physical activity, sleep, rest, and after a meal after 3 and 6 months of hormone suppression using doubly-labeled water and room calorimetry. Other measures include food intake estimated from food records; body composition measured by dual-energy x-ray absorptiometry (DXA); glucose and insulin responses to an oral glucose tolerance test; and markers of inflammation in the blood.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy women aged 40 to 60 years
2. Are still experiencing regular menstrual cycles.
3. They must be willing to be randomized to placebo or GnRHAG therapy for 24 weeks
4. Be physically able to be randomized to participate in a programmed exercise training program.

The investigators will consent up to 132 subjects with the aim of enrolling 22 in each of the 3 groups (placebo, GnRHAG, or GnRHAG+Exercise).

Exclusion Criteria:

• irregular menstrual cycles defined as 2 or more missed cycles in the previous year
• serum FSH >25 mIU/mL measured during the first 5 days of the menstrual cycle
• on hormonal contraceptive or menopausal therapy
• positive pregnancy test
• intention to become pregnant or start hormonal contraceptive therapy during the period of study
• lactation
• known hypersensitivity to GnRH or leuprolide acetate
• score >16 on the CESD((Center for Epidemiologic Studies Depression Scale )
• severe osteopenia or osteoporosis (i.e., proximal femur or lumbar spine t scores < -2.0)
• abnormal vaginal bleeding
• thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement
• uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the PCP with initiation or adjustment of anti-hypertensive medications
• cardiovascular disease; subjective or objective indicators of ischemic heart disease (e.g., angina, ST segment depression) or serious arrhythmias at rest or during the graded exercise test (GXT) without follow-up evaluation; follow-up evaluation must include diagnostic testing (e.g., thallium stress test) with interpretation by a cardiologist
• orthopedic or other problems that would interfere with participation in the exercise program
• exercising at least 30 minutes per day at a moderate to vigorous intensity most days of the week (defined as >4 d/wk) over the past 6 months
• BMI <40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Monthly placebo injections for 6 months	Drug: Placebo; Placebo
Active Comparator: GnRH agonist; Monthly GnRH agonist injections for 6 months	Drug: GnRH agonist; Drug: leuprolide acetate Other Names: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 6 months; Other Names: Leuprolide Acetate 3.75mg
Active Comparator: GnRH agonist + exercise; Monthly GnRH agonist injections for 6 months plus supervised cardiovascular exercise intervention	Drug: GnRH agonist; Drug: leuprolide acetate Other Names: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 6 months; Other Names: Leuprolide Acetate 3.75mg; Behavioral: Supervised cardiovascular exercise; Supervised exercise, 4 days per week for 45 to 60 minutes per session for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Physical Activity Energy Expenditure (PAEE)	PAEE will be calculated as: TEE - REE - TEF, where TEE is total energy expenditure (measured by doubly-labeled water), REE is resting energy expenditure (measured by indirect calorimetry), and TEF is the thermic effect of feeding (estimated using a constant).	Change from baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Fat Mass	Total Fat mass as measured by DXA	Change over 6 months
Total Fat Free Mass	Total Fat Free Mass as measured by DXA	Change over 6 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

General Publications

• Gavin KM, Melanson EL, Hildreth KL, Gibbons E, Bessesen DH, Kohrt WM. A Randomized Controlled Trial of Ovarian Suppression in Premenopausal Women: No Change in Free-Living Energy Expenditure. Obesity (Silver Spring). 2020 Nov;28(11):2125-2133. doi: 10.1002/oby.22978.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 22, 2012
• First Posted (Estimate): October 23, 2012

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: menopause; obesity; hormone therapy; metabolic syndrome; women's health; disease /disorder proneness /risk; insulin sensitivity /resistance
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: 12-1157; P50HD073063 (U.S. NIH Grant/Contract)