TRT and Your Heart — Does Testosterone Therapy Raise Heart Attack Risk?
For a decade, testosterone therapy operated under the shadow of an FDA warning about heart attack risk. The large randomized TRAVERSE trial from 2023 finally gave a clear answer — though not as simple as the headlines suggested. We walk through the whole story, from controversial observational studies to where the evidence stands today.
Number of studies
4
Safety
Requires caution
Time to effects
Not applicable in the sense of a therapeutic effect — this entry describes a cardiovascular risk profile, established in a trial that averaged about 22 months of treatment and 33 months of follow-up.
Who it's for
Table of contents
TL;DR
For a decade, testosterone therapy operated under the shadow of an FDA warning about heart attack risk. The large randomized TRAVERSE trial from 2023 finally gave a clear answer — though not as simple as the headlines suggested. We walk through the whole story, from controversial observational studies to where the evidence stands today.
- →The large, randomized TRAVERSE trial gave a clear answer where a decade earlier there was only uncertain observational data
- →The results let doctors and patients make TRT decisions without unwarranted fear of a heart attack based on outdated, methodologically weak studies
- →The 2025 removal of the FDA warning opens access to therapy for men with cardiac history who were previously refused treatment out of caution
| Research question | Does TRT increase the risk of heart attack, stroke, and cardiovascular death |
|---|---|
| Early warning signals | Vigen et al. 2013 (JAMA), Finkle et al. 2014 (PLOS ONE) — observational studies |
| Regulator response | FDA boxed warning introduced in 2015 |
| Definitive trial | TRAVERSE, Lincoff et al. 2023, New England Journal of Medicine |
| TRAVERSE trial type | Large, randomized, placebo-controlled, commissioned by the FDA (>5,200 men) |
| TRAVERSE primary result | Testosterone non-inferior to placebo for major cardiovascular events (MACE) |
| Important caveat | More frequent atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone group |
| FDA warning status | Cardiovascular risk warning removed from labels in 2025 following TRAVERSE results |
| Level of evidence | Strong — based on a large RCT designed specifically to answer this question |
Understand
Overview
Whether testosterone therapy raises the risk of a heart attack, stroke, or cardiovascular death has, for more than a decade, been one of the most contested questions in all of endocrinology. This wasn't an academic dispute without consequences — from 2013 to 2023, millions of men worldwide made the decision to start or continue TRT under the shadow of an official warning from the American drug regulator, and many physicians refused to prescribe therapy to patients with any cardiac history at all, fearing real harm.
The history of this dispute is an instructive case study in how medical science arrives at the truth — through preliminary, imperfect data, public alarm, years of debate, and finally a trial designed specifically to settle the question once and for all. In 2013 and 2014, two large but observational analyses suggested that men on TRT might face a higher risk of heart attack, stroke, and death. Widely covered in the media, these results led to an official safety communication from the U.S. Food and Drug Administration (FDA) and to a boxed warning added to product labeling in 2015. The endocrinology community, however, pointed out serious methodological weaknesses in these studies from the start — and because observational data can't by nature distinguish causation from coincidence, the only path to a trustworthy answer was a large, randomized clinical trial.
That trial — TRAVERSE — was ultimately conducted at the FDA's own request and published in 2023 in the New England Journal of Medicine. It included more than five thousand men with hypogonadism and existing or elevated cardiovascular risk — exactly the population the concerns centered on most. The result was unambiguous on the primary endpoint: testosterone didn't increase the risk of major cardiovascular events relative to placebo. That finding, based on hard data from a randomized trial rather than correlations from registries, is now the foundation of the modern approach to TRT safety. At the same time, TRAVERSE revealed other, less publicized signals — more frequent atrial fibrillation, pulmonary embolism, and acute kidney injury in the treated group — which rule out any oversimplified claim that testosterone is "completely safe for the heart" in every sense of the word.
This entry walks through the full chronology of this debate: from the first warning signals, through years of uncertainty and conflicting meta-analyses, to the final TRAVERSE data and what it means in practice for a man considering or already on testosterone therapy.
Mechanism of action
Before getting into the history of the studies, it's worth understanding why the question of testosterone and the heart was biologically plausible in the first place — it didn't come out of nowhere. Testosterone affects the cardiovascular system through several parallel pathways, some of which could theoretically increase risk and others decrease it, which itself explains why the final answer had to come from an experimental trial rather than theoretical reasoning.
On the risk side: testosterone increases red blood cell production (erythrocytosis), raising hematocrit and blood viscosity — a mechanism we cover in detail in a separate entry on TRT and hematocrit. Thicker blood theoretically increases the load on the circulatory system and the risk of thromboembolic complications. Testosterone can also affect the lipid profile, though the direction and strength of that effect depend on the delivery form and the patient's baseline profile — covered in our related entry on TRT and cholesterol. On top of that comes a possible effect on fluid retention and, as TRAVERSE showed, on the risk of heart rhythm disturbances, including atrial fibrillation.
