Phase 4 N=308 Randomized Double-blind Treatment

Testosterone Replacement in Older Men and Atherosclerosis Progression

Hypogonadism · Atherosclerosis

Bottom Line

View on ClinicalTrials.gov: NCT00287586 ↗

Enrolled (actual)

308

Serious AEs

16.0%

Results posted

Jun 2017

Primary outcome: Primary: Change From Baseline in Common Carotid Artery Intima-Media Thickness (IMT) — 0.877; 0.879; 0.036; 0.033 mm

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Testosterone Gel (Androgel) (Drug); Placebo (Drug)
Age: Adult, Older Adult · 60+ yrs
Sex: Male
Sponsor: Brigham and Women's Hospital
Primary completion: Feb 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Common Carotid Artery Intima-Media Thickness (IMT)	0.877; 0.879; 0.036; 0.033	—
PRIMARY Change From Baseline in Coronary Artery Calcium Score	451.78; 508.31; 103.61; 124.54	—
SECONDARY Change From Baseline in Lipid Profiles	187.15; 183.44; -14.88; -12.56; 47.11; 48.71	—
SECONDARY Changes in Biomarkers of Inflammation	—	—
SECONDARY Changes in Blood Pressure	—	—
SECONDARY Change From Baseline in Complex Figure (Immediate) and Complex Figure (Delayed)	20.95; 20.31; -1.25; -0.24; 20.28; 19.75	—
SECONDARY Change From Baseline in Paragraph Recall Test (Delayed)	13.69; 13.57; 2.15; 1.72	—
SECONDARY Change From Baseline in the Buschke Selective Reminding Test (Delayed)	8.00; 7.76; 0.47; 0.85	—
SECONDARY Change From Baseline in the Verbal Fluency Test	26.96; 27.02; 2.86; 1.77	—
SECONDARY Change From Baseline in the Category Fluency Test	18.07; 18.01; 2.25; 0.37	—
SECONDARY Change From Baseline in the Stroop Interference Test	55.64; 56.84; -1.07; 0.99	—
SECONDARY Change From Baseline in the Trail Making Test B	98.52; 97.57; 3.88; 11.26	—
SECONDARY Change From Baseline in Chest Press Strength and Leg Press Strength	516.99; 513.83; -12.73; -26.20; 2270.37; 2233.74	—
SECONDARY Change From Baseline in Unloaded Stair Climb Power and Loaded Stair Climb Power	536.33; 535.78; -8.17; -12.89; 581.24; 594.84	—
SECONDARY Change in Sexual Function as Assessed by the International Index of Erectile Function (IIEF)	18.33; 18.67; -0.15; -0.80; 7.37; 6.38	—
SECONDARY Change in Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36)	69.92; 71.21; -1.45; -0.46; 82.67; 83.17	—

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 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00287586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.