Effects of Estrogen Deficiency on Energy Expenditure

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01846728
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Estrogen suppression	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Ovarian Function and Facultative Thermogenesis
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Brown Adipose Tissue Activity [Baseline and after 3 months of suppression]

   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).

Secondary Outcome Measures

1. Cold Induced Thermogenesis [Baseline and after 3 months of suppression]

   The increase in energy expenditure above resting during cold exposure

2. Fat Mass [Baseline and after 3 months of suppression]

   Amount of body fat (in kg)

3. Fat Free Mass [Baseline and after 3 mo of suppression]

   Fat free mass measured by DXA

4. Resting Energy Expenditure [after 3 months of suppression]

   Energy expenditure measured in the resting state

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Edward Melanson, PhD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01846728
• Other Study ID Numbers: 13-0149; P50HD073063
• First Posted: May 3, 2013
• Last Update Posted: Nov 18, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Estrogens

Study Results

Participant Flow

Recruitment Details	Participants were recruited through advertisements posted on the Anschutz Medical Campus and distributed through the campus email system. 12 women consented to participate in the study (consent was obtained prior to screening and orientation). After the screening and orientation process, 6 elected to continue, and 6 elected not to continue

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Participants underwent 3 mo of ovarian hormone suppression using the GnRHAG leuprolide acetate (Lupron; TAP Pharmaceutical Products, Inc; Lake Forest, IL) delivered by monthly intramuscular injection (3.75 mg).
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Participants underwent 3 mo of ovarian hormone suppression using the GnRHAG leuprolide acetate (Lupron; TAP Pharmaceutical Products, Inc; Lake Forest, IL) delivered by monthly intramuscular injection (3.75 mg).
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31 (6)
Sex: Female, Male (Count of Participants)
Female	6 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 16.7%
White	4 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.3 (4.5)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	64.8 (16.3)
Fat mass (measured with DXA) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	24.2 (8.9)
fat free mass (from DXA) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	40.3 (8.4)

Outcome Measures

1. Primary Outcome

Title	Brown Adipose Tissue Activity
Description	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).
Time Frame	Baseline and after 3 months of suppression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Measure Participants	6
Baseline	3.9 (1.8)
3 mo	4.0 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Estrogen Suppression
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Because this was a pilot study, the study was not powered to detect differences over time. the study was performed to generate preliminary data on means and standard deviations
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Cold Induced Thermogenesis
Description	The increase in energy expenditure above resting during cold exposure
Time Frame	Baseline and after 3 months of suppression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Measure Participants	6
Baseline	350 (228)
3 mo	301 (139)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Estrogen Suppression
	Comments	Because this was a pilot study, the study was not powered to detect differences over time. the study was performed to generate preliminary data on means and standard deviations
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Fat Mass
Description	Amount of body fat (in kg)
Time Frame	Baseline and after 3 months of suppression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Measure Participants	6
Baseline	24.2 (8.9)
3 mo	24.1 (4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Estrogen Suppression
	Comments
	Type of Statistical Test	Other
	Comments	Because this was a pilot study, the study was not powered to detect differences over time. the study was performed to generate preliminary data on means and standard deviations
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Fat Free Mass
Description	Fat free mass measured by DXA
Time Frame	Baseline and after 3 mo of suppression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Measure Participants	6
Baseline	40.3 (8.4)
3 mo	40.4 (8.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Estrogen Suppression
	Comments	Because this was a pilot study, the study was not powered to detect differences over time. the study was performed to generate preliminary data on means and standard deviations
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Resting Energy Expenditure
Description	Energy expenditure measured in the resting state
Time Frame	after 3 months of suppression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Measure Participants	6
Baseline	1382 (218)
3 mo	1340 (209)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Estrogen Suppression
	Comments	Because this was a pilot study, the study was not powered to detect differences over time. the study was performed to generate preliminary data on means and standard deviations
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	Estrogen Suppression
Arm/Group Description	Estrogen production will be suppressed using Lupron, a drug that blocks normal production of ovarian hormones Estrogen suppression: Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
All Cause Mortality
	Estrogen Suppression
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Estrogen Suppression
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Estrogen Suppression
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
General disorders
Headaches	1/6 (16.7%)	1
Reproductive system and breast disorders
Vaginal Bleeding	1/6 (16.7%)	1

Limitations/Caveats

This was a pilot study to generate preliminary data for an NIH grant application. there was insufficient power to detect significant differences.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.