Intervention: Testosterone
Trial phase: Phase 4
ATC code: G03BA03 | G03EA02
SMILES: [H][C@@]12CCC3=CC(=O)CC[C@]3(C)[C@@]1([H])CC[C@]1(C)[C@@H](O)CC[C@@]21[H]
Sex: Male
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 155
Group description: Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.)
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.