By Colleen Power Kupka, MSN, FNP-C
In August 2026, Healio’s Endocrine Today, a medical news site that a lot of physicians read, ran this headline: “Off-label testosterone use may raise cardiovascular risk for men.” The article was about a study by Dr. Hatim Kerniss and his colleagues at University Hospital Frankfurt in Germany, published in the journal eBioMedicine.
If you’re a man on testosterone, or your husband is, I know how a headline like that lands. In my opinion, this was a scary headline for a study that wasn’t even a randomized controlled trial, and it shouldn’t have been released that way. It’s time for these scary headlines to go away. So let’s talk about what this study actually found, and just as important, what it didn’t.
What Did They Do?
First things first. This was not a randomized controlled trial. It was a database study. The researchers went into TriNetX, a large global database of electronic health records, and looked back at records that already existed.
They pulled men between 30 and 75 who had been prescribed testosterone and split them into two groups. One group had low testosterone or symptoms of it documented in their charts. The other group didn’t. The researchers did try to make the groups comparable by matching them on things recorded in the charts. The second group had more heart attacks, strokes, and deaths.
Every Man in This Study Was on Testosterone
This is the part that bothers me most. There was no group of men who weren’t on testosterone. None. They compared men on testosterone to other men on testosterone. So how can you say testosterone caused the problem? You can’t. All this tells us is that the two groups of men were different.
And even with matching, there’s a good chance they were, because you can only match on what’s in the chart. In a records database, “no low testosterone” may just mean a lab or symptom was never entered into the chart. So who’s in that group? It could be men with incomplete records, men getting testosterone from another clinic, or men using high doses for bodybuilding without anyone checking their labs. The study doesn’t tell us. It didn’t report doses, testosterone levels, or blood counts, and that’s exactly what I would need to know.
Something else jumped out at me. The men in that second group had almost double the risk of dying from anything, but their risk of heart attack was only slightly higher. That makes me ask: what was really driving all those deaths? The study doesn’t answer that, and I think it’s a big question left open.
Database Study vs. Randomized Trial: Why It Matters
A database study looks backward at records that already exist. Nobody was assigned to treatment, so the groups can be very different in ways that never made it into the chart. It can find a link, but it can’t prove cause.
A randomized controlled trial (RCT) looks forward. People are assigned to treatment or placebo by chance, so both groups start out the same. If one group has more heart attacks, the treatment is the only real difference.
That’s why database studies raise questions, and randomized trials answer them. When they disagree, I go with the randomized trial.
So What Does the Best Evidence Say?
We actually have the answer. TRAVERSE was a randomized, placebo-controlled trial, the gold standard, published in the New England Journal of Medicine in 2023. It was designed to answer whether testosterone is safe for the heart in men who truly have low testosterone.
They enrolled 5,246 men between 45 and 80 with low testosterone. And these weren’t healthy young guys. Every one of them already had heart disease or a high risk for it. These are the men we’d worry about most. Half got testosterone and half got placebo.
The results? Heart attacks, strokes, and cardiovascular deaths: 7.0% on testosterone and 7.3% on placebo. Basically the same.
TRAVERSE is the study that led the FDA to remove the cardiovascular black box warning from all testosterone products in 2025. And in June 2026, the FDA went even further and asked manufacturers to remove the old limitation on treating age-related low testosterone.
So the FDA already looked at the best evidence we have and took that warning off. A look back at health records doesn’t change that.
What I Watch For
I’m not going to pretend TRAVERSE was all good news. You deserve the whole picture. Atrial fibrillation, an irregular heart rhythm, happened in 3.5% of men on testosterone compared with 2.4% on placebo. AFib becomes more common as we age, and these men were 45 to 80 with heart disease or high heart risk, so some of it is expected. But there was still a small increase in the testosterone group. Blood clots in the lungs were also uncommon, 0.9% compared with 0.5%. Small numbers, but real. Testosterone can also raise blood pressure.
That’s why testosterone is not a free-for-all. Before starting, your provider should be asking about any history of blood clots or heart rhythm problems. Once you’re on it, your blood pressure and blood count should be checked, and your heart health should be part of the conversation.
Where I Agree With Dr. Kerniss, and Where I Don’t
Dr. Kerniss said testosterone shouldn’t be given for aging-related symptoms like fatigue without an adequate diagnostic evaluation. I agree 100% that men need a proper evaluation.
But fatigue is not a throwaway complaint. It’s one of the classic symptoms of low testosterone, along with low libido, erectile problems, low mood, and losing muscle and strength.
The problem isn’t treating fatigue. The problem is treating fatigue without asking why. Fatigue can also come from your thyroid, sleep apnea, anemia, depression, and other conditions. A good evaluation looks at the whole person: symptoms, labs, and health history.
My philosophy has always been this: symptoms lead, and labs are the safety rails. When a man is exhausted, has other symptoms of low testosterone, and his evaluation supports it, that fatigue deserves to be taken seriously and treated.
My Bottom Line
Looking back at health records can raise questions, but it can’t answer them. This study is a good reminder to prescribe carefully. It is not proof that testosterone hurts your heart. The best evidence we have, a large randomized trial, found that for men who truly need it, testosterone did not increase the risk of heart attack or stroke.
Honestly, I’m tired of seeing fear created by observational studies when we already have TRAVERSE. We have randomized data on this. Men deserve headlines that reflect the best evidence, not the scariest.
Please don’t let a headline scare you away from getting help. If you have symptoms of low testosterone, find a provider who will listen to you, look at the whole picture, and monitor you carefully.
This article is for educational purposes only and is not medical advice. Talk with your healthcare provider about whether testosterone therapy is right for you.
References
- Lincoff AM, et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). New England Journal of Medicine. 2023;389:107-117.
- Kerniss H, et al. eBioMedicine. 2026. doi:10.1016/j.ebiom.2026.106373
- Healio / Endocrine Today. “Off-label testosterone use may raise cardiovascular risk for men.” August 4, 2026.
- U.S. Food and Drug Administration. “FDA issues class-wide labeling changes for testosterone products.” February 28, 2025.
- U.S. Department of Health and Human Services. “HHS Announces Requested Updates to Testosterone Therapy Product Labels.” June 18, 2026.