TRAVERSE trial testosterone results and what regulators did

The TRAVERSE trial testosterone results, published in the New England Journal of Medicine in June 2023, covered 5,246 men aged 45 to 80 with cardiovascular risk and confirmed low testosterone. Testosterone was non-inferior to placebo for major adverse cardiac events. The US Food and Drug Administration removed the cardiovascular boxed warning in February 2025. Canada has not followed.

Key takeaways

• TRAVERSE, New England Journal of Medicine, June 2023: 5,246 men aged 45 to 80 with two fasting testosterone levels below 300 ng/dL.
• Per the current US label, major adverse cardiac events occurred in 7 percent of men on testosterone versus 7.3 percent on placebo.
• The FDA’s class-wide labelling changes of 28 February 2025 removed the boxed warning language on increased cardiovascular risk and added the TRAVERSE results to all testosterone labels.
• Bhasin’s 2023 prostate substudy in JAMA Network Open found high-grade prostate cancer in 5 of 2,596 treated men (0.19 percent) versus 3 of 2,602 (0.12 percent), hazard ratio 1.62 (P = 0.51).
• Snyder’s 2024 fracture substudy found clinical fractures in 91 men (3.50 percent) on testosterone versus 64 (2.46 percent), hazard ratio 1.43 (95% CI 1.04 to 1.97).
• Health Canada has issued nothing on testosterone since 15 July 2014, and the Canadian monograph authorized 12 December 2025 still states that safety and efficacy for age-related hypogonadism are not established.

Who does this evidence apply to?

TRAVERSE enrolled men with confirmed low testosterone, and that is who its results describe. Entry required hypogonadal symptoms and two fasting testosterone levels below 300 ng/dL. Nothing in the trial speaks to men whose testosterone is normal.

The regulators say the same. Health Canada’s Information Update of 15 July 2014 advises against use for non-specific symptoms without laboratory confirmation of a low level, and its product monograph for oral testosterone undecanoate, authorized 12 December 2025, requires deficiency confirmed by two separate validated biochemical assays using morning testosterone. See our page on how low testosterone is diagnosed in Canada.

What was the TRAVERSE trial?

TRAVERSE was a randomized, placebo-controlled cardiovascular safety trial of testosterone replacement, published by Lincoff in the New England Journal of Medicine in June 2023. It enrolled 5,246 men aged 45 to 80 with existing cardiovascular disease or a high risk of it, hypogonadal symptoms, and two fasting testosterone levels below 300 ng/dL.

Men were randomized to a daily 1.62 percent testosterone gel or to placebo, and the primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. The population was selected for cardiovascular risk, which is where the earlier safety concern had been raised.

What did the TRAVERSE trial testosterone results show on cardiovascular risk?

Testosterone was non-inferior to placebo on the composite cardiovascular outcome. Per the current US label, major adverse cardiac events occurred in 7 percent of men on testosterone versus 7.3 percent on placebo.

That is the finding that changed the regulatory picture. It is not a claim that testosterone improves cardiovascular outcomes. Non-inferiority means the trial ruled out the harm it was designed to detect, in the population it enrolled, over the period it ran.

What did the TRAVERSE substudies find?

The trial produced a series of nested studies, and they do not all point the same way.

Fractures

Fractures were higher on testosterone, not lower. Snyder’s 2024 report in the New England Journal of Medicine, covering 5,204 men followed for a median of 3.19 years, found clinical fracture in 91 men (3.50 percent) on testosterone versus 64 (2.46 percent) on placebo, hazard ratio 1.43 (95% CI 1.04 to 1.97). Bone density does rise on treatment, as Snyder’s 2017 T-Trials bone study showed, but fracture prevention is not a reason to start. Those numbers are in our page on what testosterone therapy actually does.

Anemia

Anemia correction was one of the trial’s clearest benefits. Pencina’s 2023 report in JAMA Network Open, covering 5,204 men of whom 815 had anemia, found anemia corrected in a greater proportion of treated men at every time point, from 41.0 percent versus 27.5 percent at 6 months to 44.6 versus 39.2 at 48 months (p = 0.002). The abstract reports proportions rather than a single effect estimate.

