Written by Keen Meds · Reviewed by Licensed Clinical Providers · March 1, 2026
Key Insight: The TOM Trial enrolled men with mobility limitations and multiple cardiovascular risk factors — a deliberately high-risk population. The 23 vs. 5 cardiovascular event difference that stopped the trial has never been replicated in healthier, typical TRT candidate populations.
In July 2010, the New England Journal of Medicine published a study that alarmed clinicians who prescribed testosterone therapy. The Testosterone in Older Men with Mobility Limitations trial, known as the TOM Trial, had been stopped early by its data safety monitoring board after a significantly higher number of cardiovascular events appeared in the testosterone-treated group compared to men receiving placebo.
The study was small, the population was highly specific, and the trial ran for only about six months before being halted. Yet its impact on clinical practice and regulatory thinking was outsized for nearly a decade. Understanding exactly what the TOM Trial showed, and critically, what it could not show, provides important context for anyone evaluating the current evidence on testosterone therapy.
About the Study: Design and Why It Was Done
The TOM Trial was led by Shehzad Basaria and colleagues and published in the New England Journal of Medicine on July 8, 2010. The full title, Testosterone in Older Men with Mobility Limitations, describes the specific population the researchers intentionally targeted.
The rationale was straightforward: testosterone naturally declines with age, and older men with low testosterone also tend to have reduced muscle mass, lower physical function, and greater difficulty with mobility. Could testosterone therapy, by building muscle and improving physical capacity, help frail older men maintain independence and reduce fall and fracture risk?
The trial enrolled 209 men aged 65 and older. To qualify, participants had to have both low testosterone levels (defined as below 350 ng/dL or a low free testosterone) and mobility limitations, assessed by a formal physical performance battery. This was not a sample of generally healthy older men. To enter the trial, a man had to demonstrate measurable physical impairment.
Cardiovascular burden in the group was also substantial. Participants had high rates of pre-existing hypertension, hyperlipidemia, obesity, diabetes, and prior cardiovascular events. This was by design: the researchers wanted to study men who had the most to gain functionally from testosterone, but it meant the population carried significant baseline cardiac risk.
Men were randomized to receive either testosterone gel or placebo gel for a planned six months. The primary outcome being studied was physical function, specifically walking speed and stair-climbing power.
What the Study Found
The trial was stopped early by the data safety monitoring board after a planned interim safety review. At the time of stopping, 23 cardiovascular events had occurred in the testosterone group compared to 5 in the placebo group. The events included a mix of elevated blood pressure, arrhythmia, edema, and a smaller number of more serious events.
The relative imbalance was enough for the monitoring board to conclude the trial should not continue. This was the appropriate decision given the data, but stopping a trial early introduces its own statistical complications.
On the primary outcome of physical function, testosterone did show benefit. Men receiving testosterone had meaningfully greater improvements in leg press strength and stair-climbing power compared to placebo. The physical function finding was encouraging but was overshadowed in reporting and clinical reception by the safety signal.
The study also noted that the testosterone group showed greater increases in hemoglobin and hematocrit, which was expected given testosterone's stimulatory effect on red blood cell production. In men with underlying cardiovascular disease, elevated hematocrit can raise the risk of clotting events, which may have contributed to some of the adverse events observed.
What the Critics Said: Limitations and Context
The TOM Trial's limitations were significant and were acknowledged by its own authors. The most important issue is population specificity. The 209 men in this trial were selected precisely because they were old, physically impaired, and cardiovascularly burdened. Applying findings from this group to the broader population of men who consider testosterone therapy, typically middle-aged men with low energy, reduced libido, or mild body composition changes, involves a category error.
When a clinical trial stops early, statistical interpretation requires particular care. With only 209 total participants and 28 total cardiovascular events, the absolute numbers are small. Stopping early tends to overestimate the apparent effect size, because the interim data captured at an early stop may represent a particularly unfavorable snapshot rather than the true long-run effect.
The 23 vs. 5 event comparison also encompasses a heterogeneous mix of events. Elevated blood pressure and peripheral edema were included alongside more serious events. Grouping these together under a single count amplifies the apparent severity of the imbalance.
Multiple researchers noted that the TOM Trial answered an important question about this specific population rather than about testosterone therapy broadly. The signal it generated was real enough to warrant investigation in a larger, better-powered, longer-duration trial, which is exactly what eventually happened.
What This Means for You Today
The TOM Trial served a critical function: it established that in very high-risk elderly men with mobility limitations, testosterone therapy warranted careful monitoring and that a definitive, adequately powered randomized trial was necessary. It was one of the primary drivers behind the design and funding of the TRAVERSE trial.
TRAVERSE enrolled 5,246 men across 316 sites in 22 countries, followed them for a median of approximately 3.2 years, and specifically included men with pre-existing cardiovascular disease or elevated cardiovascular risk. Its primary result, a cardiovascular hazard ratio of 0.96 compared to placebo, did not replicate the TOM signal in a far larger and more rigorous study.
For men who are typical TRT candidates, those with confirmed low testosterone and symptoms such as fatigue, reduced libido, or difficulty maintaining muscle mass, the TOM Trial is not a reason to avoid treatment. It is a reason to undergo proper clinical evaluation, which includes a cardiovascular history review, baseline labs, and ongoing monitoring as treatment proceeds.
The combination of the TOM Trial's signal and the TRAVERSE trial's answer is how science is supposed to work. A smaller study identifies a concern. A larger, better-designed study provides a definitive answer. The answer here, across more than 5,000 men and more than three years of follow-up, is that testosterone therapy does not significantly increase major cardiovascular event risk in men with hypogonadism.
Frequently Asked Questions
Why was the TOM Trial stopped early?
The data safety monitoring board stopped the trial after observing 23 cardiovascular events in the testosterone group versus 5 in the placebo group at an interim review. With an anticipated six-month duration and 209 participants, the monitoring board determined the imbalance warranted stopping rather than continuing.
Does the TOM Trial mean testosterone therapy is dangerous for older men?
The TOM Trial studied a highly specific population: men aged 65 and older with both mobility limitations and substantial pre-existing cardiovascular burden. The findings apply most directly to that profile. The TRAVERSE trial, which followed over 5,000 men including many with cardiovascular risk factors for over three years, found no significant increase in major cardiovascular events.
What is a data safety monitoring board?
A data safety monitoring board (DSMB) is an independent committee of experts that reviews accumulating trial data at pre-specified intervals. The DSMB's role is to protect participants by stopping a trial early if there is clear evidence of harm or benefit that makes continuation unnecessary or unsafe. Stopping early is appropriate when it happens, but it can make smaller studies harder to interpret statistically.
Did the TOM Trial show that testosterone helps physical function?
Yes. Despite the safety signal, the testosterone group showed significantly greater improvements in leg press strength and stair-climbing power compared to placebo. The trial supported the hypothesis that testosterone can improve physical performance in hypogonadal older men, though the cardiovascular signal in this particular population raised concerns that prevented a clear clinical recommendation.
What the Research Means for Your Treatment Options
The TOM Trial raised an important safety question about testosterone therapy in frail, cardiovascularly burdened elderly men. That question was answered by the TRAVERSE trial, which confirmed testosterone therapy does not meaningfully increase major cardiovascular event risk across a much larger and more diverse population of hypogonadal men. The science moved forward as it should, and the current evidence base supports safe use of testosterone therapy in appropriately selected men.
Keen Meds connects you with licensed clinical providers for a telehealth evaluation and lab review. If your testosterone is clinically low, you may qualify for Testosterone Spray Rx, a needle-free transdermal testosterone program.
