7.0% vs 7.3%major cardiac events in TRAVERSE, testosterone gel against placebo
Safety · Hormones
Is testosterone replacement safe? What the trial and FDA label report
The biggest safety trial found no rise in major heart events for men with diagnosed low testosterone. The label that carries its results also lists higher clot, rhythm, kidney and fracture rates, and says safety in age-related low testosterone is not established.
On 2 November 2026, the AndroGel 1.62% label reported major adverse cardiac events in 7.0% of men on testosterone gel and 7.3% on placebo in the TRAVERSE trial. The same label lists higher rates of clots, atrial fibrillation, kidney injury and fractures on the gel, and says safety in age-related low testosterone is not established.
Source: the AndroGel 1.62% label on DailyMed (version 130, effective 22 October 2025), the TRAVERSE abstract on PubMed, and FDA's 28 February 2025 labeling page, read 2 November 2026.
The short version
7.0%on testosterone gelmajor cardiac events in TRAVERSE
7.3%on placebothe same events, the same trial
Higherother events on the gelclots, atrial fibrillation, kidney injury, fractures
Not setage-related low Tthe label says safety and efficacy are not established
Testosterone safety: claims against the labelwhat gets said, and what the record shows, read 2 November 2026
They sayFDA dropped the heart warning, so TRT is basically harmless now.
Not that simple
The 2025 change removed boxed-warning language on cardiovascular outcomes after TRAVERSE, and added a blood pressure warning. The label also lists more clots, atrial fibrillation and kidney injury on the gel than on placebo. See the receipt
They sayLow T from getting older is exactly what it is approved for.
Not cleared
The label says safety and efficacy in age-related hypogonadism have not been established. FDA kept that limitation of use in 2025. See the receipt
They sayIt will not touch your fertility.
A risk flag
The label says spermatogenesis may be suppressed and that reduced fertility is observed in some men on replacement therapy, with an impact that may be irreversible. See the receipt
What does this page read, and what does it leave out?
The AndroGel 1.62% label is the main document read here, sections 1 to 9: the boxed warning, indications, contraindications, warnings, adverse reactions and the abuse section.[1] It is one product's label, the gel that TRAVERSE tested, so injection, oral and patch labels were not read.
The TRAVERSE paper's abstract was read on PubMed, and FDA's 28 February 2025 labeling announcement was read in full.[2][3] The full paper was not read. For what FDA changed and how deep the trial record is, see the testosterone trial-record guide.
What did the TRAVERSE trial find?
TRAVERSE was a randomized, double-blind, placebo-controlled trial of testosterone gel in men 45 to 80 with symptoms of hypogonadism, two low fasting levels, and existing or high risk of cardiovascular disease.[2] The journal abstract counts 5,246 men enrolled, the label's analysis counts 5,198, and the trial is registered as NCT03518034.[1][4]
Death from cardiovascular causes, nonfatal heart attack or nonfatal stroke, first event, in men 45 to 80 with existing or high risk of cardiovascular disease. Hazard ratio 0.96, 95% confidence interval 0.78 to 1.17, meeting the trial's noninferiority margin. Mean treatment 21.7 months.Read the reasoning
Treatment lasted 21.7 months on average with 33 months of follow-up, and the label notes about 61% of men stopped the gel or placebo before the end.[1] The journal abstract adds that atrial fibrillation, acute kidney injury and pulmonary embolism were higher on testosterone.
Percent of men with each event, as the AndroGel 1.62% label reports TRAVERSE in sections 5.3 and 6.1. The label calls the clot difference "numerically higher"; the trial was built to test heart events, so these are not its primary result.
Venous clots: 1.7% on the gel against 1.2% on placebo, including deep vein clots 0.6% against 0.5% and lung clots 0.9% against 0.5%.[1]
Atrial fibrillation 3.5% against 2.4%, acute kidney injury 2.3% against 1.5%, bone fracture 3.5% against 2.5%, and arrhythmias needing intervention 5.2% against 3.3%.
The men studied averaged 63 years, mean body mass index 35, and mostly had diabetes, high blood pressure or high cholesterol, so they are not a young, lean group.
What does the label say about blood pressure?
FDA announced on 28 February 2025 that ambulatory blood pressure studies confirmed an increase in blood pressure with all testosterone products, and that labels would add a warning where one was missing.[3] The AndroGel label puts it in numbers.[1]
Mean change in systolic blood pressure from the label's sections 5.5 and 6.1: a 16-week ambulatory monitoring study (169 men with usable recordings, 72 on blood pressure medicine) and the TRAVERSE difference at 36 months. The label says increases can add cardiovascular risk over time.
