Effects of Estrogen Deficiency on Energy Expenditure

Study Overview
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Brief Summary
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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
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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.

Official Title
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Ovarian Function and Facultative Thermogenesis

Conditions
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Obesity

Intervention / Treatment
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* Drug: Estrogen suppression


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |