Men on Testosterone Therapy Broke Bones More Often Than Men on Placebo

CATEGORY: MEN’S HEALTH

The fracture analysis inside the TRAVERSE trial was built to show that testosterone protects aging bone. It showed the reverse. Middle-aged and older men with low testosterone who used a daily hormone gel broke a bone 43% more often than men using a placebo gel: 3.50% against 2.46% over a median of just over three years. That is 91 fractures among 2,601 men on testosterone and 64 among 2,603 on placebo, in a trial published in the New England Journal of Medicine.¹

Five Thousand Men, and Every Break Checked Against the Records

TRAVERSE enrolled 5,204 men aged 45 to 80. Each had symptoms of low testosterone and a blood level under 300 ng/dL on two separate morning samples, and each either had heart disease or stood at high risk of it. A randomization list, not a doctor’s judgment, decided who rubbed on a daily testosterone gel and who got an identical placebo. That is what lets the trial pin any difference at the end on the hormone. Doses were adjusted to hold blood levels in the normal range. Among treated men the median climbed from 227 ng/dL at the start to 368 ng/dL by six months and stayed above baseline for three years. Roughly 90% of both groups kept using their gel. Enrollment ran from 2018 to 2022, and follow-up lasted a median of 3.19 years. Every fracture a man reported was confirmed against his medical records before it was counted.

One Extra Break per Hundred Men in Three Years

Confirmed fractures reached 91 men on testosterone (3.50%) and 64 on placebo (2.46%), a hazard ratio of 1.43 with a 95% confidence interval of 1.04 to 1.97. In relative terms that is 43% more risk. By the three-year mark the cumulative incidence stood at 3.8% against 2.8%. Picture a commuter bus carrying 100 men from the trial. Over three years about three of them on placebo break a bone, and about four on testosterone. The absolute difference is small. The relative increase is real. Ribs, wrists and ankles were the commonest breaks, and more than 80% of fractures in both groups arrived with some trauma, usually a fall. Counting only fractures without high-impact trauma, the excess was of similar size but no longer statistically clear: a hazard ratio of 1.32, with a confidence interval of 0.94 to 1.86 that includes no difference at all.¹

Denser Bone Was Supposed to Mean Fewer Breaks

Lead investigator Peter Snyder said plainly, “We did not expect these results, because most previous studies showed that testosterone improved many measures of bone structure and quality.” Testosterone does raise bone density in men who are short of it, which is why a fracture analysis was written into the trial from the outset. The authors say the mechanism behind the excess is unclear and might involve damage to cortical bone, the dense outer shell that gives a bone its strength. Two endocrinologists read the numbers differently in an accompanying editorial.² They pointed out that the fracture curves parted early, too fast in their judgment to reflect a change in bone itself, and that the excess sat in ankle and rib breaks that came with trauma rather than in the hip and spine fractures typical of thinning bone. Their alternative explanation is behavioral. Men who feel stronger and more energetic may simply do more, and doing more brings more falls and impacts. The trial cannot choose between the two readings. It can only report that the expected protection never appeared.

The Rest of What TRAVERSE Turned Up

Fractures were never the main question. TRAVERSE was built above all to ask whether testosterone treatment raises the risk of heart attack and stroke, and the 2023 answer was reassuring: major cardiovascular events occurred in 7.0% of treated men and 7.3% of men on placebo, meeting the trial’s standard for no added heart risk.³ The same report counted more atrial fibrillation, an irregular heart rhythm, along with more pulmonary embolism, a blood clot in the lungs, and more acute kidney injury. Fractures make a fourth entry on that list. The trial’s overall portrait of testosterone treatment in men with low levels is of a therapy that leaves the heart alone, carries several risks nobody had pinned down before, and does not deliver the bone protection long assumed for it.

Key Takeaways

• Among men aged 45 to 80 with low testosterone, a daily gel was followed by 43% more confirmed fractures than placebo over about three years: 3.50% versus 2.46%, roughly one extra fracture per hundred men.
• Most of the extra fractures involved trauma such as a fall. The editorial’s leading explanation is that treated men became more active, not that their bones weakened.
• Researchers expected fewer breaks, because testosterone raises bone density. Why the opposite happened is not known.
• The men did not pick their own gel, so the fracture gap can be put down to testosterone itself. The same trial found no increase in heart attacks or strokes, but more atrial fibrillation, lung clots and kidney injury.

References

1. Snyder PJ, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. New England Journal of Medicine. 2024;390(3):203–211. link
2. Grossmann M, Anawalt BD. Breaking News — Testosterone Treatment and Fractures in Older Men. New England Journal of Medicine. 2024;390(3):267–268. link
3. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023;389(2):107–117. link