The Testosterone in Older Men with Mobility Limitations trial was stopped early on the recommendation of its data and safety monitoring board, because there was a significantly higher rate of adverse cardiovascular events in the testosterone group. At termination, 209 men had been enrolled. 23 men on testosterone had cardiovascular-related adverse events against 5 on placebo.[1]
That is the finding that reshaped testosterone prescribing for the next decade. The rest of this page is about what it does and does not support — including the limitation the authors themselves wrote into their conclusion.
What TOM studied
The trial was designed to test whether testosterone improved mobility in older men who had lost it. Safety and efficacy of testosterone in older men with limitations in mobility had not been studied.[1]
- Participants: community-dwelling men 65 years or older with limitations in mobility, and a total serum testosterone of 100–350 ng/dL, or free testosterone below 50 pg/mL.
- Intervention: testosterone gel or placebo gel, applied daily, intended for 6 months.
- Enrolled at termination: 209 men, mean age 74.
- Baseline: a high prevalence of hypertension, diabetes, hyperlipidemia and obesity among participants.[1]
That last line is not a footnote. This was a frail, comorbid population selected for mobility limitation — not a general population of men considering testosterone therapy.
What it found
Harms. The testosterone group had higher rates of cardiac, respiratory and dermatologic events than placebo. 23 subjects on testosterone versus 5 on placebo had cardiovascular-related adverse events, and the relative risk remained constant across the 6-month treatment period.[1]
Benefits. The same trial found what it set out to look for: compared with placebo, the testosterone group had significantly greater improvements in leg-press and chest-press strength, and in stair climbing while carrying a load.[1]
TOM is almost never cited for that half. The trial that produced the cardiovascular scare also produced clean evidence that testosterone improved strength and functional capacity in men who had lost both.
The sentence that usually gets dropped
The authors' conclusion contains its own limitation, stated without hedging:
In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.[1]
A trial's authors telling you not to generalise their safety finding is unusual, and it should carry weight in both directions. It does not mean the signal was noise. It means 209 frail men over six months cannot settle a question about cardiovascular risk in the population actually being prescribed testosterone.
Why an early stop makes a finding look stronger than it is
Trials stopped early for harm tend to overstate the size of the harm. The stopping rule fires when the accumulated difference is at its most extreme, and stopping at that moment freezes the estimate there rather than letting it regress as more data accumulate.
Combined with small numbers — 23 events against 5 — the point estimate is unstable even though the direction was real enough to end the trial. Ending a trial early is the correct response to a safety signal. It is also a guarantee that the resulting number is the least reliable version of itself.
What happened next
TOM did not stay a single trial. It became the first item in a sequence: an observational analysis and a meta-analysis in 2013,[2][3] then a class-wide FDA labeling change. The whole arc is in the controversy years, and the narrative treatment is the trial that was stopped early.
Thirteen years later, TRAVERSE enrolled 5,246 men with cardiovascular disease or high risk of it, powered specifically for major adverse cardiac events — the trial TOM was never designed to be.[4]
Basaria himself set out the wider clinical picture four years after TOM, in a Lancet seminar whose list of men who should not be treated has needed less revision than the cardiovascular estimates around it.
Bottom line
TOM found more cardiovascular adverse events on testosterone in 209 frail older men over six months, and it found real gains in strength and stair-climbing in the same men. It was stopped early, which was correct, and which makes its effect estimate the least stable one available.
Its authors said explicitly that its size and population prevent broader inferences about the safety of testosterone therapy. Anyone citing TOM as proof that testosterone causes heart attacks is quoting past that sentence.
References
4 sources
- Basaria S, Coviello AD, Travison TG, et al. Adverse Events Associated with Testosterone Administration. N Engl J Med. 2010;363(2):109–122. doi:10.1056/NEJMoa1000485 · PMID 20592293
- Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829–1836. doi:10.1001/jama.2013.280386 · PMID 24193080
- Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108. doi:10.1186/1741-7015-11-108 · PMID 23597181
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322
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