Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels

Abstract

IMPORTANCE Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.OBJECTIVE To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS Testosterone's Effects on Atherosclerosis Progression inAging Men (TEAAM) 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 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012.INTERVENTIONS 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. MAIN OUTCOMES AND MEASURESCoprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life.RESULTS 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% CI, −0.003 to 0.003, P = .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 = .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 testosterone group.CONCLUSIONS AND RELEVANCE Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs 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 nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men.

Low Testosterone: A Risk Marker Rather Than a Risk Factor for Type 2 Diabetes

“…Results from a recently published placebo-controlled, randomized trial on testosterone treatment including older, community-dwelling men with testosterone levels in the lower range indicated that there are no beneficial effects of testosterone administration in healthy men on the risk of atherosclerosis in line with our interpretation of the current study (28).…”

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

“…The lack of definite response in some areas does not diminish the clearly proven efficacy in others, including areas of considerable importance to men. Some studies have reported no sexual benefits with T therapy, such as the study by Basaria et al 84 Notably, however, their study population was recruited without a requirement for baseline symptoms and included men with normal T concentrations. There is no reason to expect men without symptoms to have symptomatic improvement with treatment, particularly if they do not have true TD.…”

Meta-analysis of Results of Testosterone Therapy on Sexual Function Based on International Index of Erectile Function Scores

“…Out of 284 retrieved articles, 14 were included in the study [24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, one study [24] not adequately reporting p values or mean differences was used only when standardized effect size calculations (standardized difference in means [SDM]) were performed.…”