Is it Time to Bring an End to Men’s Health Inequality?

America has just taken a major step forward in how it views testosterone replacement therapy (TRT), and it should be a wake-up call for the UK.
A landmark conversation between leading clinicians and the US Food and Drug Administration (FDA), underpinned by data from the TRAVERSE trial and other peer‑reviewed evidence, is reshaping the narrative around testosterone, cardiovascular risk, and male health more broadly.[1][2][3][4]

What TRAVERSE Really Showed

Mohit Khera, MD, MBA, MPH, professor of urology at Baylor College of Medicine and an investigator on the TRAVERSE trial has been central in communicating what this study actually found.
TRAVERSE is the largest randomized, double‑blind, placebo‑controlled non‑inferiority trial of testosterone therapy to date, enrolling 5,246 men aged 45–80 years with symptomatic hypogonadism and pre‑existing or high cardiovascular risk.[5][2][1]

Published in the New England Journal of Medicine in 2023, TRAVERSE demonstrated that testosterone therapy was non‑inferior to placebo for major adverse cardiovascular events (MACE: cardiovascular death, non‑fatal myocardial infarction, non‑fatal stroke).
Over a median follow‑up of around two years, a primary MACE occurred in 7.0% of men on testosterone versus 7.3% on placebo (hazard ratio 0.96; 95% CI 0.78–1.17; P<0.001 for non‑inferiority), directly addressing longstanding fears that TRT “causes heart attacks and strokes.”[6][2][1]

Testosterone: Not A Lifestyle Drug

Khera and others have been clear: testosterone is not a carcinogen, not an inherent cardiovascular risk factor, and not merely a lifestyle drug.
Decades of observational and interventional work show that untreated testosterone deficiency is associated with worse cardiometabolic health, increased all‑cause and cardiovascular mortality, and significant reductions in quality of life.[2][7][8][5]

Peer‑reviewed studies and guideline reviews report that low testosterone is linked with higher rates of type 2 diabetes, metabolic syndrome, obesity, frailty, osteoporosis, anaemia, erectile dysfunction, and depressive symptoms.
Conversely, when used in appropriately diagnosed hypogonadal men, TRT improves body composition, glycaemic control, bone mineral density, sexual function, mood and correction of anaemia, without increasing MACE in high‑risk populations in trials like TRAVERSE and recent meta‑analyses.[9][7][8][1]

Cardiovascular and Mortality Data: A Snapshot

• TRAVERSE: Non‑inferior cardiovascular safety vs placebo in high‑risk men with genuine hypogonadism.[1][2]
• Longitudinal cohorts: Low total and free testosterone associate with higher all‑cause and cardiovascular mortality, even after adjustment for traditional risk factors.[7][8]
• Observational: Effective, sustained TRT in hypogonadal men is associated with reductions in cardiovascular events and mortality compared with untreated or undertreated men, although confounding requires cautious interpretation.[9][7]

The FDA’s 2025 Label Change

In February 2025, the FDA issued class‑wide labelling changes for testosterone products, explicitly recommending removal of the boxed warning about increased risk of major adverse cardiovascular events.
The agency has now required that product labels incorporate the TRAVERSE findings and has shifted the focus toward more nuanced safety information, including product‑specific blood pressure warnings where ambulatory blood pressure monitoring (ABPM) studies show small increases in blood pressure.[3][10][4][5]

This represents a fundamental reframing: earlier safety communications in 2014–2015 had implied or suggested that TRT might independently increase risks of myocardial infarction, stroke, and death, leading to widespread caution or avoidance.
Post‑marketing trials and meta‑analyses have not confirmed a causal increase in MACE when TRT is prescribed for true hypogonadism, prompting this regulatory correction.[10][11][1][9]

Peer‑Reviewed Evidence Beyond TRAVERSE

TRAVERSE does not stand alone; it sits on top of a broader evidence base now difficult to ignore. Key strands include:[8][9]

• Randomised trials and pooled analyses showing no excess MACE with TRT in men with low testosterone, with some studies hinting at cardiometabolic benefit via improved fat mass, insulin resistance, and lipid profiles.[8][9]
• Meta‑analyses in high‑risk populations suggesting that TRT is not associated with increased cardiovascular events and may modestly improve certain risk markers when dosed to physiological levels and monitored correctly.[7][9]
• Data linking TRT to improvements in bone mineral density, reduced fracture risk surrogates, and correction of functional iron‑deficiency/anaemia, all of which are clinically meaningful in ageing men.[2][8]

At the same time, these studies highlight important caveats: TRT is not a panacea, is not indicated for age‑related “low‑normal” levels in otherwise well men, and must be accompanied by proper monitoring of haematocrit, prostate parameters, and cardiovascular risk factors.
It must be considered as a treatment option alongside addressing reversible causes and adjustment to lifestyle changes.[12][8]

Where This Leaves British and European Guidelines

In many respects, UK and European specialist societies have quietly been ahead of the curve.
The British Society for Sexual Medicine (BSSM) guidelines on adult male testosterone deficiency state that there is no consistent evidence that testosterone therapy, when used to treat true hypogonadism, increases cardiovascular risk; indeed, they argue that low testosterone itself should be considered a modifiable cardiovascular risk factor.[13][12][7]

BSSM, European Association of Urology (EAU), and European Society for Sexual Medicine (ESSM) guidance all emphasise:[13][8]

• Diagnosis based on symptoms plus repeatedly low testosterone (typically total testosterone <8 nmol/L, with a trial of therapy considered between 8–12 nmol/L when symptomatic).
• Comprehensive risk assessment and lifestyle optimisation alongside TRT.
• Routine monitoring of haematocrit, PSA, cardiovascular risk factors and treatment response, with dose adjustment or cessation if safety thresholds are breached.