Sexual function

Sexual activity improved, erectile function did not. Pencina’s 2024 report in the Journal of Clinical Endocrinology and Metabolism covered 1,161 men with low libido. The between-group difference in sexual activity was 0.49 acts per day (95% CI 0.19 to 0.79) at 6 months and 0.47 (95% CI 0.11 to 0.83) at 12 months, maintained at 24 months, with improvement in hypogonadal symptoms and sexual desire. Erectile function did not improve versus placebo.

Diabetes

Testosterone did not prevent progression to diabetes in this trial. Bhasin’s 2024 report in JAMA Internal Medicine covered 1,175 men with prediabetes and 3,880 with diabetes inside TRAVERSE, and progression did not differ between groups. The authors state that testosterone alone should not be used to prevent or treat diabetes. That sits against the T4DM trial, published in Lancet Diabetes and Endocrinology in 2021, which did show prevention in a different population. The two are compared in our page on testosterone, blood sugar and metabolic health.

Prostate safety

Prostate events were low and did not differ significantly between groups. Bhasin’s 2023 report in JAMA Network Open analyzed 5,204 men of mean age 63.3 years at 316 US trial sites. Over 14,304 person-years, high-grade prostate cancer (Gleason score 4 + 3 or higher) occurred in 5 of 2,596 men (0.19 percent) on testosterone versus 3 of 2,602 (0.12 percent) on placebo, hazard ratio 1.62 (95% CI 0.39 to 6.77, P = 0.51). Any prostate cancer, acute urinary retention, invasive prostate procedures, biopsy, new drug treatment for lower urinary tract symptoms and change in the International Prostate Symptom Score also did not differ. Prostate-specific antigen rose more on testosterone.

Who that result applies to matters. Men with a prostate-specific antigen above 3.0 ng/mL and an IPSS above 19 were excluded, and baseline mean PSA was 0.92 ng/mL with a mean IPSS of 7.1. The authors conclude that in men “carefully evaluated to exclude those at high risk of prostate cancer,” these events were low and did not differ significantly. On 18 June 2026 the FDA requested that the prostate cancer contraindication be narrowed to metastatic disease only, with continued monitoring rather than exclusion for benign prostatic hyperplasia.

The unfavourable signals

Atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often in the testosterone group. The trial authors state this and these appear in the US label, but the event counts are unknown from the sources used for this page. What follows from them is monitoring, covered in our page on monitoring on testosterone therapy in Canada.

Summary table of TRAVERSE findings

What did the FDA do with the TRAVERSE results?

It removed a boxed warning. On 28 February 2025 the FDA issued class-wide labelling changes for testosterone products: removal of the boxed warning language on increased cardiovascular risk; addition of the TRAVERSE results to all labels, namely that the trial found no increase in the risk of adverse cardiovascular outcomes in men using testosterone for hypogonadism; product-specific blood pressure information; and a new blood pressure warning for products that lacked one.

The same announcement stated that ambulatory blood pressure monitoring studies confirmed an increase in blood pressure with all testosterone products, class-wide. A US testosterone enanthate prescribing information revised in July 2025 shows the result: its boxed warning is now about blood pressure increases, and it reports a mean systolic increase of 1.0 mm Hg from baseline to 36 months, with ambulatory systolic and diastolic increases averaging 3.9 and 1.5 mm Hg at 12 weeks.

The June 2026 requests

On 18 June 2026 the US Department of Health and Human Services announced requested updates to testosterone therapy product labels. The FDA asked manufacturers to remove the limitation of use stating that safety and effectiveness in men with age-related hypogonadism have not been established, citing TRAVERSE and describing it as more than 5,200 men with no meaningful increase in the risk of major adverse cardiovascular events.

These are requests, not completed changes. The most recent US label verified for this page, revised in July 2025, still carries the age-related limitation.

What has Health Canada done since TRAVERSE?

Nothing. Health Canada has issued no new statement on testosterone since 15 July 2014, and there is no Canadian regulatory response to TRAVERSE, to the FDA’s February 2025 labelling change, or to the June 2026 requested US changes.