Mean 24-hour systolic and diastolic pressure rose 1.9 and 1.3 mm Hg after 16 weeks, and 3.0 and 2.2 mm Hg in men already on blood pressure medicine.
In TRAVERSE, systolic pressure rose 1.0 mm Hg on the gel and fell 0.5 mm Hg on placebo by 36 months, a 1.5 mm Hg gap.
The label says increases can add cardiovascular risk over time, advises periodic measurement, and does not recommend the gel for uncontrolled hypertension.
What else does the label list?
The label's own trial of 234 men on the gel against 40 on placebo for 182 days found a raised PSA in 11.1% of men on the gel and none on placebo.[1] Mood swings, high blood pressure, raised hemoglobin or hematocrit and contact dermatitis each appeared in about 2 to 3% on the gel and none on placebo.
Table 4 of the label: 234 men on the gel against 40 on placebo for 182 days, and every listed reaction was 0% on placebo. The placebo group was small, so read the gap as a signal, not a rate.
The gel is contraindicated in men with breast cancer or known or suspected prostate cancer, and the label says men on androgens may be at increased risk of prostate cancer and should be evaluated before and during treatment.
Rising hematocrit can call for lowering or stopping treatment, because more red blood cells may raise the risk of clots.
Spermatogenesis may be suppressed, and the label says reduced fertility is observed in some men on replacement therapy and that the impact may be irreversible.
Post-marketing reports include heart attack, stroke, depression, hostility, sleep apnea and priapism, with the usual caveat that frequency and cause cannot always be reliably estimated.
Who is it for, and who should stay away?
The label covers replacement for adult men with a deficiency or absence of testosterone from primary or hypogonadotropic hypogonadism, and states that safety and efficacy in age-related hypogonadism have not been established.[1] FDA kept that limitation of use in 2025.[3]
The boxed warning is about secondary exposure: virilization has been reported in children who touched unwashed or unclothed application sites.
The gel is contraindicated in women who are pregnant and is not indicated for women or anyone under 18.
Testosterone is a Schedule III controlled substance. The label says it is abused, typically at higher doses and with other anabolic steroids, and lists serious heart and psychiatric reactions in people who abuse them.
Questions the label raises
1. Were two morning levels measured and low before anything was prescribed, and which condition is the diagnosis?
2. Blood pressure, hematocrit and PSA: how often will they be checked, and what happens if one rises?
3. Any history of clots, heart rhythm trouble, kidney disease, sleep apnea or prostate problems?
4. Planning a child? The label says reduced fertility may be irreversible. Ask first.
5. Anything else you take for training or looks: say so. The label links abuse with serious heart and mood events.
How much research looks at the side effects?
PubMed holds 767 papers on testosterone replacement in hypogonadism that mention adverse or side effects, cardiovascular events or risk, prostate cancer, polycythemia, erythrocytosis or venous thromboembolism, which is 36 percent of the 2,144 papers in the trial-record guide.[5] Of the 767, 40 are typed as randomized controlled trials[6] and 32 as reviews or meta-analyses.
PubMed papers whose title or abstract mention testosterone replacement, hypogonadism and a harm word, counted 2 November 2026. A word match shows where the research is, not how often anything happens.
A word match includes papers that mention a harm only to rule it out, and it says nothing about how often anything happens.
It shows that the harms have been studied beyond TRAVERSE, and that this page has not read that research.
TRAVERSE answers the first box for one gel in one kind of patient. The last two are where a prescriber earns the fee.
How should you use this page?
If you are asking whether it is safeSafer than feared on heart events, with real flagsOne large trial found no rise in major heart events in diagnosed men, and the label still lists clots, rhythm, kidney, blood pressure, prostate and fertility cautions. Weighing them is a prescriber's job.
If you are young, or low-normal and curiousOutside what the trial testedTRAVERSE enrolled men 45 to 80 with diagnosed low levels and heart risk. It says nothing about healthy younger men, and the label's fertility warning matters most to them.
If a seller says FDA cleared the heart riskRead the label insteadThe 2025 change is real and narrow. The same label added a blood pressure warning and still limits use in age-related low testosterone.
How this page was built
Method
The AndroGel 1.62% label was downloaded from DailyMed's structured product label service on 2 November 2026 and sections 1 to 9 were read in full, as was FDA's announcement. Every rate is quoted from the label, except the enrollment, treatment duration, hazard ratio and atrial fibrillation, kidney and embolism statement, which come from the PubMed abstract of the TRAVERSE paper. The label's dose, titration and application figures are left out on purpose, because this is not a dosing page.
Limits: one product's label, no injection, oral or patch labels, the TRAVERSE full paper not read, and no independent literature read. The side-effect count is a word match and measures depth of record only (our grading rules are on the methodology page, and the evidence ladder shows how other topics compare). Nothing here is medical advice.