By contrast, US regulators historically adopted a more restrictive position driven by earlier observational signals and concern about age‑related prescribing, which has only now been softened following TRAVERSE.[4][11]

Why the UK Now Needs Its Own “TRAVERSE Moment”

Despite relatively progressive UK and European guidelines, practice on the ground in the NHS and even in private care often lags far behind.
Many men are still denied investigation or treatment for textbook symptoms and biochemistry of hypogonadism, sometimes on the basis of outdated fears about prostate cancer or cardiovascular events that have been repeatedly challenged by contemporary evidence.[14][7][13]

The FDA’s move matters for the UK for three reasons:

1. It signals that one of the most conservative regulators has accepted that modern data do not support a blanket cardiovascular warning on TRT for appropriately selected men.[3][4]
2. It legitimises what BSSM and others have been saying for years: untreated low testosterone carries its own risks and deserves proactive, evidence‑based management.[7][13]
3. It raises an uncomfortable question: why are so many British men with clear hypogonadism still unable to access timely diagnosis and treatment, while American regulators are updating labels to reflect reassurance on cardiovascular safety?[13]

The Path Forward

For the UK, a similar joined‑up discussion is urgently needed—bringing together the MHRA, NICE, BSSM, Society for Endocrinology, primary care leaders and patient representatives.
This conversation should focus on aligning regulatory messaging, commissioning, and frontline practice with the current evidence:

Testosterone is a vital hormone across multiple organ systems; deficiency is harmful; and well‑indicated, well‑monitored TRT is not the cardiovascular villain it was once feared to be.

As men’s health outcomes continue to lag behind women’s across almost every major metric, failing to act on this body of evidence is no longer a neutral position — it is a choice to perpetuate inequality.[8][7]

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[1] Cardiovascular Safety of Testosterone-Replacement Therapy https://pubmed.ncbi.nlm.nih.gov/37326322/

[2] Making Sense of the TRAVERSE Trials https://www.androgensociety.org/learning-resources/traverse

[3] FDA removes cardiovascular warning from testosterone products https://www.advisory.com/daily-briefing/2025/03/11/around-the-nation

[4] FDA issues class-wide labeling changes for testosterone products https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products

[5] Testosterone and Cardiovascular Risk: TRAVERSE Trial and New ... https://grandroundsinurology.com/testosterone-and-cardiovascular-risk-traverse-trial-and-new-fda-label-change/

[6] Testosterone Therapy: TRAVERSE Study Insights & Myths https://1stoptimal.com/traverse-study-critique/

[7] Erectile dysfunction and testosterone deficiency as ... https://bssm.org.uk/wp-content/uploads/2023/02/ijcp13054-1.pdf

[8] Review Article https://bssm.org.uk/wp-content/uploads/2023/08/WJMH22-1027-4-Copy.pdf

[9] Cardiovascular safety of testosterone replacement therapy ... https://wchh.onlinelibrary.wiley.com/doi/10.1002/tre.967

[10] FDA Revises Testosterone Labeling: Removal of Boxed Warning Signals New Era for TRT https://www.carieboyd.com/news/fda-revises-testosterone-labeling/

[11] FDA cautions about using testosterone products for low testosterone ... https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-cautions-about-using-testosterone-products-low-testosterone-due

[12] Guidelines on Adult Testosterone Deficiency, With ... https://bssm.org.uk/wp-content/uploads/2023/02/guidelines-on-adult-testosterone-deficiency-with-statements-for-uk-practice.pdf

[13] The British Society for Sexual Medicine Guidelines on Male ... https://pmc.ncbi.nlm.nih.gov/articles/PMC10307648/

[14] Free Resources https://bssm.org.uk/free-resources/

[15] Safety of Testosterone-Replacement Therapy in Older Men https://www.ovid.com/journals/nejm/fulltext/00006024-202307130-00012~safety-of-testosterone-replacement-therapy-in-older-men

[16] NCT03518034 | A Study to Evaluate the Effect of ... https://www.clinicaltrials.gov/study/NCT03518034

[17] TRT and Heart Health: What's the Link? https://legerclinic.co.uk/blogs/testosterone-health-hub/trt-and-heart-health-what-s-the-link

[18] FDA Removes Black Box Warning on TRT: What You Need to Know https://quali-tmenshealth.com/fda-removes-black-box-warning-on-trt-what-you-need-to-know

[19] A practical guide on the assessment and management ... https://bssm.org.uk/wp-content/uploads/2023/02/BSSM-Practical-Guide-High-Res-single-pp-view-final.pdf

[20] FDA issues labeling changes for testosterone products following ... https://www.urologytimes.com/view/fda-issues-label-changes-for-testosterone-products-following-traverse-post-market-studies

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