Its Summary Safety Review of 15 July 2014 reviewed 35 Canadian reports of cardiovascular problems received to 31 August 2013 and concluded that post-market studies suggested an increased risk of serious cardiovascular problems that may be linked to testosterone products. That is still the most recent Canadian safety communication.

Canadian labelling reflects that gap. The product monograph for oral testosterone undecanoate authorized 12 December 2025 states that safety and efficacy for age-related hypogonadism are not established, precisely the limitation the FDA asked US manufacturers to remove six months later. That monograph carries warnings on blood pressure increases and venous thromboembolism, and no boxed warning. The two jurisdictions now hold different positions on the same molecule, compared in full in our page on how the rules differ between Canada, the US, Europe and Australia.

Has anything independent confirmed TRAVERSE?

Yes, twice, from evidence bases that do not depend on the trial itself. Hudson’s 2022 meta-analysis in Lancet Healthy Longevity covered 35 studies and 5,601 participants. Cardiovascular events occurred in 7.5 percent on testosterone versus 7.2 percent on placebo, odds ratio 1.07 (95% CI 0.81 to 1.42), and deaths were 0.4 percent versus 0.8 percent, odds ratio 0.46 (95% CI 0.17 to 1.24). The authors state that long-term safety data beyond roughly one year of average exposure are lacking.

Corona’s 2024 review in Expert Opinion on Drug Safety covered 106 studies, 8,126 men treated and 7,310 on placebo, found no difference in major adverse cardiovascular events, and examined the atrial fibrillation signal raised by TRAVERSE.

What the evidence does not show

TRAVERSE did not show that testosterone protects the heart. Non-inferiority is the absence of the harm the trial was powered to detect, not a benefit.

It did not show fracture prevention. Clinical fractures were higher on testosterone, 91 (3.50 percent) versus 64 (2.46 percent), hazard ratio 1.43 (95% CI 1.04 to 1.97), in Snyder’s 2024 report. It did not show diabetes prevention either: Bhasin’s 2024 report found no difference in progression among 1,175 men with prediabetes and 3,880 with diabetes.

The prostate result is reassuring only for the men it studied, since a prostate-specific antigen above 3.0 ng/mL and an IPSS above 19 were exclusions.

It did not remove every safety question. Atrial fibrillation, acute kidney injury and pulmonary embolism were all higher on testosterone, and the FDA’s February 2025 review confirmed a class-wide blood pressure increase. Hudson’s 2022 analysis states that long-term safety data beyond roughly one year of average exposure are lacking, and none of this applies to men whose testosterone is normal.

Frequently asked questions

Did TRAVERSE prove testosterone is safe for the heart?

It showed non-inferiority to placebo for the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke in 5,246 men aged 45 to 80 who had or were at high risk of cardiovascular disease. Per the current US label, major adverse cardiac events occurred in 7 percent on testosterone versus 7.3 percent on placebo. Atrial fibrillation, acute kidney injury and pulmonary embolism were higher on testosterone.

Why did the FDA remove the boxed warning?

On 28 February 2025 the FDA issued class-wide labelling changes for testosterone products, removing the boxed warning language on increased cardiovascular risk and adding the TRAVERSE results to all testosterone labels, namely that the trial found no increase in the risk of adverse cardiovascular outcomes in men using testosterone for hypogonadism. The same review confirmed a class-wide increase in blood pressure and added blood pressure warnings.

Has Health Canada changed anything because of TRAVERSE?

No. Health Canada has issued nothing on testosterone since 15 July 2014, when it published a Summary Safety Review of 35 Canadian cardiovascular reports received to 31 August 2013 and an Information Update on the same day. There is no Canadian regulatory response to TRAVERSE, to the FDA’s February 2025 change, or to the June 2026 requested US changes.

Does the Canadian label say testosterone works for age-related low testosterone?

No. Health Canada’s product monograph for oral testosterone undecanoate, authorized 12 December 2025, states that safety and efficacy for age-related hypogonadism are not established. On 18 June 2026 the FDA requested that US manufacturers remove that same limitation of use, citing TRAVERSE. Canada has made no equivalent change, so the two labels currently differ on this point.

