Testosterone Replacement in Older Men and Atherosclerosis Progression
Condition: Hypogonadism; Atherosclerosis
MeSH terms: Atherosclerosis; Hypogonadism
Intervention: Testosterone Gel (Androgel); Placebo
Intervention description: 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years; Placebo-matching testosterone gel daily for 3 years
Intervention MeSH terms: Testosterone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 308.0
Sex: Male
Minimum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Testosterone Replacement; Heart Disease; Vascular Disease; Risk Factors for Cardiovascular Disease; Cholesterol; Obesity; Blood pressure; Quality of Life

Summary:

      As men grow older, their testosterone levels decrease with age. One-third of men, 70 years of
      age or older, have low testosterone levels. It is known that short-term testosterone
      replacement is safe, and can increase muscle strength and physical function, but the risks of
      long-term testosterone replacement in older men with low testosterone levels are incompletely
      understood.

      Atherosclerosis is characterized by thickening of the artery walls, and the narrowing of the
      blood vessels as cholesterol is deposited in the lining of the arteries. It is the major
      cause of cardiovascular disease including ischemic heart disease (heart attacks) and stroke.
      Although, historically, there has been a widespread perception that higher levels of
      testosterone might increase the risk of atherosclerosis, the evidence from research does not
      support this. In observational studies, higher testosterone levels have been correlated with
      more favorable cardiovascular risk factors, and supplementation with testosterone to bring
      older men into the normal range for healthy younger men appears to improve several
      cardiovascular risk factors, and may slow the progression of atherosclerosis.

      The primary purpose of this study is to look at the effects of testosterone replacement on
      the progression of atherosclerosis in older men. This study is also being done to find out
      whether replacement with testosterone in older men with low testosterone levels improves
      their health-related quality of life.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 60 years or greater

          -  Hypogonadism, Testosterone 100-400 ng/dl or Free Testosterone < 50 pg/ml

          -  Generally good health

          -  At least 8 years of primary school education

          -  Able to pass screening test for dementia

          -  Able to give informed consent

        Exclusion Criteria:

          -  Testosterone level < 100 ng/dl (these individuals will be referred for evaluation of
             severe hypogonadism)

          -  Use of testosterone or other androgens [dehydroepiandrosterone (DHEA),
             Androstenedione] in last year

          -  Use of growth hormone in the last year

          -  Current alcohol of drug dependence [Alcohol Use Disorders Identification Test (AUDIT)
             Score > 8]

          -  Diseases known to affect gonadal function

          -  Medications known to affect gonadal function eg. anticonvulsants, glucocorticoids such
             as prednisone

          -  Prostate cancer, breast cancer

          -  Any cancer that may limit life expectancy to less than 5 years

          -  Limiting neuromuscular, joint or bone disease

          -  History of stroke with residual neurologic deficit

          -  Neurologic condition that would impair cognitive function including:

        epilepsy, multiple sclerosis, human immunodeficiency virus (HIV), Parkinson's disease,
        stroke

          -  Psychiatric disorder in the last year meeting Diagnostic and Statistical Manual of
             Mental Disorders, 4th edition (DSMIV) Axis 1 criteria

          -  Use of psychotropic medicine for at least 6 months

          -  Dementia as assessed by (Telephone Interview for Cognitive Status modified score less
             than 31)

          -  Severe symptoms of benign prostatic hyperplasia (BPH) (American Urological Association
             symptom index score greater than 21)

          -  Prostate nodule or induration of digital rectal exam (DRE)

          -  Prostate specific antigen (PSA) greater than 4 unless participant has had a negative
             transrectal biopsy within last 3 months

          -  Limiting heart disease in including New York (NY) Class III or IV - congestive heart
             failure, unstable angina, or myocardial infarction (MI) in last 3 months

          -  Liver function tests [aspartate aminotransferase (AST) and alanine
             aminotransferase(ALT)] greater than 3 times the upper limit of the reference range

          -  Serum creatinine (Cr) greater than 2.5 mg/dl

          -  Hematocrit greater than 48%

          -  Hemoglobin (Hb)A1c greater than 9.0%

          -  Untreated thyroid disease

          -  Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic
             blood pressure greater than 100 mmHg)

          -  Body mass index (BMI greater than 35 kg/m2)

          -  Untreated severe obstructive sleep apnea

          -  Development of electrocardiogram (EKG) changes consistent with myocardial ischemia or
             changes in blood pressure during cardiopulmonary exercise testing will be excluded
             from testing of muscle strength and physical function.