TRT Heart Safety After TRAVERSE: What the FDA Changed
The FDA dropped testosterone's cardiovascular boxed warning in February 2025. That decision reset how men think about TRT heart safety — and it answered a far narrower question than the headlines suggested.
TRT heart safety is the question that kept a generation of men off testosterone therapy — and in February 2025 the FDA answered part of it. Since 2015, testosterone products sold in the United States carried label language warning about cardiovascular risk. That language is now gone, removed on the strength of a single trial: TRAVERSE, which randomized 5,246 men with low testosterone and either established heart disease or a high risk of developing it [1]. I have men in clinic every week who read the headline and arrive convinced the argument is closed. It isn’t closed — it’s narrower than that. TRAVERSE answered one question very well, left several open, and turned up two findings that never reached the news at all. What follows is what the trial showed, what the FDA actually changed, and what I check before and after I start a man on testosterone when his heart is already the concern. For the wider picture, see our Sexual Health Hub.
Key Takeaways
- TRAVERSE found no increase in cardiovascular death, heart attack or stroke over a mean 33 months of follow-up — but only in men with two confirmed testosterone levels below 300 ng/dL (10.4 nmol/L) who already carried high cardiac risk.
- The FDA removed the cardiovascular language from the boxed warning on 28 February 2025 and added a class-wide blood pressure warning in the same action.
- The same trial recorded more atrial fibrillation, pulmonary embolism, acute kidney injury and clinical fractures in the testosterone arm than in the placebo arm.
- Hematocrit is the number that predicts trouble: men who became polycythemic on testosterone had roughly 35% higher odds of a cardiovascular or clotting event in their first year of treatment.
What TRAVERSE Actually Tested — and Who Was in the Trial
TRAVERSE enrolled men aged 45 to 80 who had two fasting testosterone measurements below 300 ng/dL (10.4 nmol/L), at least one symptom of testosterone deficiency, and either existing cardiovascular disease or a high risk of it. Half received a daily 1.62% transdermal testosterone gel, titrated to hold levels between 350 and 750 ng/dL. Half received placebo gel [1].
The primary endpoint was the first occurrence of cardiovascular death, nonfatal heart attack or nonfatal stroke. It happened in 182 men (7.0%) on testosterone and 190 men (7.3%) on placebo — a hazard ratio of 0.96, with a confidence interval running from 0.78 to 1.17. Mean treatment lasted 21.7 months and mean follow-up ran 33 months.
Two design details change how you should read that result. First, this was a noninferiority trial, not a superiority trial. It was built to show testosterone is not worse than placebo, and that is exactly what it showed. Nothing in TRAVERSE says testosterone protects your heart. When a clinic markets it that way, they are reading a conclusion the trial never drew.
Second, every man in the trial used gel. No intramuscular cypionate, no long-acting undecanoate injections, no pellets, no compounded preparations. Injectable testosterone produces higher peak levels and, historically, the largest rises in hemoglobin and hematocrit of any modality. Applying a gel trial’s safety profile to a weekly injection is an assumption, not a finding — and it is the single most common overreach I see in patient-facing coverage. If you are still working out whether treatment is warranted in the first place, start with how low testosterone actually presents after 40 and what I tell patients before starting testosterone.
What the FDA Changed in February 2025 — and What It Left Alone
On 28 February 2025 the FDA notified manufacturers of class-wide labeling changes covering every approved form of testosterone — oral capsules, gels, patches, buccal systems and injections [2]. Four things happened at once, and only one of them was good news.
| Label element | Status after 28 February 2025 |
|---|---|
| Boxed warning language on adverse cardiovascular outcomes | Removed |
| TRAVERSE trial results | Added to every testosterone product |
| Blood pressure warning | Added class-wide |
| Limitation of use for age-related low testosterone | Retained unchanged |
Read the bottom row again, because it is the one the marketing skips. The FDA did not approve testosterone for age-related decline. The limitation-of-use language stayed exactly where it was. A man of 52 whose level has drifted from 620 to 430 ng/dL over fifteen years is still, in regulatory terms, outside the indication — regardless of what an online questionnaire tells him.
The second thing worth being precise about: the agency removed the cardiovascular language from the boxed warning, not the box. Topical products still carry boxed warning language about secondary exposure, and the AUA has long advised counseling every gel and cream user about transferring testosterone to a partner or child through skin contact [5]. Plenty of headlines reported that the boxed warning was deleted. It wasn’t.
Prescribing responded to the news the way you would expect. US testosterone prescribing prevalence reached 1.57% of men aged 50 to 64 in 2025, past its early-2010s peak, with every age group over 30 exceeding its own prior high [8]. More men on treatment means more men who need the monitoring done properly.
