Effects of Estrogen Deficiency on Energy Expenditure

Ovarian Function and Facultative Thermogenesis

Menopause is associated with weight gain, but the reasons why are not clear. In this study, the investigators will determine if reducing estrogen levels causes a decrease in the ability of the body to produce heat. If so, this would suggest this is one way that menopause may cause weight gain.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Estrogen suppression

Detailed Description

The purpose of this pilot study is to investigate the role of the female sex hormone estrogen, on metabolism, thermoregulation and energy expenditure. Weight and fat gain increase after the menopause, but reasons for this are not clear. Loss of estrogen may cause changes in how women regulate metabolism and thermoregulation, possibly leading to weight gain. Specifically, this study will determine how loss of estrogen affects facultative thermogenesis. Loosely defined, facultative thermogenesis represents heat production that is turned on when needed. For example, when body core temperature falls below a certain threshold, a shivering response is invoked in skeletal muscle to increase heat production and, thus, energy expenditure. However, exposure over several hours to mild cold temperatures that do not trigger shivering (16-20⁰ C) also induces an increase in energy expenditure (cold-induced non-shivering thermogenesis). Although several different tissues may contribute to this response, the recent identification of functional brown adipose tissue (BAT) in humans has promoted an interest in how BAT is activated in humans and its potential role in regulating energy balance and body weight. The investigators will measure BAT activity using PET/CT scans pre and post three months of estrogen suppression.

• Study Type: Interventional
• Enrollment (Actual): 6
• 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: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Body mass index < 30 kg/m2
• Normal menstrual cycles
• Premenopausal

Exclusion Criteria:

• irregular menstrual cycles defined as 2 or more missed cycles in the previous year
• on hormonal contraceptive or menopausal therapy
• positive pregnancy test
• intention to become pregnant or start hormonal contraceptive therapy during the period of study
• lactation
• severe osteopenia or osteoporosis (i.e., proximal femur or lumbar spine t scores < -2.0)
• abnormal vaginal bleeding
• thyroid dysfunction
• uncontrolled hypertension
• exercising at least 30 minutes per day at a moderate to vigorous intensity >1 d/wk) over the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estrogen suppression; Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones	Drug: Estrogen suppression; Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function; Other Names: Lupron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brown Adipose Tissue Activity	Brown adipose tissue activity will be measured using Positron Emission Tomography/computer tomography (PET/CT) before and after 3 months of estrogen suppression. Activity is quantified as the standard uptake value (SUV), It is a mathematically derived ratio that is a semiquantitative measure of the tracer uptake in a region of interest that normalizes the lesion activity to the injected activity and a measure of the volume of distribution (usually total body weight or lean body mass).	Baseline and after 3 months of suppression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cold Induced Thermogenesis	The increase in energy expenditure above resting during cold exposure	Baseline and after 3 months of suppression
Fat Mass	Amount of body fat (in kg)	Baseline and after 3 months of suppression
Fat Free Mass	Fat free mass measured by DXA	Baseline and after 3 mo of suppression
Resting Energy Expenditure	Energy expenditure measured in the resting state	after 3 months of suppression

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Edward Melanson, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: April 30, 2013
• First Submitted That Met QC Criteria: April 30, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: 13-0149; P50HD073063 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO