Effects of Testosterone on Atherosclerosis

Study Questions:

What are the effects of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels?


TEAAM (Testosterone’s Effects on Atherosclerosis Progression in Aging Men) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dl; free testosterone <50 pg/ml), recruited at three US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012. One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dl. Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life.


Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% confidence interval [CI], −0.003 to 0.003; p = 0.89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, −10.8 Agatston units/year; 95% CI, −45.7 to 24.2; p = 0.54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in the testosterone group. Hypertriglyceridemia was the only comorbidity whose remission rates at 1 year of follow-up (partial/complete, 80.6%; complete, 72.2%) correlated with percentage of excess weight loss (76.8%; p = 0.005).


The authors concluded that testosterone administration for 3 years versus placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium.


This trial reports that rates of subclinical atherosclerosis progression in community-dwelling older men with low or low-normal testosterone levels did not differ significantly between men assigned to the testosterone or placebo groups. Furthermore, testosterone administration was not associated with improved overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression and not cardiovascular events, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men such as those enrolled in this trial. Prospective studies with hard clinical endpoints are needed to ascertain cardiovascular safety of testosterone therapy.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Hypertriglyceridemia, Lipid Metabolism, Novel Agents, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Atherosclerosis, Carotid Intima-Media Thickness, Dyslipidemias, Hematocrit, Hypertriglyceridemia, Metabolic Syndrome X, Penile Erection, Primary Prevention, Prostate-Specific Antigen, Quality of Life, Testosterone

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