Obesity
Conditions
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.
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.
Interventions
DRUGEstrogen suppression
Estrogen production will be suppressed for 3 months by administering a drug, lupron, that suppresses ovarian function
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cold Induced Thermogenesis | Baseline and after 3 months of suppression | The increase in energy expenditure above resting during cold exposure |
| Fat Mass | Baseline and after 3 months of suppression | Amount of body fat (in kg) |
| Fat Free Mass | Baseline and after 3 mo of suppression | Fat free mass measured by DXA |
| Resting Energy Expenditure | after 3 months of suppression | Energy expenditure measured in the resting state |
Countries
United States
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
Participants by arm
| Arm | Count |
|---|---|
| Estrogen Suppression 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). | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Estrogen Suppression |
|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 6 |
| Body mass index | 24.3 kg/m^2 STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| fat free mass (from DXA) | 40.3 kg STANDARD_DEVIATION 8.4 |
| Fat mass (measured with DXA) | 24.2 kg STANDARD_DEVIATION 8.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight | 64.8 kg STANDARD_DEVIATION 16.3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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).
Time frame: Baseline and after 3 months of suppression
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Estrogen Suppression | Brown Adipose Tissue Activity | Baseline | 3.9 Standard uptake value (SUV) | Standard Deviation 1.8 |
| Estrogen Suppression | Brown Adipose Tissue Activity | 3 mo | 4.0 Standard uptake value (SUV) | Standard Deviation 2 |
p-value: 0.84t-test, 2 sided
Secondary
Cold Induced Thermogenesis
The increase in energy expenditure above resting during cold exposure
Time frame: Baseline and after 3 months of suppression
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Estrogen Suppression | Cold Induced Thermogenesis | Baseline | 350 kcal | Standard Deviation 228 |
| Estrogen Suppression | Cold Induced Thermogenesis | 3 mo | 301 kcal | Standard Deviation 139 |
Comparison: 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 deviationsp-value: 0.66t-test, 2 sided
Secondary
Fat Free Mass
Fat free mass measured by DXA
Time frame: Baseline and after 3 mo of suppression
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Estrogen Suppression | Fat Free Mass | Baseline | 40.3 kg | Standard Deviation 8.4 |
| Estrogen Suppression | Fat Free Mass | 3 mo | 40.4 kg | Standard Deviation 8.3 |
Comparison: 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 deviationsp-value: 0.98t-test, 2 sided
Secondary
Fat Mass
Amount of body fat (in kg)
Time frame: Baseline and after 3 months of suppression
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Estrogen Suppression | Fat Mass | Baseline | 24.2 kg | Standard Deviation 8.9 |
| Estrogen Suppression | Fat Mass | 3 mo | 24.1 kg | Standard Deviation 4.5 |
p-value: 0.92t-test, 2 sided
Secondary
Resting Energy Expenditure
Energy expenditure measured in the resting state
Time frame: after 3 months of suppression
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Estrogen Suppression | Resting Energy Expenditure | Baseline | 1382 kcal | Standard Deviation 218 |
| Estrogen Suppression | Resting Energy Expenditure | 3 mo | 1340 kcal | Standard Deviation 209 |
Comparison: 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 deviationsp-value: 0.66t-test, 2 sided