Cardiovascular Risk, Historical and Current
From the FDA Black-Box Era to TRAVERSE and the 2025 Label Change
Evidence grade 4 of 5, Strong. Read how the Atlas grades evidence.
1 human trial, ~5,246 participants (TRAVERSE). The written rationale for this grade is still being prepared.
- FDA
- FDA boxed-warning revised (Feb 2025) following TRAVERSE; new blood-pressure warning added
Reference only. Not medical advice.
What can go wrong
The current evidence supports cardiovascular neutrality of physiological-dose testosterone in confirmed hypogonadal men, but with important caveats: TRAVERSE noted increased atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone arm. The neutral finding does not extend to men without true hypogonadism, to supraphysiological/anabolic dosing, or to unmonitored use. Supraphysiological androgen exposure has a separate, poorly quantified, and concerning cardiovascular profile (see Anabolic Steroid Health Consequences).
This is something to take to a clinician. The Atlas can tell you what is known about cardiovascular risk, historical and current 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.
Cardiovascular safety of testosterone therapy is the most consequential and most revised question in the field. Early-2010s observational studies and trials suggested elevated cardiovascular risk, prompting an FDA safety communication and class labeling in 2015. The TRAVERSE randomized trial (2023, ~5,200 men with hypogonadism and high cardiovascular risk) found testosterone non-inferior to placebo for major adverse cardiac events at physiological doses. In February 2025 the FDA revised the class-wide labeling to remove the cardiovascular language from the Boxed Warning, while simultaneously requiring a new warning about increased blood pressure based on postmarket ambulatory blood-pressure monitoring studies. Supraphysiological dosing was not studied and carries a different, understudied risk profile.
The cardiovascular story of TRT was rewritten between 2013 and 2025.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
Proposed mechanisms for cardiovascular harm at the time of the early warnings included erythrocytosis (increased viscosity/thrombosis), effects on lipids, blood pressure, and platelet aggregation. TRAVERSE was designed as a cardiovascular outcomes (non-inferiority) trial in hypogonadal men with established cardiovascular disease or high risk, using a transdermal gel titrated to mid-physiological levels. It did find a higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone arm, secondary signals warranting attention even amid the neutral primary MACE result.
Safety in detail
This intervention involves significant physiological effects and requires evaluation and monitoring by a qualified physician. Cardiovascular safety data apply to physiological dosing in confirmed hypogonadism; supraphysiological dosing is understudied. Self-administration without medical oversight carries documented health risks.
Replacement is not the same as a cycle
TRAVERSE studied physiological-dose testosterone titrated to mid-normal levels. It says nothing reassuring about supraphysiological or anabolic dosing, which is associated with left ventricular hypertrophy, adverse lipids, and sudden cardiac death in case series.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Baseline cardiovascular risk assessment
- Hematocrit monitoring
- Blood pressure (FDA 2025 labeling warns of testosterone-associated BP increases)
- Awareness of atrial fibrillation, VTE, and renal signals seen in TRAVERSE
What people get wrong
Often saidTRT causes heart attacks
ActuallyThe early observational signal was not confirmed by the randomized TRAVERSE trial, which found cardiovascular non-inferiority at physiological doses in hypogonadal men. The FDA removed the cardiovascular language from the Boxed Warning in 2025, though it added a new warning about increased blood pressure.
Often saidTRAVERSE proves testosterone is good for the heart
ActuallyTRAVERSE showed non-inferiority (not benefit) for major cardiac events, and flagged increased atrial fibrillation, pulmonary embolism, and acute kidney injury. It studied physiological doses in confirmed hypogonadism only.
Who profits, and who pushes back
TRAVERSE interpretation critics
Caution that the trial had high discontinuation and lost-to-follow-up rates, short mean treatment duration (~22 months), and tested only modest replacement doses, limiting how far reassurance can extend.
Steven Nissen and colleagues
Emphasize that the secondary signals for atrial fibrillation, pulmonary embolism, and acute kidney injury are real and warrant caution despite the neutral primary MACE result.
Generalizability skeptics
Stress that findings apply only to symptomatic, confirmed hypogonadal men and say nothing about supraphysiologic dosing or testosterone use in men with normal levels.
Set against the alternatives
The reversal here is instructive: a cardiovascular signal generated by observational data and amplified by regulatory action was substantially overturned by a purpose-built randomized outcomes trial. The lesson is dose- and population-specific, neutrality applies to physiological replacement in genuine hypogonadism, not to supraphysiological use or to men with normal baseline testosterone.
| Marker | Physiologic TRT | Supraphysiologic AAS | Note |
|---|---|---|---|
| MACE (composite) | Noninferior in TRAVERSE | Not studied in RCTs | Different populations |
| Hematocrit | Mild rise, monitored | Marked erythrocytosis | Viscosity/thrombosis risk |
| Blood pressure | Small increase (label warning) | Often elevated | New FDA BP warning |
| HDL cholesterol | Modest change | Sharp suppression | Dose-dependent |
| Atrial fibrillation | Higher vs placebo | Reported in users | TRAVERSE signal |
| Cardiac structure | Generally neutral | LV hypertrophy reported | Long-term unclear |
What we do not know
- Why did TRAVERSE show higher atrial fibrillation, pulmonary embolism, and acute kidney injury despite neutral MACE?
- Do the new blood-pressure warnings translate into long-term cardiovascular harm?
- What is the cardiovascular risk of supraphysiologic dosing, which no RCT has tested?
- Does route of administration (gel vs injection vs pellet) alter cardiovascular risk?
- How should the secondary thrombotic signals change patient selection and monitoring?
What could change
Mechanistic substudiesProbing the afib, PE, and AKI signals from TRAVERSE for causal pathwaysAmbulatory BP monitoringRoutine blood-pressure surveillance informed by postmarket studiesFormulation comparisonsHead-to-head cardiovascular data across delivery routesSupraphysiologic safetyCalls for dedicated study of high-dose and enhancement use, currently a data void
At a glance
- Pivotal RCT
- TRAVERSE (NEJM 2023)
- TRAVERSE size
- ~5,246 men
- FDA action
- Boxed-warning CV language removed Feb 2025; BP warning added
- Caveat
- Physiological dose in confirmed hypogonadism only
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about Cardiovascular Risk, Historical and Current. 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, observational VA cohort2013
Reported association between testosterone therapy and increased mortality/MI/stroke; later heavily critiqued methodologically
Finkle et al., PLoS ONE, claims-based study2014
Reported increased rate of non-fatal MI in the period after a testosterone prescription, especially in older men
FDA Drug Safety Communication2015
Required class labeling on possible cardiovascular risk and restricted approved indication to classical hypogonadism
Lincoff et al. (TRAVERSE), NEJM2023
Testosterone gel non-inferior to placebo for MACE in hypogonadal men at high cardiovascular risk; secondary increases in AFib, PE, and AKI
FDA testosterone labeling revision2025
Removed cardiovascular language from the Boxed Warning based on TRAVERSE, added a new blood-pressure warning from postmarket ABPM studies, and retained hematocrit and other monitoring guidance