On the potential benefit side: low testosterone itself is linked, in observational studies, to a worse metabolic profile — higher visceral fat, worse insulin sensitivity, higher risk of metabolic syndrome and type 2 diabetes, and these are recognized, strong cardiovascular risk factors. Correcting a testosterone deficiency improves body composition, insulin sensitivity, and physical performance in some patients, which could theoretically protect the heart. It's precisely this two-directional pull — real mechanisms pointing both ways — that meant biology alone couldn't give a clear answer, and the dispute required empirical resolution, ideally in the form of a large, placebo-controlled randomized trial free of the systematic biases typical of observational data.
The key problem with observational studies, like the ones from 2013 and 2014, is so-called confounding by indication — men who get prescribed TRT systematically differ from those who don't, in terms of overall health, motivation to seek medical care, frequency of follow-up visits, and many other factors that are hard to fully standardize statistically. Randomization — randomly assigning participants to a testosterone or placebo group — is the only tool that eliminates this problem at its root, evenly distributing known and unknown confounders between groups.
2013 — Vigen et al., JAMA
A retrospective analysis of a veterans registry (over 8,700 men after coronary angiography) suggests a 29% increase in risk of a composite endpoint (death, heart attack, stroke) in men on testosterone therapy.
2014 — Finkle et al., PLOS ONE
An analysis of a large insurance database (over 55,000 men) shows an increased rate of non-fatal heart attacks within 90 days of starting TRT, especially in men 65 and older.
2014–2015 — FDA response
The agency issues a safety communication, narrows approved indications to documented hypogonadism, and adds a warning about possible cardiovascular risk to the labels of all testosterone products.
2014–2022 — years of scientific dispute
Both original analyses face sharp methodological criticism, including calls for correction from several scientific societies. Subsequent meta-analyses produce inconsistent results, without settling the debate.
2023 — TRAVERSE, Lincoff et al., NEJM
A large, placebo-controlled randomized trial, designed at the FDA's request specifically to settle this question, shows no increased MACE risk with TRT.
2025 — FDA label update
Based on TRAVERSE results, the agency removes the cardiovascular risk warning from testosterone labels, replacing it with an up-to-date summary of the evidence.
Evidence: strong — based on 4 studies in this database.
Benefits
Common myths
MythTRT definitely increases heart attack risk — large studies confirmed it.
FactThe studies this belief rested on (Vigen 2013, Finkle 2014) were observational and carried serious methodological limitations. The large, randomized TRAVERSE trial from 2023, designed specifically to test this, found no increased risk of major cardiovascular events.
MythSince TRAVERSE found no increased heart attack risk, testosterone is now fully safe for the heart in every respect.
FactThat's an oversimplification. TRAVERSE recorded a genuinely increased rate of atrial fibrillation, pulmonary embolism, and acute kidney injury in the treated group — signals that need to be factored into clinical practice, despite the absence of increased heart attack or stroke risk.
MythThe 2015 FDA warning is still in effect and means TRT is officially considered risky for the heart.
FactThe FDA updated testosterone product labels in 2025, removing the cardiovascular risk warning based on TRAVERSE results and incorporating current data into the product information.
Forms & variants
TRT and Your Heart — Does Testosterone Therapy Raise Heart Attack Risk? comes in several forms that differ in bioavailability and use case — the form you pick genuinely matters for how effective the supplementation is.
Observational studies (Vigen 2013, Finkle 2014)
Retrospective analyses of registries and insurance databases, susceptible to systematic biases like confounding by indication — unable to prove a causal relationship.
Best for: Historical context for the dispute; today regarded as hypothesis-generating rather than conclusive studies
TRAVERSE — a randomized, placebo-controlled trial
Designed specifically to settle the question of TRT's cardiovascular safety, with randomization eliminating the systematic biases typical of observational data.
Best for: The current gold standard of evidence on this question; the basis for current guidelines and FDA labeling
Practice
Frequently asked questions
The best available data — the large, randomized TRAVERSE trial from 2023 — found no increased risk of major cardiovascular events (including heart attack) in men on TRT compared with placebo, even in a population with existing or elevated cardiac risk. Earlier concerns were based on observational studies with significant methodological limitations.
From two large observational studies published in 2013 (Vigen et al., JAMA) and 2014 (Finkle et al., PLOS ONE), which suggested a link between TRT and increased cardiovascular event risk. They led to an FDA safety communication and warning in 2015, even though both analyses were retrospective and criticized for methodological problems.
