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Testosterone levels that are too low or too high may increase the risk of atrial fibrillation, raising questions about how replacement therapy should be administered. The study’s findings were published in the Journal of the Endocrine Society.
Millions of middle-aged and older men receive testosterone replacement therapy, but its effects on heart rhythm deserve closer attention. A new review suggests they may need to consider this further.
Men with unusually low or unusually high testosterone levels appear to have an increased risk of developing atrial fibrillation, a heart rhythm disorder that is much more serious than initially thought.
The review combined data from population studies, clinical trials, and several recent laboratory studies to explore how testosterone levels actually relate to the risk of developing atrial fibrillation.
Testosterone therapy has become one of the most commonly prescribed hormonal treatments in older men. It’s often used for fatigue, decreased libido, or muscle atrophy, which is why questions about its long-term cardiac safety are so intriguing.
Both extremes are dangerous.
“Testosterone replacement therapy is widely prescribed to middle-aged and older men, and atrial fibrillation is a heart rhythm disorder that increases the risk of stroke and often requires lifelong blood thinning medications,” said study co-author Rajat S. Baruah of the Kansas City Veterans Affairs Medical Center. “Our paper reviewed the available evidence on whether testosterone therapy is safe or unsafe for atrial fibrillation and examined the range of testosterone levels associated with the lowest risk.” Both low and high testosterone levels appear to increase the risk of atrial fibrillation through different biological mechanisms, meaning that dose and target level matter.”
According to Baruah, the review argues that treatment should be individualized and monitored individually. After analyzing often conflicting data, the researchers arrived at a U-shaped pattern. Men with low testosterone levels had an increased risk, as did men with high testosterone levels.
The lowest risk was located right in the middle of the normal range, not at either extreme. This U-shaped curve differs markedly from the older, simplistic assumption that doctors only need to monitor low testosterone levels.
It’s not just a matter of conjecture, but also because the U-shaped pattern isn’t based solely on one type of evidence. Large-scale population studies tracking the association of testosterone levels with cardiovascular disease point in the same direction.
Laboratory research published since 2025 shows that low and high testosterone levels affect heart cells through two completely different mechanisms, all independently pointing in the same direction.
This is worth noting. This means that this pattern isn’t just a statistical coincidence. There’s a real biological story unfolding at the cellular level, and the fact that two independent lines of evidence converge on the same principle makes it difficult to dismiss this finding as a statistical fluke.
The authors note that for men who truly require testosterone therapy, the goal shouldn’t be to raise testosterone levels to the upper limit of normal. A mid-range value of approximately 350 to 550 ng/dL total testosterone should be aimed for, using slow-release preparations and closely monitoring patients over the long term.
However, this specific range of values is based on observational data rather than a prospective study, so it is more of a reasonable starting point than a definitive figure, and future research may well refine it.
The personalization of this approach means that in cases where sex hormone-binding globulin levels show abnormalities, the calculated free testosterone level should be used rather than the total testosterone level, as total testosterone levels alone can be misleading in such cases.
This also means preferring stable, sustained-release formulations over short-acting ones in men who already have Increased risk of cardiovascular disease or arrhythmia. This means avoiding sudden changes, which are typically caused by rapid-acting injections.
Physicians should also assess risks before initiating treatment, paying particular attention to obesity, sleep apnea, hypertension, and alcohol abuse, if present. Finally, heart rate, hematocrit, blood pressure, and renal and hepatic function should be monitored throughout treatment.
The authors clearly state what this article is and is not. This is a review article, synthesizing existing literature, not a formal meta-analysis using pooled statistical data. Given how confusing the available evidence remains, this is worth keeping in mind.
The recommendations appear reasonable given the currently available data, but prospective studies in this area are still awaited to determine the ideal range with sufficient confidence.
Such studies would allow men’s health to be tracked over time using systematic cardiac monitoring, rather than relying on the retrospective and observational data available today.
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