TRT and Cardiovascular Safety
The 2013-2015 Controversy, the FDA Label, and the TRAVERSE Resolution
Evidence grade 4 of 5, Strong. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- FDA added a CV-risk class warning in 2015; following TRAVERSE, the FDA in 2025-2026 moved to remove the limitation-of-use and revise CV language
Reference only. Not medical advice.
What can go wrong
TRAVERSE addressed MACE in men with or at high risk of cardiovascular disease but was a noninferiority design over a limited follow-up; it does not license unmonitored use. The atrial-fibrillation and pulmonary-embolism signals are real findings warranting attention, consistent with testosterone's thrombotic/hematocrit effects, and patients with prior VTE or afib risk deserve individualized counseling. Supraphysiological/anabolic dosing was not studied and is not reassured by TRAVERSE.
This is something to take to a clinician. The Atlas can tell you what is known about trt and cardiovascular safety 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.
Between 2013 and 2015 two observational studies, Vigen et al. (JAMA 2013) and Finkle et al. (PLoS ONE 2014), reported increased cardiovascular events with testosterone, triggering an FDA safety review and a 2015 class label warning of possible CV risk. Both studies were heavily criticized; the Vigen analysis notably reported reversed-direction results via unusual statistical handling, and a group of international experts publicly challenged the conclusions. The TRAVERSE trial (Lincoff et al., NEJM 2023), about 5,246 hypogonadal men at high CV risk randomized to testosterone gel or placebo, found testosterone noninferior to placebo for major adverse cardiac events (MACE), largely resolving the scare, while flagging numerically higher atrial fibrillation (3.5% vs 2.4%) and pulmonary embolism (0.9% vs 0.5%). By June 2026 the FDA moved to remove the age-related-hypogonadism limitation-of-use, citing TRAVERSE.
A decade-long scare built on two flawed studies, ended by a 5,200-man randomized trial, with two new asterisks.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
The plausible mechanisms cut both ways: testosterone can raise hematocrit (hyperviscosity/thrombosis), affect fluid balance and blood pressure, and influence platelets, but it can also improve body composition, insulin sensitivity, and exercise capacity. This biological ambiguity is exactly why observational data, prone to confounding by indication (sicker, more hypogonadal men), were inadequate, and why a randomized cardiovascular-outcomes trial was needed to separate signal from confounding.
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. The atrial-fibrillation and pulmonary-embolism signals from TRAVERSE warrant individualized counseling, especially with prior thromboembolism.
Replacement is not the same as a cycle
TRAVERSE studied replacement dosing targeting normal physiology. Its reassurance does not extend to supraphysiological/anabolic dosing, which is associated in observational data with cardiomyopathy, atherosclerosis, and thrombotic events and was not represented in the trial.
What it does to fertility
Cardiovascular safety is independent of fertility; TRT's fertility suppression is addressed separately via hCG/SERM strategies.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Cardiovascular risk assessment before initiation
- Hematocrit/hemoglobin (thrombotic-risk proxy)
- Blood pressure
- Symptom review for palpitations/afib and VTE signs
What people get wrong
Often saidStudies proved testosterone causes heart attacks
ActuallyThe 2013-2014 studies were observational and heavily criticized; the randomized TRAVERSE trial found testosterone noninferior to placebo for major adverse cardiac events.
Often saidTRAVERSE proves TRT is completely heart-safe for everyone
ActuallyTRAVERSE showed MACE noninferiority but flagged higher atrial fibrillation and pulmonary embolism, was time-limited, and did not study supraphysiological dosing.
Often saidThe FDA still warns that TRT causes heart attacks
ActuallyAfter TRAVERSE the FDA revised the CV language and in 2026 proposed removing the age-related-hypogonadism limitation-of-use; the strong 2015-era warning has been walked back.
Who profits, and who pushes back
International expert consensus (Androgen Study Group and others)
The Vigen and Finkle studies were methodologically flawed and confounded by indication; the testosterone-heart-attack narrative outran the evidence.
How we got here
The 'Low T' marketing boom of the late 2000s drove prescriptions sharply upward. In 2013-2014 Vigen and then Finkle reported CV harm; a widely covered observational analysis the same period also reported increased events in older men, and the press amplified a testosterone-heart-attack narrative. Andrology and cardiology experts countered that the studies were methodologically flawed and confounded by indication. The FDA convened an advisory committee, declined to find a definitive risk but in 2015 required a class CV-risk label and a limitation-of-use, and mandated a dedicated outcomes trial. TRAVERSE was that trial; its 2023 noninferiority result, followed by 2025-2026 FDA relabeling, closed the central controversy while leaving the afib/PE signals as open questions.
