Testosterone replacement and the heart
Does testosterone replacement therapy increase cardiovascular risk?
A decade-long question, recently answered
In 2014 the FDA warned of reported strokes, heart attacks and deaths in men taking testosterone, and in 2015 required labelling changes urging caution.5 The question of whether replacing testosterone damages the heart then hung over the field for nearly ten years, unresolved, while prescriptions climbed.
It has now been answered about as well as this kind of question gets answered. The answer is no — and getting there requires being careful about what "no" covers.
What the definitive trial found
The FDA's 2014 advisory committee did something unusual: it required the industry to run a trial. That trial was TRAVERSE, and it reported in 2023.1
TRAVERSE — 5,246 men, mean follow-up 33 months1
HR 0.96 (0.78–1.17)
A 2024 meta-analysis pooling 30 randomized trials and 11,502 patients reached the same place across every major outcome.2
Pooled across 30 RCTs — testosterone vs placebo2
Noninferior is not the same as safe. TRAVERSE was designed to rule out an increase in major cardiac events, and it did. It was not designed to show benefit, and it did not show one.
And within the same trial, three things did occur more often on testosterone: atrial fibrillation, acute kidney injury, and pulmonary embolism.1 A clean primary endpoint and a set of secondary signals can coexist. Both are the result.
What the FDA actually did in February 2025
This was widely reported as "FDA removes testosterone heart warning." That happened. Two other things happened on the same day and are largely missing from the coverage.5
Boxed Warning language about increased risk of adverse cardiovascular outcomes — for all testosterone products.
The TRAVERSE results, to every product label.
A new warning about increased blood pressure, for products that did not already carry one. Postmarket ambulatory blood pressure studies "confirmed an increase in blood pressure with use of all testosterone products, class-wide."
The "Limitation of Use" language for age-related hypogonadism. Testosterone remains approved "solely for use in men who lack or have low testosterone levels in conjunction with an associated medical condition."
Read those four rows together and the shape is clear. One warning came off. Another went on. And the restriction that matters most for how testosterone is actually prescribed — that low testosterone from ageing alone is not an approved indication — was left exactly where it was.
"The FDA cleared testosterone" and "the FDA removed one cardiovascular warning while adding a blood-pressure warning and keeping the age-related limitation" are different sentences. Only the second is what happened.
What it does for symptoms — including the one it's sold on
Safety is one question; benefit is another. The Testosterone Trials assigned 790 men aged 65 or older, with testosterone below 275 ng/dL and symptoms, to testosterone gel or placebo for a year.3 The design deliberately split the outcomes people care about into separate trials.
The Testosterone Trials — 790 men over 65, one year3
P<0.001
The Vitality Trial is the one worth pausing on. Testosterone is marketed overwhelmingly on energy — tiredness, drive, feeling flat. A trial designed specifically to measure that, in exactly the population most likely to be prescribed it, found no significant benefit.3
The walking result carries a similar lesson. In the Physical Function Trial the difference was not significant; it became significant only when men from all three trials were pooled (20.5% vs 12.6%, P=0.003).3 A result that appears only after widening the sample is weaker than one that survives in the trial built to test it.
The authors also note, with unusual directness, that "the number of participants was too few to draw conclusions about the risks of testosterone treatment."3
Two different drugs sharing one name
Everything above concerns replacement — restoring a deficient man to a normal range. That is not what most people picture when they hear testosterone, and the distinction is the single most useful thing on this page.
Transdermal gel, daily
Population: T < 300 ng/dL
with symptoms
Restores a deficient man to the normal male range. This is what TRAVERSE and the Testosterone Trials studied, and what the FDA has approved.15
Injection
Population: normal men
with normal levels
Pushes a healthy man far above the normal range. This is what the classic anabolic literature studied, and it is not an approved use of the drug.4
The landmark trial of the second is worth knowing precisely, because it settles a question people still argue about. In 1996, 43 normal men were randomised to four groups — placebo or 600 mg testosterone enanthate weekly, each with or without strength training, for ten weeks.4
Bhasin et al. 1996 — testosterone without any exercise, vs placebo without exercise4
The men who took testosterone and did no exercise at all gained more muscle and strength than the men who took placebo and did no exercise. That is the finding, and it has never been seriously disputed.