The exact query
Testosterone replacement side effects: ("testosterone replacement"[tiab] OR "testosterone therapy"[tiab] OR "testosterone treatment"[tiab]) AND (hypogonadism[tiab] OR "low testosterone"[tiab]) AND (adverse[tiab] OR "side effect*"[tiab] OR "cardiovascular event*"[tiab] OR "cardiovascular risk"[tiab] OR "prostate cancer"[tiab] OR polycythemia[tiab] OR erythrocytosis[tiab] OR "venous thromboembolism"[tiab])
References
abcdefg DailyMed (National Library of Medicine). AndroGel 1.62% (testosterone gel) label, ASCEND Therapeutics US, version 130, effective 22 October 2025. Sections 1 to 9 were read. dailymed.nlm.nih.gov, read 2 November 2026.
ab Lincoff AM, Bhasin S, et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). N Engl J Med 2023;389:107-117. Abstract read; the full paper was not. pubmed.ncbi.nlm.nih.gov, read 2 November 2026.
abc FDA. FDA issues class-wide labeling changes for testosterone products (content current as of 28 February 2025). fda.gov, read 2 November 2026.
↑ ClinicalTrials.gov record NCT03518034, the TRAVERSE trial registration. clinicaltrials.gov, link checked 2 November 2026.
↑ PubMed search for testosterone replacement in hypogonadism narrowed to papers that mention adverse or side effects, cardiovascular events or risk, prostate cancer, polycythemia, erythrocytosis or venous thromboembolism in the title or abstract; the query is printed in the method section. pubmed.ncbi.nlm.nih.gov, read 2 November 2026.
↑ National Library of Medicine. MeSH publication type: Randomized Controlled Trial. ncbi.nlm.nih.gov.
FAQ
Is testosterone replacement therapy safe?
The AndroGel label does not say safe or unsafe. In the TRAVERSE trial, major cardiac events were 7.0% on testosterone gel and 7.3% on placebo in men 45 to 80 with diagnosed low testosterone and heart risk, and the label also lists higher clot, atrial fibrillation, kidney and fracture rates and a blood pressure warning. A prescriber weighs those against your tests and history.
Does testosterone replacement cause heart attacks?
In TRAVERSE, major adverse cardiac events (cardiovascular death, nonfatal heart attack or nonfatal stroke) were 7.0% on testosterone gel and 7.3% on placebo, which met the trial's noninferiority test. After it, FDA said it was removing boxed-warning language on adverse cardiovascular outcomes from all testosterone products.
Does testosterone replacement raise blood pressure?
Yes. FDA said in February 2025 that blood pressure studies confirmed an increase with all testosterone products. The AndroGel label reports a mean rise of 1.9 mm Hg systolic after 16 weeks, and 3.0 in men already on blood pressure medicine.
Can testosterone replacement affect fertility?
The label says spermatogenesis may be suppressed, that reduced fertility is observed in some men on replacement therapy, and that the impact may be irreversible. Anyone planning children should raise this with a prescriber first.
Is testosterone approved for low testosterone from aging?
The label says safety and efficacy in age-related hypogonadism have not been established, and FDA kept that limitation of use in its 2025 labeling changes. The approved use is replacement in men with a deficiency from a recognized hypogonadism.
Bottom line
One large trial found no rise in major heart events for diagnosed men, and the label that reports it still lists clots, rhythm and kidney events, a blood pressure rise, prostate and fertility cautions, and a limit on age-related use. Hold any claim that testosterone is "cleared" or "harmless" up against that wording, then take the specifics to a prescriber.
How do I cite this page?
Cite the page and the date its figures were read. Every count here is a count of records matching a published query on the day it was read, so it can move; the method box on this page prints the query so you can re-run it.
APA
Whitepill editorial desk. (2026, November 2). Is testosterone replacement safe? What the trial and FDA label report. Whitepill. https://whitepill.dev/articles/is-testosterone-replacement-safe-what-the-fda-label-reports
BibTeX
@online{whitepill_is_testosterone_replacement_safe, author = {{Whitepill editorial desk}}, title = {Is testosterone replacement safe? What the trial and FDA label report}, year = {2026}, month = nov, url = {https://whitepill.dev/articles/is-testosterone-replacement-safe-what-the-fda-label-reports}, note = {Last modified 2026-11-02}
}
Published 2 November 2026. Last modified 2 November 2026. Where a figure rests on secondary reporting, the page says so; do not present that as a primary source.
What has changed on this page?
new Published. Rates are quoted from the AndroGel 1.62% label on DailyMed (version 130, effective 22 October 2025) and the TRAVERSE abstract on PubMed, read on 2 November 2026.