Testosterone Replacement in Older Men and Atherosclerosis Progression

• Status: Completed
• Trial end date: 2012-05-12
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Boston University; Brigham and Women's Hospital
• Collaborator: Solvay Pharmaceuticals
• Treatments: Methyltestosterone; Testosterone; Testosterone 17 beta-cypionate; Testosterone enanthate; Testosterone undecanoate

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.