- 2013Vigen et al. (JAMA) reports increased CV events with testosterone
- 2014Finkle et al. (PLoS ONE) reports increased post-prescription MI; experts challenge both
- 2015FDA adds class CV-risk warning and limitation-of-use; requires confirmatory trial
- 2023TRAVERSE: MACE noninferior; afib and PE signals noted
- 2025-2026FDA revises CV language and removes the age-related-hypogonadism limitation-of-use
Set against the alternatives
The testosterone-cardiovascular story is a case study in how evidence grade determines a drug's regulatory fate. The 2013-2015 alarm rested entirely on observational data (Vigen, Finkle) that could not separate testosterone from the sicker, more comorbid men who tend to be prescribed it, classic confounding by indication. Compared with that evidence, TRAVERSE is categorically stronger: a randomized, double-blind, placebo-controlled outcomes trial in roughly 5,246 high-CV-risk hypogonadal men, the design the FDA itself had demanded. Where the observational studies implied harm, TRAVERSE found MACE noninferiority, which is why by 2025-2026 the FDA reversed course, removing the boxed warning and the age-related-hypogonadism limitation-of-use. The comparison is not symmetrical, however: TRAVERSE tested transdermal gel at replacement doses in a specific population, so it speaks to that use far more strongly than to injectable, supraphysiological, or non-hypogonadal use, where randomized CV data remain thin.
| Study | Year / Design | Direction of finding | Key limitation |
|---|---|---|---|
| Vigen et al. | 2013, observational (VA) | Suggested higher CV risk | Confounding by indication; disputed coding |
| Finkle et al. | 2014, pre/post claims | Higher post-Rx MI | No control group; healthy-user bias |
| FDA review | 2015, label action | Possible CV risk warning | Based on weak observational data |
| TRAVERSE | 2023, RCT (NEJM) | MACE noninferior | Excluded severe symptoms; gel only |
| FDA 2025-26 | Label/box removal | CV risk not supported | AFib/PE/fracture signals remain |
What we do not know
- Is the atrial-fibrillation signal causal, and what is the mechanism?
- Does the pulmonary-embolism signal reflect erythrocytosis, and who is most at risk?
- Long-term (beyond-trial) cardiovascular outcomes
What could change
Formulation-specific CV dataTRAVERSE used transdermal gel; injectable and oral (e.g. testosterone undecanoate) CV outcomes are less directly addressedAFib mechanism workInvestigating why testosterone modestly raised atrial fibrillation and thromboembolic events despite MACE neutralityFracture-risk follow-upThe TRAVERSE bone substudy showed higher fracture rates, prompting re-examination of testosterone and bone qualityLabel and guideline updatesEndocrine and urology societies revising CV-risk counseling after the 2025-2026 FDA label changesReal-world surveillancePost-label-change pharmacovigilance to confirm trial findings translate to broader, less-monitored telehealth populations
At a glance
- Vigen et al.
- JAMA 2013; observational; criticized, results in disputed direction
- Finkle et al.
- PLoS ONE 2014; pre/post-prescription MI comparison; confounded
- FDA action
- 2015 class label warning of possible CV risk; required confirmatory trial
- TRAVERSE
- Lincoff 2023; ~5,246 men; MACE noninferior (HR ~0.96)
- TRAVERSE signals
- Atrial fibrillation 3.5% vs 2.4%; PE 0.9% vs 0.5%
- 2026 FDA action
- Requested removal of the age-related-hypogonadism limitation-of-use, citing TRAVERSE
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about TRT and Cardiovascular Safety. A short entry is not a safe entry.
- 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.
- Where we land. We have not taken a position on this yet.
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
Vigen et al. (JAMA)2013
Observational; reported increased mortality/MI/stroke with testosterone; widely criticized for methodology and disputed result direction
Finkle et al. (PLoS ONE)2014
Reported higher non-fatal MI in the 90 days after a testosterone prescription vs the prior year; confounded by indication
TRAVERSE (Lincoff et al., NEJM)2023
MACE 7.0% vs 7.3% (HR ~0.96), noninferior; afib 3.5% vs 2.4%; PE 0.9% vs 0.5%