CATEGORY: MEN’S HEALTH
Middle-aged and older men with low testosterone who used a daily testosterone gel broke a bone 43% more often than men using a placebo gel—3.50% versus 2.46% over a median of just over three years, or 91 fractures among 2,601 men on testosterone against 64 among 2,603 on placebo—in a randomized trial published in the New England Journal of Medicine.1 The investigators had designed the study expecting the hormone to prevent fractures. It did the opposite.
Five Thousand Men, a Daily Gel, and Every Broken Bone Recorded
The trial, called TRAVERSE, enrolled 5,204 men aged 45 to 80 whose testosterone measured below 300 ng/dL on two separate morning blood samples, who had symptoms of low testosterone, and who either had heart disease or were at high risk of it. Each was assigned by chance to a daily testosterone gel or to an identical placebo gel, with the dose adjusted to keep blood levels in the normal range; because chance rather than choice decided who got the hormone, the two groups were alike in everything else, and a difference at the end can be credited to the treatment. Testosterone levels in the treated group rose from a median of 227 ng/dL at the start to 368 ng/dL at six months and stayed above baseline for three years. Adherence to the gel was about 90% in both groups. Participants were enrolled between 2018 and 2022 and followed for a median of 3.19 years, during which every fracture they reported was checked against medical records and confirmed before it was counted. The question the fracture analysis set out to answer was whether testosterone would reduce those confirmed clinical fractures.
One Extra Fracture per Hundred Men in Three Years
Confirmed fractures occurred in 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—a 43% higher relative risk. By the three-year mark the cumulative incidence was 3.8% on testosterone and 2.8% on placebo. In plain terms, picture a full commuter bus carrying 100 men from the trial: over three years, about three of them on placebo would break a bone, and about four on testosterone. The absolute difference is small and the relative increase is real, and both halves of that sentence matter. The most common breaks were of the ribs, wrist and ankle, and more than 80% of fractures in both groups happened with some trauma, mostly a fall. When the investigators looked only at fractures that did not involve high-impact trauma, the excess on testosterone 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.
The Result the Investigators Did Not Expect
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.” That is why the fracture analysis was built into the trial in the first place: testosterone raises bone density in men with low levels, and the reasonable assumption was that denser bone would mean fewer breaks. The authors wrote that the mechanism is unclear and might involve an adverse effect of testosterone on cortical bone, the dense outer shell of a bone. Two endocrinologists writing an accompanying editorial offered a different reading: the fracture curves separated early, which they judged too fast to be explained by a change in bone itself, and the excess was concentrated in ankle and rib fractures that came with trauma rather than in the classic osteoporotic fractures of the hip and spine.2 Their suggestion was behavioral—men who feel stronger and more energetic on testosterone may take on more physical activity, and with it more falls and impacts. The trial cannot settle which explanation is right; it can only say that the expected protection did not appear.
The Same Trial Found the Heart Was Not Harmed, but Other Risks Rose
The fracture result is one of several from TRAVERSE, which was run primarily to answer a different question: whether testosterone treatment raises the risk of heart attack and stroke. On that main question, published in 2023, the answer was reassuring—major cardiovascular events occurred in 7.0% of men on testosterone and 7.3% on placebo, meeting the trial’s standard for no increased heart risk.3 But the same report found more atrial fibrillation (an irregular heart rhythm), more pulmonary embolism (a blood clot in the lungs) and more acute kidney injury among men on testosterone. The fracture finding adds a fourth item to that list. Taken together, the trial’s picture of testosterone treatment in men with low levels is of a therapy that does not endanger the heart but carries several distinct risks that were not obvious before, and that does not deliver the bone protection long assumed for it.
Key Takeaways
- In men aged 45 to 80 with low testosterone, a daily testosterone 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.
- The researchers expected fewer fractures, because testosterone increases bone density; the trial found the opposite, and the mechanism is not known.
- Most of the excess fractures involved trauma such as a fall, and the editorial’s leading explanation is that treated men became more active rather than that their bones weakened.
- Because men were assigned by chance, the trial can attribute the difference to testosterone itself; the same trial found no increase in heart attacks or strokes but more atrial fibrillation, lung clots and kidney injury.
References
- Snyder PJ, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. New England Journal of Medicine. 2024;390(3):203–211. link
- Grossmann M, Anawalt BD. Breaking News — Testosterone Treatment and Fractures in Older Men. New England Journal of Medicine. 2024;390(3):267–268. link
- 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