Did TRAVERSE find any benefits?

Yes, in nested substudies. Pencina’s 2023 report in JAMA Network Open found anemia corrected in 44.6 percent of treated men versus 39.2 percent on placebo at 48 months (p = 0.002) among 815 anemic men. Pencina’s 2024 report found a sexual activity difference of 0.49 acts per day (95% CI 0.19 to 0.79) at 6 months in 1,161 men with low libido, although erectile function did not improve.

Who was excluded from TRAVERSE?

The trial enrolled men aged 45 to 80 with hypogonadal symptoms and two fasting testosterone levels below 300 ng/dL, so men with normal testosterone were not studied. Bhasin’s 2023 prostate substudy in JAMA Network Open reports that men with a prostate-specific antigen above 3.0 ng/mL and an International Prostate Symptom Score above 19 were excluded. Speak with your doctor or pharmacist about whether any of this applies to you.

References

1. Lincoff AM, et al. 2023. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. PMID 37326322. DOI: https://doi.org/10.1056/NEJMoa2215025
2. Snyder PJ, et al. 2024. Fracture substudy of the TRAVERSE trial (full title unknown from the sources used for this page). New England Journal of Medicine. PMID 38231621. DOI: https://doi.org/10.1056/NEJMoa2308836
3. Pencina KM, et al. 2023. Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Network Open. PMID 37889486. DOI: https://doi.org/10.1001/jamanetworkopen.2023.40030
4. Pencina KM, et al. 2024. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. Journal of Clinical Endocrinology and Metabolism. PMID 37589949. DOI: https://doi.org/10.1210/clinem/dgad484
5. Bhasin S, et al. 2024. Diabetes substudy of the TRAVERSE trial (full title unknown from the sources used for this page). JAMA Internal Medicine. PMID 38315466. DOI: https://doi.org/10.1001/jamainternmed.2023.7862
6. Bhasin S, et al. 2023. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Network Open. PMID 38150256. DOI: https://doi.org/10.1001/jamanetworkopen.2023.48692
7. Hudson J, et al. 2022. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longevity. PMID 35711614. DOI: https://doi.org/10.1016/S2666-7568(22)00096-4
8. Corona G, et al. 2024. Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis. Expert Opinion on Drug Safety. PMID 38553429. DOI: https://doi.org/10.1080/14740338.2024.2337741
9. Snyder PJ, et al. 2017. Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial. JAMA Internal Medicine. PMID 28241231. DOI: https://doi.org/10.1001/jamainternmed.2016.9539
10. Wittert G, et al. 2021. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes and Endocrinology. PMID 33338415. DOI: https://doi.org/10.1016/S2213-8587(20)30367-3
11. Bhasin S, et al. 2018. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism. PMID 29562364. DOI: https://doi.org/10.1210/jc.2018-00229
12. United States Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. 28 February 2025. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products
13. United States Department of Health and Human Services. HHS Announces Requested Updates to Testosterone Therapy Product Labels. 18 June 2026. https://www.hhs.gov/press-room/fda-requests-updates-testosterone-therapy-labeling.html
14. United States Food and Drug Administration. Testosterone information. Last updated 23 June 2026. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/testosterone-information
15. United States Food and Drug Administration. Prescribing information, testosterone enanthate injection. Revised July 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209863s020lbl.pdf
16. Health Canada. Summary Safety Review, Testosterone Replacement Products, Cardiovascular Risk. 15 July 2014. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR00058
17. Health Canada. Information Update, Possible cardiovascular problems associated with testosterone products. 15 July 2014. https://recalls-rappels.canada.ca/en/alert-recall/information-update-possible-cardiovascular-problems-associated-testosterone-products
18. Health Canada. Product monograph, testosterone undecanoate oral capsules. Authorized 12 December 2025. https://pdf.hres.ca/dpd_pm/00082762.PDF
19. European Association of Urology. Guidelines on Sexual and Reproductive Health, male hypogonadism chapter, 2026 edition, limited update March 2026. https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-hypogonadism

This page is educational information, not medical advice. Testosterone is a prescription medication and a controlled substance in Canada. Talk to your doctor or pharmacist about your own situation.