Note what this does not tell you. It is one 43-man trial at roughly six times a replacement dose, run for ten weeks, in men whose testosterone was already normal. It establishes that supraphysiologic testosterone is anabolic. It says nothing about the safety of doing that, which TRAVERSE did not study either — TRAVERSE studied replacement, in deficient men, under medical supervision.
The cardiovascular reassurance on this page belongs to the left-hand column. It does not transfer to the right.
Four claims, four answers
The last three sit at Emerging because each rests on a single landmark trial rather than a replicated, pooled body of work — our scale requires two independent groups before Moderate. For the anabolic claim in particular this understates a finding almost nobody disputes; we grade what the pooled record supports, and note where that produces a mark lower than the field's own confidence.
Safety and unknowns
-
Adverse events reported
In TRAVERSE, higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism on testosterone.1 Postmarket ambulatory studies confirmed increased blood pressure class-wide across all testosterone products, prompting a new FDA warning.5 The 2024 pooled analysis found no significant difference in major cardiovascular outcomes or mortality.2
-
Longest human exposure studied
Mean treatment duration 21.7 months with mean follow-up 33.0 months in TRAVERSE.1 That is among the best long-term safety records of anything on this site — and it is still under three years, in men who typically take it indefinitely.
-
Known interactions and at-risk groups
The blood-pressure effect is class-wide and relevant to anyone with hypertension.5 The atrial fibrillation and pulmonary embolism signals matter most for men with existing arrhythmia or clotting risk. TRAVERSE enrolled men who already had or were at high risk of cardiovascular disease — so its reassurance applies to a higher-risk group than average, which strengthens rather than weakens it.
-
Regulatory status
Approved and prescription-only, "solely for use in men who lack or have low testosterone levels in conjunction with an associated medical condition."5 Low testosterone due to ageing alone remains outside the approved indication. Testosterone is a Schedule III controlled substance in the United States, and is prohibited in tested sport.
-
What has not been characterized
Exposure beyond about three years. Cardiovascular safety at supraphysiologic doses — no trial has studied that and none is likely to. Whether men with normal testosterone benefit at all; the trials enrolled deficient men by design. And the mechanism behind the atrial fibrillation, kidney and embolism signals, which TRAVERSE's authors described as unexpected.
How this was graded
Evidence strength — Strong, criteria checked
This is a Strong · Not supported of the most useful kind: a specific harm was alleged, a purpose-built trial was demanded by a regulator, it was run, and the allegation did not hold. The scale is not saying testosterone is harmless — it is saying the cardiovascular claim that dominated a decade of coverage was tested properly and was not borne out. The safety flag alongside carries what the trial did find.
Bottom line
Testosterone replacement does not increase heart attacks, strokes or cardiovascular death in men with diagnosed low testosterone. A 5,246-man trial the FDA demanded and a pooled analysis of 30 trials in 11,502 patients agree, and the FDA removed the boxed warning in February 2025.
On the same day it added a class-wide blood-pressure warning and kept the rule that ageing alone is not an approved reason to prescribe it. And TRAVERSE itself found more atrial fibrillation, kidney injury and pulmonary embolism in the men taking it.
What it does for symptoms is narrower than the marketing: better sexual function, slightly better mood, and — in the trial built to measure exactly this — no significant improvement in vitality. Meanwhile the anabolic results everyone quotes come from six times a replacement dose in men who were never deficient, a use no safety trial has ever examined.
Sources
- Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular safety of testosterone-replacement therapy. New England Journal of Medicine. 2023;389(2):107–117. TRAVERSE, NCT03518034; funded by AbbVie and others. PMID 37326322
- Jaiswal V, Sawhney A, Nebuwa C, Borra V, Deb N, Halder A, et al. Association between testosterone replacement therapy and cardiovascular outcomes: a meta-analysis of 30 randomized controlled trials. Progress in Cardiovascular Diseases. 2024;85:45–53. PMID 38589271
- Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. New England Journal of Medicine. 2016;374(7):611–624. The Testosterone Trials, NCT00799617. PMID 26886521
- Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. New England Journal of Medicine. 1996;335(1):1–7. PMID 8637535
- US Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. 28 February 2025. fda.gov
