Regulation of Cortisol Metabolism and Fat Patterning

The purpose of this study is to determine if estrogen or testosterone can affect cortisol levels and where fat builds up in our bodies.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Menopausal Syndrome
• Intervention / Treatment: Drug: Placebo injection; Drug: Depo Lupron/Aromatase inhibitor; Drug: Depo Lupron/placebo; Drug: placebo; Drug: Estrogen cream

Detailed Description

Subjects will be studied 3 or 4 times on the inpatient unit of the Oregon Clinical and Translational Research Center. During each visit, testing will include measuring the amount of whole body fat and fat in the stomach area, muscle, and liver; levels of cortisol in the blood, urine, and fat tissue (taken from a biopsy); how well insulin works (insulin sensitivity).

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 62 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 40 postmenopausal women (age 40-62) and 30 men (age 18-45) will be recruited if they are healthy, at their lifetime maximal weight, have been weight stable for at least six months prior to entry, have a BMI between 19 and 39.9 kg/m2, and be willing to commit to not making significant changes to their diet or daily activities while enrolled in the study.

Exclusion Criteria:

• Subjects will be excluded for potential confounders on body weight, cortisol production rates, sex steroid metabolism, or contraindications to strong magnetic fields:

  1. Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth
  2. Subjects who exercise > 30 minutes/day, 3 times a week
  3. Smokers
  4. Heavy alcohol drinkers (> 2 drinks/ day)
  5. Subjects with medical diagnosis including diabetes, heart disease, and cancer
  6. Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders)
  7. BMI 40 kg/m2, since obesity influences levels of sex steroids and sex hormone binding globulin; or body weight > 136 kg (300 lbs), since this is the weight limit for the DEXA and MR machines
  8. Presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips
  9. Endocrine diseases affecting body composition, such as untreated hypothyroidism or Cushing's syndrome, will be excluded by history and physical examination, or by laboratory evaluation if necessary.
• Women with a contraindication to estrogen use will also be excluded, including: an estrogen dependent malignancy, active thrombophlebitis, history of deep venous thrombosis, hypertriglyceridemia, untreated hypertension, cardiovascular disease, migraine headaches, or current tobacco use.
• Women with frequent hot flashes or disrupted sleep will also be excluded since they will be unlikely to tolerate randomization to placebo and continued symptoms and altered sleep cycles will independently affect cortisol secretion patterns.
• All volunteers will have had a normal mammogram within the previous 12 months.
• Any subject with previously unevaluated postmenopausal bleeding will not be included and, instead, will be referred to a physician for evaluation.
• Women who underwent surgical menopause (bilateral ovariectomy) must be at least one year out from their surgery before considered eligible so as to allow weight stabilization after the procedure.
• Men will have had a prostate exam by their primary health provider within the previous year or by the PI at the time of screening for this study.
• Any subjects taking a blood thinning medication or with an abnormal exam will not be included and, instead, will be referred to a physician for evaluation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Men on placebo injections for 4 months	Drug: Placebo injection; Normal saline injection IM monthly for 4 months; Other Names: Normal Saline
Active Comparator: 2; Men who receive Depo Lupron for 4 months, then are replaced with testosterone and aromatase inhibitor for 4 months.	Drug: Depo Lupron/Aromatase inhibitor; Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and aromatase inhibitor months 4-8.; Other Names: Anastrozole; Arimidex; Depo-Lupron; Testim 1% gel
Active Comparator: 3; Men who receive Depo Lupron for 4 months, then are replaced with testosterone and placebo for 4 months.	Drug: Depo Lupron/placebo; Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and placebo months 4-8.; Other Names: Placebo capsules; Depo-Lupron; Testim 1% gel
Placebo Comparator: 4; Women on placebo cream	Drug: placebo; Placebo Cream 1ml applied twice daily for four months; Other Names: Placebo cream
Active Comparator: 5; Women on estrogen cream	Drug: Estrogen cream; Estrogen cream 1 ml twice daily, dose titrated to maintain estradiol level between 60 and 280 pg/ml.; Other Names: Estradiol cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To measure 24-hour CPR, free cortisol, and cortisol binding globulin levels in plasma; HSD 1 activity, glucocorticoid receptor binding, and cortisol levels in adipocytes; and urinary excretion of cortisol, cortisone and their metabolites.	Before and after hormone replacement therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
To measure intramyocellular fat and intrahepatic fat by MRS, visceral and subcutaneous abdominal fat by CT scan, body composition (fat mass, lean mass, and bone mass) by DXA, and insulin sensitivity.	Before and after hormone replacement therapy

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Jonathan Q. Purnell, M.D., OHSU - Center for the Study of Weight Regulation

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: June 6, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimate): June 10, 2008

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Obesity; Cortisol; Menopausal Syndrome
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgens; Anabolic Agents; Leuprolide; Estradiol; Testosterone; Anastrozole; Estrogens; Aromatase Inhibitors; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: eIRB #937; OCTRI #862 (Other Identifier: Oregon Health and Sciences University)