Not in its original form. In 2025, based on TRAVERSE results, the FDA updated testosterone product labels, removing the cardiovascular risk warning and replacing it with a current summary of the trial data.
TRAVERSE was a large, randomized, placebo-controlled trial, commissioned by the FDA specifically to settle the question of TRT's cardiovascular safety. It included more than 5,200 men aged 45–80 with documented hypogonadism and existing or elevated cardiovascular risk, with an average treatment time of about 22 months and follow-up of about 33 months.
Because TRAVERSE, despite showing no increased heart attack or stroke risk, did show a genuinely increased rate of atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone-treated group. That's reason enough for standard cardiac assessment and hematocrit monitoring to remain a permanent part of safe therapy, not a formality.
TRAVERSE deliberately included men with existing or elevated cardiovascular risk — the group theoretically most vulnerable to potential harm — which strengthens the reassuring results' relevance to men with lower baseline risk too, though individual physician judgment always remains warranted.
Dosage & timing
Typical dose
Not applicable in the sense of drug dosing — what matters here is assessing cardiovascular risk before starting therapy and monitoring it throughout, regardless of the testosterone dose chosen.
Form
Baseline cardiac assessment (history, blood pressure, possibly an ECG if history warrants it), a complete blood count with hematocrit, a lipid profile — as part of TRT qualification and ongoing monitoring.
TRAVERSE included men with existing or elevated cardiovascular risk, so its results carry particular practical weight — they concern exactly the group the dispute was about.
Best times to take it
- Cardiovascular risk assessment before starting therapy, not during it
- Blood count checks (hematocrit) on the standard TRT monitoring schedule — usually after 3–4 months, then every 6–12 months
- An ad hoc cardiology consult if symptoms suggestive of a heart rhythm disturbance appear, regardless of the planned checkup schedule
What actually helps
Baseline cardiovascular risk assessment before TRT
Strong evidenceHistory taking for coronary artery disease, stroke, heart failure, and rhythm disturbances, blood pressure measurement, lipid profile assessment, and, where warranted, a cardiology consult — a standard part of qualification, regardless of the TRAVERSE results.
Monitoring hematocrit during therapy
Strong evidenceRegular blood count checks limit the risk of excessive erythrocytosis, which indirectly adds to cardiovascular load — the full schedule is covered in our related entry on TRT and hematocrit.
Vigilance for atrial fibrillation symptoms
Moderate evidenceHeart palpitations, an irregular rhythm, or sudden exertional shortness of breath in a patient on TRT should prompt a cardiology consult and possibly an ECG, given the signal detected in TRAVERSE — not as a reason to panic, but as warranted clinical vigilance.
Individualization for high-risk patients
Moderate evidenceIn men with a recent cardiovascular event or uncompensated heart disease, the decision to start TRT is made jointly with a cardiologist, despite the generally reassuring TRAVERSE results — the trial didn't include patients in an acute disease phase.
Safety
Side effects & contraindications
Possible side effects
Increased rate of atrial fibrillation in the testosterone-treated group in the TRAVERSE trial (3.5% vs. 2.4% in the placebo group)
Increased rate of non-fatal heart rhythm disturbances requiring intervention (5.2% vs. 3.0% in the placebo group)
Increased rate of pulmonary embolism in the treated group (0.9% vs. 0.5% in the placebo group)
Increased rate of acute kidney injury in the treated group (2.3% vs. 1.5% in the placebo group)
An indirect contribution from erythrocytosis (rise in hematocrit) to the theoretical risk of clotting complications — a mechanism covered in detail in a separate entry
Contraindications
A recent heart attack or stroke (most clinical protocols require a waiting period and stabilization before considering TRT)
Uncompensated, severe heart failure
Untreated, significant heart rhythm disturbances, especially with a history of atrial fibrillation — requires individual cardiology assessment before and during therapy
Uncorrected, significantly elevated baseline hematocrit (see the entry on TRT and hematocrit)
Active or recent venous thromboembolism without an explained and corrected cause
Interactions
Anticoagulant and antiplatelet drugs — require closer monitoring given the concurrent rise in hematocrit on TRT
Other arrhythmia risk factors (e.g. hyperthyroidism, electrolyte imbalances, excess caffeine or alcohol intake) can stack with the atrial fibrillation signal observed in TRAVERSE
Nephrotoxic drugs or dehydration — can additively increase the risk of acute kidney injury seen in the testosterone group in TRAVERSE
Supplements and drugs that raise hematocrit (e.g. unwarranted iron supplementation, EPO doping) — intensify the theoretical clotting risk independent of testosterone therapy itself
Is it worth taking?