The TRT Heart Checklist: Which Blood Tests to Get Before You Start and Every Six Months After
Enter your email below to receive Dr. Khalid’s complete Low Testosterone: Testing & Treatment Guide as a free, printable PDF.
The TRAVERSE Findings That Didn’t Make the Headlines
The trial’s own authors reported a higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group [1]. These were not the primary endpoint and they were not powered to prove causation, which is precisely why they should be treated as signals rather than dismissed as noise. Atrial fibrillation and pulmonary embolism are both plausible downstream consequences of a thicker circulation, and the mechanism is not hypothetical.
Then there is the fracture subtrial, published a year later. Testosterone raises bone density, so the expectation was fewer fractures. The opposite appeared: after a median 3.19 years, a clinical fracture occurred in 91 of 2,601 men on testosterone (3.50%) versus 64 of 2,603 on placebo (2.46%), hazard ratio 1.43 [3]. Nobody has a settled explanation. The leading hypothesis is behavioral — men who feel stronger do more, and doing more is how you break a wrist.
The prostate substudy was genuinely reassuring, with a caveat. High-grade prostate cancer occurred in 5 of 2,596 testosterone-treated men and 3 of 2,602 on placebo — no significant difference, and no difference in urinary retention, biopsy rates or prostate surgery either. But men with a PSA above 3.0 ng/mL were excluded at enrollment, and PSA rose more in the testosterone group than in the placebo group [4]. That result applies to men screened before starting, not to men who skipped the screening.
In My Practice
A man in his late fifties came in with a two-day history of a swollen, aching left calf. He had been on testosterone for twenty-two months, prescribed after a single afternoon blood draw by an online service, with a repeat prescription arriving every ninety days. His hematocrit that afternoon was 57%. It had never been rechecked after the day he started — not once in nearly two years. He was not harmed by testosterone. He was harmed by a supply chain with no follow-up in it.
In almost every testosterone complication I have managed, the failure was in monitoring rather than in the drug itself.
TRT Heart Safety in Practice: Blood Pressure, Hematocrit and Monitoring
Blood pressure: small on average, concentrated in the wrong men
The FDA’s blood pressure warning came out of ambulatory monitoring studies, and the averages sound trivial. In one 155-man study of an oral testosterone undecanoate, mean 24-hour systolic pressure rose 1.7 mmHg at day 120 [7]. That is nothing.
The average hides the finding that matters. Among men already taking antihypertensive medication, systolic pressure rose 3.4 mmHg. Among men taking none, it rose 0.7 mmHg. The pressure increase concentrates in exactly the group least able to absorb it. If you already treat hypertension, buy a home monitor, take a baseline week of readings before your first dose, and repeat that week at three months. If those numbers move, the answer is usually to fix the pressure rather than abandon the testosterone — start with the lifestyle changes that genuinely move blood pressure, and if you want a sense of your baseline arterial risk before any of this, run our vascular age calculator.
Hematocrit: the number that actually predicts events
Testosterone stimulates red cell production. Push it far enough and blood becomes measurably more viscous, which is a clotting problem rather than a hormone problem. In an analysis of a 74-million-patient database, men who developed polycythemia on testosterone had a 5.15% rate of major adverse cardiovascular or venous thromboembolic events in their first year, against 3.87% in matched men whose hematocrit stayed normal — odds ratio 1.35 [6]. Notably, in the same study men on testosterone without polycythemia showed no excess risk compared with untreated men.
That is the practical version of TRT heart safety. The AUA position is straightforward: measure hemoglobin and hematocrit before offering treatment, investigate a baseline hematocrit above 50% before starting anything, and treat a hematocrit reaching 54% on therapy as a trigger for dose reduction or temporary discontinuation [5].
What to ask for, and when
- Before starting: two early-morning total testosterone levels drawn on separate days at the same laboratory, hemoglobin and hematocrit, a PSA if you are over 40, and a week of home blood pressure readings.
- If you have had a heart attack, stroke or revascularization: the AUA advises against commencing testosterone for three to six months after a cardiovascular event. Ask your cardiologist to confirm you are outside that window before your urology appointment.
- At three months: repeat testosterone level to confirm you are in range, repeat hematocrit, repeat the home blood pressure week.
- Then every six to twelve months: testosterone, hematocrit and PSA. If your clinic does not schedule these, that is the signal to change clinic.
- At three to six months, if levels normalized but symptoms did not: the guideline directs a discussion about stopping. Testosterone that fixes a number without fixing the complaint is not treating anything.
