Regulation of Cortisol Metabolism and Fat Patterning

NCT00694733 | Unknown

• 2 other identifiers: eIRB #937OCTRI #862
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obesity; Menopausal Syndrome

Keywords

Obesity; Menopausal Syndrome; Cortisol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (5)

1

PLACEBO COMPARATOR

Men on placebo injections for 4 months

Drug: Placebo injection

2

ACTIVE COMPARATOR

Men who receive Depo Lupron for 4 months, then are replaced with testosterone and aromatase inhibitor for 4 months.

Drug: Depo Lupron/Aromatase inhibitor

3

ACTIVE COMPARATOR

Men who receive Depo Lupron for 4 months, then are replaced with testosterone and placebo for 4 months.

Drug: Depo Lupron/placebo

4

PLACEBO COMPARATOR

Women on placebo cream

Drug: placebo

5

ACTIVE COMPARATOR

Women on estrogen cream

Drug: Estrogen cream

Interventions

Placebo injection DRUG

Normal saline injection IM monthly for 4 months

Also known as: Normal Saline

1

Depo Lupron/Aromatase inhibitor DRUG

Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and aromatase inhibitor months 4-8.

Also known as: Depo-Lupron, Testim 1% gel, Anastrozole, Arimidex

2

Depo Lupron/placebo DRUG

Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and placebo months 4-8.

Also known as: Depo-Lupron, Testim 1% gel, Placebo capsules

3

placebo DRUG

Placebo Cream 1ml applied twice daily for four months

Also known as: Placebo cream

4

Estrogen cream DRUG

Estrogen cream 1 ml twice daily, dose titrated to maintain estradiol level between 60 and 280 pg/ml.

Also known as: Estradiol cream

5

Eligibility Criteria

• Age: 18 Years - 62 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Subjects will be excluded for potential confounders on body weight, cortisol production rates, sex steroid metabolism, or contraindications to strong magnetic fields:
• Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth
• Subjects who exercise \> 30 minutes/day, 3 times a week
• Smokers
• Heavy alcohol drinkers (\> 2 drinks/ day)
• Subjects with medical diagnosis including diabetes, heart disease, and cancer
• Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders)
• 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
• Presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips
• 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.

Sponsors & Collaborators

• Oregon Health and Science University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Saline Solution; Aromatase Inhibitors; Testosterone; Gels; Anastrozole

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Colloids; Complex Mixtures; Dosage Forms; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jonathan Q. Purnell, M.D.

  OHSU - Center for the Study of Weight Regulation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 6, 2008
• First Posted: June 10, 2008
• Study Start: May 1, 2005
• Primary Completion: March 1, 2024
• Study Completion: September 1, 2024
• Last Updated: December 16, 2022

Record last verified: 2022-12

Locations

US (1)