This study aims to determine whether testosterone replacement improves insulin sensitivity in non-obese men with low testosterone and the metabolic syndrome. The metabolic syndrome includes three of the following five conditions, 1) an elevated blood pressure (greater than 130/85), 2) a triglyceride level greater than 150 mg/dl, 3) an HDL-cholesterol less than 40 mg/dl, 4) glucose levels greater than 100 mg/dl, and 5) a waist measurement greater than 40 inches.

In this proposal, we will examine the relationship between hypogonadism and insulin sensitivity. The strongest relationship between hypogonadism and insulin resistance appears to reside in men with the metabolic syndrome who have a normal BMI. The causal relationship between these two conditions is unknown. Therefore, we propose to determine if testosterone replacement in hypogonadal non-obese men with metabolic syndrome will improve insulin sensitivity. Data obtained from this preliminary investigation, will hopefully result in a hypothesis that can be tested in a larger, more rigorous trial in the future.

Inclusion Criteria: (subjects must meet both criteria)

• Metabolic syndrome (have 3 out of the following 4 criteria):

  1. BP > 130/85 or on antihypertensive therapy
  2. Fasting glucose > 100 mg/dl
  3. Fasting TG > 150 mg/dl or on a triglyceride lowering agent (fenofibrate, gemfibrozil, niacin in doses of >= 500 mg/day, or fish oils in doses of >=2000mg DHA+EPA)
  4. Fasting HDL-C < 40 mg/dl Note that the waist circumference will not be used as one of the criteria for the metabolic syndrome for this study because we are studying non-obese subjects.

• Total Testosterone less than 300 ng/dl

Exclusion Criteria:

• Women.

• Men less than 20 years of age.

• BMI > or = to 30 kg/M2.

• Use of testosterone preparations within 1 year of the screening visit

• Use of hypoglycemic medications within the previous 3 months.

• Fasting blood glucose > 126 mg/dl.

• The following men will be excluded because of the potential safety issues in the placebo treated group:

  1. Creatinine greater than 1.4 mg/dl
  2. Triglyceride levels greater than 500 mg/dl
  3. HDL-C levels less than 20 mg/dl
  4. Blood pressure greater than 160/90

• The following men will be excluded because of the potential side effects of testosterone therapy:

  1. Men greater than 65 years of age
  2. International prostate symptom score >19
  3. PSA greater than 2.5
  4. History of benign prostatic hypertrophy
  5. History of prostate cancer
  6. Abnormal digital rectal exam
  7. Hg greater than 16 mg/dl or Hct greater than 48%
  8. peripheral edema