Who it's for
- Men considering TRT who've heard about the FDA warning and want to know whether it's still current
- Patients already on testosterone therapy, concerned by years-old media coverage of heart attack risk
- People with existing cardiovascular risk factors who want to know the exact TRAVERSE data before talking to their doctor
- Doctors and patients looking for a current, evidence-based summary of this entire debate
Not for
- A recent heart attack or stroke (most clinical protocols require a waiting period and stabilization before considering TRT)
- Uncompensated, severe heart failure
- Untreated, significant heart rhythm disturbances, especially with a history of atrial fibrillation — requires individual cardiology assessment before and during therapy
- Uncorrected, significantly elevated baseline hematocrit (see the entry on TRT and hematocrit)
- Active or recent venous thromboembolism without an explained and corrected cause
Evidence
Worth knowing
Two observational studies from 2013 and 2014 (Vigen et al., Finkle et al.) launched a decade of concern over TRT's cardiovascular safety.
The FDA added a cardiovascular risk warning to testosterone labels in 2015.
TRAVERSE (2023) included more than 5,200 men with hypogonadism and existing or elevated cardiovascular risk — exactly the group the earlier concerns were about.
Primary result: 7.0% MACE events in the testosterone group vs. 7.3% in the placebo group — testosterone non-inferior to placebo.
Even so, TRAVERSE showed a higher rate of atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone-treated group.
The FDA removed the cardiovascular risk warning from testosterone labels in 2025, based on the TRAVERSE results.
Studies
Testosterone was non-inferior to placebo for the incidence of major cardiovascular events in men with hypogonadism and existing or elevated cardiovascular risk.
Lincoff AM et al. (TRAVERSE), New England Journal of Medicine, 2023
Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels
Early-stage evidenceVigen R, O'Donnell CI, Barón AE et al. · JAMA · 2013
A retrospective analysis of a veterans registry (over 8,700 men after coronary angiography) suggesting a roughly 29% increase in risk of a composite endpoint (death, heart attack, stroke) in men on TRT. An observational study, later heavily criticized for methodological flaws and comparison-group problems — one of the two sources that launched the 2015 FDA warning.
View studyIncreased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men
Early-stage evidenceFinkle WD, Greenland S, Ridgeway GK et al. · PLOS ONE · 2014
An analysis of a large insurance database (over 55,000 men) showing an increased rate of non-fatal heart attacks within 90 days of starting TRT, with an especially pronounced increase in men 65 and older. Like the Vigen study, observational and susceptible to systematic bias, but a significant factor in the FDA's decision to add a warning.
View studyCardiovascular Safety of Testosterone-Replacement Therapy
Strong evidenceLincoff AM, Bhasin S, Flevaris P et al. (TRAVERSE Study Investigators) · New England Journal of Medicine · 2023
A large, placebo-controlled randomized trial (over 5,200 men, 45–80 years, with hypogonadism and existing or elevated cardiovascular risk), commissioned by the FDA specifically to settle the question of TRT's cardiovascular safety. Testosterone was non-inferior to placebo for major cardiovascular events (MACE: 7.0% vs. 7.3%), while showing higher rates of atrial fibrillation (3.5% vs. 2.4%), pulmonary embolism (0.9% vs. 0.5%), and acute kidney injury (2.3% vs. 1.5%) in the treated group.
View studyFDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack and Stroke
Moderate evidenceU.S. Food and Drug Administration · FDA Drug Safety Communication · 2015
An official FDA safety communication from March 2015, narrowing approved testosterone indications to documented hypogonadism and adding a warning about possible increased heart attack and stroke risk — a decision based partly on the Vigen and Finkle studies, rescinded in 2025 following the TRAVERSE results.
View studySources & bibliography
- Vigen et al. 2013 — JAMA
- Finkle et al. 2014 — PLOS ONE
- Lincoff et al. 2023 — TRAVERSE, New England Journal of Medicine
- FDA — Testosterone Information (history of safety communications)
Citations are illustrative for this demo version and require full bibliographic verification by the editorial team before production publication.
Compare with similar entries
About the authors of this entry
Author
dr Piotr ZielińskiEndocrinologist
Piotr reviews content on hormones, metabolic health and supplement pharmacology.
131 publications on this site
Medical review
dr Anna KowalczykEditor-in-Chief, Molecular Biology
Anna oversees the editorial process and scientific review of every publication in the knowledge base. She previously researched autophagy and mitochondrial biology.
50 publications on this site
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Comments (2)
- KW
Kasia W. 2 weeks ago
Very clearly explained, especially the interactions section — I hadn't seen it laid out this well anywhere else.
- MT
Marek T. a month ago
Are you planning to update this with the newest study from this year? I saw an interesting meta-analysis.