One year after TRAVERSE: what the landmark cardiovascular safety trial changed in TRT prescribing.

The trial in one paragraph

TRAVERSE randomized 5,246 men aged 45–80 with hypogonadism (two low morning testosterone readings plus symptoms) and either pre-existing cardiovascular disease or elevated cardiovascular risk factors to receive either testosterone gel or placebo gel. Mean follow-up was 33 months. This was the trial the field had been waiting for since the 2010s, when smaller and retrospective studies produced conflicting signals about whether testosterone therapy raised cardiovascular risk — a question that had kept some clinicians cautious and some patients undertreated for over a decade.

Primary endpoint

The primary endpoint was time to first occurrence of a composite of MACE — death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. TRAVERSE was designed as a non-inferiority trial with a pre-specified margin of 1.5 for the upper bound of the confidence interval.

Secondary findings that changed practice

The primary result was reassuring. The secondary safety findings are why TRAVERSE still shapes how careful clinics practice today. Compared to placebo, men on testosterone showed statistically higher rates of:

• Atrial fibrillation — the most consistent secondary signal, now a standard part of pre-treatment cardiac history screening.
• Pulmonary embolism — an uncommon but serious finding that changed how clinics handle patients with a personal or strong family history of clotting disorders.
• Acute kidney injury — a less-discussed but real signal that reinforces the value of baseline and periodic renal function monitoring (part of a standard CMP).

None of these findings reversed the primary non-inferiority result on MACE. They did, however, give the field concrete, trial-grade evidence for exactly which patients need extra scrutiny before and during treatment — which is a meaningfully different, more precise picture than the vague "testosterone might be risky for your heart" framing that dominated the pre-TRAVERSE era.

How Endocrine Society and AUA guidelines updated

Professional guidance from the Endocrine Society and the American Urological Association (AUA) predates TRAVERSE (2018), but both bodies' subsequent clinical guidance and practice updates in the years following the trial's 2023 publication have incorporated its findings — reinforcing the existing emphasis on baseline cardiovascular risk assessment, hematocrit monitoring, and structured follow-up, while removing blanket cardiovascular contraindication language that had been more conservative in the pre-TRAVERSE era for men with controlled risk factors.

How Aurafil applies this

TRAVERSE isn't an academic footnote for us — it's built into intake and monitoring:

• Cardiovascular risk screening at intake. Personal and family history of MI, stroke, atrial fibrillation, and venous thromboembolism is reviewed before any prescription decision.
• Hematocrit monitoring every 3–6 months. Elevated hematocrit is a distinct clotting risk pathway from what TRAVERSE studied, but it compounds the same concern — we treat it as non-negotiable.
• A-fib history is a red flag, not an automatic disqualifier. It prompts closer cardiology coordination and more conservative dosing, not blanket denial.
• Personal history of pulmonary embolism requires an anticoagulation consult before we proceed, given TRAVERSE's PE signal.

What TRAVERSE didn't answer

No single trial answers every question, and TRAVERSE has real, acknowledged limits:

• Long-term (10+ year) safety — 33 months mean follow-up is substantial for an RCT, but it doesn't speak to risk over a decade or more of continuous therapy.
• Injectable testosterone wasn't studied — the trial used a topical gel. Injectable esters (cypionate, enanthate) produce a different pharmacokinetic profile, and results don't automatically generalize.
• Younger men without cardiovascular risk factors were not the study population — TRAVERSE enrolled men 45–80 with existing CV disease or risk factors, not the broader population of younger hypogonadal men without those risks.

Good clinical practice treats TRAVERSE as the strongest available evidence on a specific question — not as a blanket safety certificate for every formulation, dose, and patient population.