One more thing worth naming. Erection quality is often the reason a man asks about testosterone in the first place, and it is also one of the earliest reliable signals of arterial disease. If that is your route into this conversation, read why erection changes are frequently the first vascular warning before you decide the problem is hormonal.
Stop and Be Seen the Same Day
If you are on testosterone and any of the following happens, hold the next dose and get assessed immediately — do not wait for your next scheduled review:
- Sudden breathlessness, or sharp chest pain that worsens when you breathe in — go to the emergency room, this can be a pulmonary embolism.
- Pain, swelling, warmth or redness in one calf — emergency room the same day for a deep vein thrombosis assessment.
- A new irregular, fluttering or racing pulse — request an ECG this week to check for atrial fibrillation.
- Chest pressure or tightness brought on by exertion and relieved by rest — this needs cardiac assessment, not a testosterone dose adjustment.
And if you started testosterone in the last three months and nobody has rechecked your hematocrit, book that blood test this week regardless of how well you feel.
Frequently Asked Questions
Does TRT heart safety look the same for injections as it does for gel?
We do not know, and anyone who tells you otherwise is extrapolating. Every man in TRAVERSE used a 1.62% transdermal gel titrated to a target range. Injectable testosterone produces higher peak levels and larger rises in hemoglobin and hematocrit than transdermal delivery, and hematocrit is the variable most closely tied to clotting events. The gel data are reassuring for gel. They are an assumption for everything else.
If the boxed warning is gone, can I start TRT just because my level is low for my age?
No. The FDA kept the limitation-of-use language for age-related low testosterone in the same action that removed the cardiovascular warning. A diagnosis still requires two early-morning total testosterone levels below 300 ng/dL on separate days, combined with symptoms or signs. If you want to check whether your symptoms fit the pattern before booking bloods, work through our low testosterone symptom quiz and take the result with you.
How soon after a heart attack or stent can I start testosterone?
The AUA advises against commencing testosterone therapy for three to six months following a cardiovascular event. That window exists because the post-event period is when your cardiac medications, blood pressure and rhythm are still being stabilized, and adding a drug that nudges hematocrit and blood pressure into that situation makes any deterioration harder to attribute. Ask your cardiologist to confirm in writing that you are stable before your urology appointment.
Does testosterone raise my prostate cancer risk if I already have heart disease?
The TRAVERSE prostate substudy found no significant difference in high-grade prostate cancer between testosterone and placebo — five cases against three across more than 5,000 men. But that trial excluded anyone with a PSA above 3.0 ng/mL at entry, and PSA rose more in the treated group. The reassurance applies to men screened before starting. We cover the full evidence in the prostate cancer and testosterone question.
What hematocrit number should make me stop TRT?
A hematocrit reaching 54% on treatment warrants intervention — a dose reduction, a change of formulation, or a temporary stop until it falls. A hematocrit above 50% before you start should be investigated before any testosterone is prescribed, because something else may be driving it. Men who become polycythemic on testosterone carry measurably higher odds of a cardiovascular or clotting event in their first year of therapy.
References
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. PubMed
- US Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. 28 February 2025. FDA
- Snyder PJ, Bauer DC, Ellenberg SS, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. N Engl J Med. 2024;390(3):203-211. PubMed
- Bhasin S, Travison TG, Pencina KM, et al. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(12):e2348692. PubMed
- Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018;200(2):423-432. Reviewed and validity confirmed 2024. AUA
- Ory J, Nackeeran S, Balaji NC, et al. Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. J Urol. 2022;207(6):1295-1301. PubMed
- White WB, Bernstein JS, Rittmaster R, Dhingra O. Effects of the oral testosterone undecanoate Kyzatrex on ambulatory blood pressure in hypogonadal men. J Clin Hypertens. 2021;23(7):1420-1430. PubMed
- Epic Research. After Nearly a Decade-Long Decrease, Testosterone Prescribing Rates Rising Again. 2026. Epic Research
Dr. Muhammad Khalid
MBBS · FCPS (Urology) · MCPS (Gen. Surgery) · CHPE · CRSM · IMC #539472
Specialist urologist with 11+ years of clinical experience across tertiary teaching hospitals. Trained at Lady Reading Hospital and Khyber Teaching Hospital, Peshawar. Author of 5 peer-reviewed international publications in Cureus, WJSA, and AJBS. Procedural expertise: URS, PCNL, RIRS, TURP, TURBT, and major open urological surgery. Full profile →
This article is for educational purposes only and does not constitute medical advice. Always consult your physician or urologist for diagnosis and treatment decisions specific to your condition.
