Are the Testosterone Trials the Final Word? A Primary Care Perspective

Kenneth W. Lin, MD, MPH


March 06, 2017

Editorial Collaboration

Medscape &

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Hi, everyone. I'm Dr Kenny Lin. I am a family physician at Georgetown University Medical Center in Washington, DC, and I blog at Common Sense Family Doctor.

One health news item from last year's presidential campaign was Donald Trump's normal total testosterone (T) level of 441,[1] even though Trump had not reported symptoms of hypogonadism, and in fact had vehemently denied erectile dysfunction during a televised primary debate. It is common for prominent politicians to undergo tests of questionable benefit. For example, then-48-year-old President Obama underwent a coronary calcium scan and CT colonography as part of a health maintenance exam early in his first term. But Trump's test reignited the controversy about whether primary care physicians ought to be routinely screening older men for low T and prescribing testosterone supplements for those with the diagnosis.

Spurred by direct-to-consumer advertisements warning of dire health consequences of "manopause" and urging men with low energy and diminished libido to "get back in the game," sales of prescription testosterone supplements are projected to top $4 billion this year.[2] Longitudinal studies show that serum T levels gradually decline with age, but it is unclear whether supplementing men with low T improves health. A recent systematic review[3] of more than 150 randomized controlled trials found no conclusive evidence that supplements improve mood or cognitive function, and it found mixed effects on sexual function and cardiovascular outcomes. However, most of these studies had small sample sizes or other limitations.

Early in 2016, initial results of the National Institutes of Health–supported Testosterone Trials were published in the New England Journal of Medicine.[4] More than 51,000 men were screened to enroll 790 men over age 65 with serum T levels < 275 ng/dL and evidence of sexual dysfunction, physical dysfunction, or reduced vitality. The intervention arm received 12 months of testosterone gel therapy to increase T levels to the mid-normal range for men aged 19-40. Compared with the placebo group, the testosterone gel group reported small increases in sexual activity, desire, and erectile function; slightly improved mood; but no differences in 6-minute walking distance or vitality.

In four recent papers in JAMA and JAMA Internal Medicine, the Testosterone Trial investigators reported the effects of the same supplement on coronary atherosclerosis, cognitive function, bone density, and unexplained anemia.[5,6,7,8] Testosterone had no effect on memory impairment, but it increased noncalcified coronary plaque volume on CT angiography and increased bone mineral density and hemoglobin levels. The follow-up period was not long enough to measure differences in cardiovascular events, fractures, or mortality.

Although the Testosterone Trials did not completely rule out benefits of screening for or treating low T, in my view these findings should discourage family physicians from intervening in the vast majority of older men. Most men with low T have no symptoms that will respond to supplements, and for those who do, there are safer and more effective drugs for erectile dysfunction, low bone density, and depression. Physicians who choose to prescribe testosterone supplements for age-related low T must inform patients that the US Food and Drug Administration considers such prescribing to be off-label and that they may have an increased risk for heart attack or stroke.[9]

In conclusion, I believe that the story of testosterone supplementation in older men may end up being similar to that of estrogen supplements in postmenopausal women: lots of early hype, but ultimately limited benefits and significant potential harms.

This has been Dr Kenny Lin for Medscape Family Medicine. Thank you for listening.


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