TRAVERSE in the Aging-Men Context
Cardiovascular Safety RCT, the Fracture Signal, and What It Did and Did Not Show
Evidence grade 5 of 5, Settled. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- Informed the February 2025 FDA removal of the testosterone cardiovascular boxed warning; indication remains restricted to medically-caused hypogonadism
Reference only. Not medical advice.
What can go wrong
Even at replacement doses in a monitored RCT, testosterone showed higher atrial fibrillation, acute kidney injury, pulmonary embolism, and clinical fractures versus placebo. These do not negate cardiovascular reassurance but undercut any framing of TRT as risk-free, particularly in the much lower-risk, younger 'optimization' population that marketing targets.
This is something to take to a clinician. The Atlas can tell you what is known about traverse in the aging-men context in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
TRAVERSE (Lincoff et al., NEJM 2023) was the FDA-mandated cardiovascular safety trial: 5,246 men aged 45-80 with hypogonadal symptoms, two morning testosterone levels under 300 ng/dL, and established or high cardiovascular risk, randomized to transdermal 1.62% testosterone gel or placebo. Over ~22 months mean follow-up, testosterone was noninferior for major adverse cardiovascular events (MACE), reassuring after a decade of CV concern. But the trial also flagged higher rates of atrial fibrillation, acute kidney injury, pulmonary embolism, and, in a companion fracture analysis, MORE clinical fractures in the testosterone group, a paradox given testosterone's known boost to bone density. TRAVERSE studied symptomatic hypogonadal men, not healthy men seeking enhancement.
Reassuring on the heart, not a green light for 'optimization', and it raised new questions.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, analyzed for noninferiority. Testosterone was titrated to a mid-normal range (~350-750 ng/dL), making this a replacement-dose, not supraphysiologic, trial. The fracture finding is mechanistically unexplained: testosterone reliably increases bone mineral density, so a higher fracture count was unexpected and is being scrutinized (possible behavioral, fall-risk, or chance explanations).
What TRAVERSE did NOT show
TRAVERSE enrolled symptomatic men with confirmed low testosterone and high cardiovascular risk; it does not license testosterone for healthy aging men with normal levels seeking energy, muscle, or longevity. Noninferiority is not the same as benefit, and it was bounded by the trial's design and adherence (substantial discontinuation occurred). The afib, AKI, PE, and fracture signals are real cautions that 'optimization' marketing tends to omit.
Safety in detail
This intervention involves significant physiological effects and requires evaluation and monitoring by a qualified physician. Self-administration without medical oversight carries documented health risks.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Hematocrit (erythrocytosis risk)
- Cardiovascular status and arrhythmia symptoms
- PSA and prostate symptoms
- Testosterone level (target mid-normal, avoid supraphysiologic peaks)
- Fall/fracture risk in older men
What people get wrong
Often saidTRAVERSE proves testosterone is safe for any man
ActuallyIt studied symptomatic, biochemically deficient men at high cardiovascular risk and showed CV noninferiority, not benefit, and not safety for healthy men seeking enhancement.
Often saidTestosterone strengthens bones, so it must cut fractures
ActuallyTRAVERSE's companion analysis found MORE fractures on testosterone despite the known density increase, a still-unexplained paradox.
Who profits, and who pushes back
TRAVERSE limitation reviewers
Point to substantial treatment discontinuation and incomplete follow-up that complicate intention-to-treat interpretation of the neutral cardiovascular result.
Peter Snyder and fracture-substudy authors
Report that testosterone did not reduce and may have modestly increased clinical fractures, contradicting expectations from its bone-density benefit and leaving the mechanism unresolved.
Generalizability critics
Stress the cohort was symptomatic, high-cardiovascular-risk hypogonadal men, so results should not be extrapolated to healthy older men seeking testosterone for vitality or enhancement.
Set against the alternatives
TRAVERSE is the largest and most rigorous testosterone cardiovascular outcomes trial to date, dwarfing the earlier observational studies and small RCTs that drove the 2010s safety alarms. Unlike those analyses, it was a prospective, placebo-controlled, FDA-mandated noninferiority trial with central event adjudication, which is why its neutral MACE result reshaped labeling. But it tested only mid-normal replacement dosing in confirmed hypogonadism, so it does not speak to supraphysiologic or enhancement use, and its fracture and thrombotic signals mean it offers a more nuanced verdict than a simple clean bill of health.
| Outcome domain | TRAVERSE finding | Direction vs placebo | Interpretation |
|---|---|---|---|
| MACE (primary) | Noninferior | Neutral | Reassuring at replacement dose |
| Clinical fractures | ~3.8% vs 2.8% at 3 yr | Higher with T | Unexpected, unexplained |
| Atrial fibrillation | 3.5% vs 2.4% | Higher with T | Secondary signal |
| Pulmonary embolism | 0.9% vs 0.5% | Higher with T | Thrombotic caution |
| Acute kidney injury | 2.3% vs 1.5% | Higher with T | Secondary signal |
| PSA / prostate | No major excess cancer | Neutral | Monitoring still advised |
What we do not know
- Why did fractures increase despite higher bone density, and is it causal or chance?
- Do the afib/AKI/PE signals generalize to lower-risk 'optimization' users not represented in the trial?
- Does CV noninferiority in deficient men say anything about net benefit in men with normal levels? (No data.)
What could change
Fracture mechanismInvestigations into fall risk, behavior, or chance behind the paradoxical fracture signalLonger follow-upExtended outcome tracking to test durability of the neutral MACE resultSubgroup analysesIdentifying which older men benefit versus face elevated thrombotic riskHealthy-aging trialsOpen question whether findings replicate in non-hypogonadal older men
At a glance
- Trial
- TRAVERSE (Lincoff et al., NEJM 2023)
- Participants
- 5,246 men, ages 45-80
- Entry T
- Two morning levels <300 ng/dL + symptoms
- Population
- Pre-existing or high CV risk
- Intervention
- 1.62% transdermal testosterone gel vs placebo
- Primary result
- Noninferior for MACE
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about TRAVERSE in the Aging-Men Context. A short entry is not a safe entry.
- Timeline. We have not built the dated record of research and regulatory events.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- Children and teenagers. We have not checked what is known about younger people.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
TRAVERSE primary CV results, Lincoff et al., NEJM2023
Testosterone noninferior to placebo for MACE in 5,246 high-CV-risk hypogonadal men; higher afib, AKI, and pulmonary embolism observed
TRAVERSE fracture analysis, Snyder et al., NEJM2024
MORE clinical fractures in the testosterone group than placebo, an unexpected reversal of testosterone's bone-density benefit
FDA labeling action2025
Removed the class-wide cardiovascular boxed warning citing TRAVERSE, while retaining the restricted (medically-caused hypogonadism) indication