Testosterone Effects on Men With the Metabolic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00382057
Recruitment Status : Withdrawn
First Posted : September 28, 2006
Last Update Posted : December 5, 2008
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Brief Summary:
The metabolic syndrome is a medical condition defined by high levels of cholesterol in the blood, high blood pressure, central obesity (gain in fat around the region of the stomach), and insulin resistance (body responds less well to insulin). This state of impaired insulin resistance can lead to type 2 diabetes mellitus, which is one of the most common metabolic disorders in the U.S. Numerous studies have shown an inverse relationship between insulin resistance and testosterone levels in men, however, causality has not been established. This protocol investigates the role of testosterone in modulating insulin sensitivity in insulin resistant states such as the metabolic syndrome. The hypothesis is that testosterone administration will improve insulin sensitivity.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Drug: Testosterone Drug: Anastrozole Drug: Goserelin Phase 2

Detailed Description:

This protocol will address the impact of three months of testosterone (T) therapy on all components of the metabolic syndrome and the mechanism underlying changes in insulin sensitivity by analyzing changes in body composition, and detailed studies of fat metabolism and skeletal muscle. In addition, this protocol will address the role of estradiol (E2) in mediating the effect of testosterone on insulin sensitivity.

Seventy-two subjects will undergo a screening visit to assess eligibility after which a baseline evaluation will be performed. The baseline metabolic assessment will consist of an intravenous glucose tolerance test (IVGTT) to measure insulin sensitivity, MRI and DEXA scan to assess muscle and body fat distribution, VO2 max test and resting metabolic rate, and a muscle biopsy to look at how the muscle is affected by insulin and testosterone.

Subjects will then be randomized to one of three 12-week treatment arms, 1) Group 1 (Placebo); 2) Group 2 (Depot GnRH agonist (Zoladex) + T + placebo); or 3) Group 3 (Zoladex + T + aromatase inhibitor (anastrozole)). The rationale for this study design is as follows. Under normal physiological conditions, administration of T leads to a concomitant increase in E2 levels due to endogenous conversion by the aromatase enzyme system. Therefore, in order to dissect the relative roles of T and E2 on insulin sensitivity, one group of subjects will receive T in conjunction with the aromatase inhibitor, anastrozole.

At 13 weeks, the entire baseline evaluation including IVGTT, resting metabolic rate and VO2 max, body composition assessment by DEXA and MRI, and muscle biopsy will be repeated. Subjects will return for a follow up visit four weeks later to measure CBC, T and PSA levels, to ensure levels are within the normal range.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Effect of Increasing Testosterone Levels on Insulin Sensitivity in Men With the Metabolic Syndrome
Study Start Date : May 2006
Estimated Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. insulin sensitivity
  2. muscle and body fat distribution
  3. VO2 max
  4. resting metabolic rate
  5. muscle biopsy analysis

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age 50-75 yr
  2. Diagnosis of the metabolic syndrome defined by the American Heart Association/National Heart, Lung, and Blood Institute guidelines as the presence of three or more of the following:

    • Waist circumference > 102 cm
    • Serum triglycerides > 150 mg/dL
    • HDL cholesterol < 40 mg/dL
    • Blood pressure > 130 mm Hg systolic or 85 mm Hg diastolic, or treatment with anti-hypertensives
    • Fasting serum glucose > 100 mg/dL
  3. Plasma total testosterone level less than 300 ng/dL (1 SD below the mean for young healthy men)
  4. Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)
  5. Normal TSH, prolactin and prostate specific antigen (PSA) levels (<2.5 ng/mL)

Exclusion Criteria:

  1. New diagnosis of type 2 diabetes as defined by the ADA criteria: fasting glucose greater than 126 mg/dL or random blood glucose greater than 200 mg/dL on two occasions, or on oral hypoglycemic agents
  2. History of testicular disorders (i.e. cryptorchidism)
  3. History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
  4. History of prostate cancer
  5. History of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence)
  6. Symptoms of urinary outflow obstruction (i.e. benign prostatic hypertrophy)
  7. Illicit drug use or heavy alcohol use (>4 drinks/day)
  8. Allergic disorders
  9. Current medications (must exclude individuals taking the following medications: Testosterone, Cimetidine, Spironolactone, Ketoconazole, Finasteride, DHEA, Androstenedione, Oral steroids, GnRH analogs)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00382057

Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Director: William F Crowley, MD Massachusetts General Hospital
Principal Investigator: Frances J Hayes, MD Massachusetts General Hospital Identifier: NCT00382057     History of Changes
Other Study ID Numbers: 5 K23 DK02858-1526
5 K23 DK02858-02 6/15/05
First Posted: September 28, 2006    Key Record Dates
Last Update Posted: December 5, 2008
Last Verified: November 2008

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Insulin resistance
Insulin sensitivity
Metabolic disorders

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists