In men, the risk of atrial fibrillation — a common heart rhythm disorder — may increase with both very low and very high testosterone levels. This is the conclusion reached by the authors of a review of studies published in the Journal of the Endocrine Society. At the same time, the researchers emphasize that evidence on the effects of testosterone replacement therapy (TRT) on the risk of arrhythmia remains conflicting.
Previous studies have mainly linked low testosterone levels to an increased risk of atrial fibrillation, particularly among older men. However, more recent research suggests that the risk may also be associated with excessive levels of the hormone.
One of the largest studies was the TRAVERSE trial, published in 2023. Atrial fibrillation occurred more frequently among men receiving testosterone gel than among those receiving a placebo. At the same time, a 2024 meta-analysis of 106 randomized studies found no statistically significant increase in arrhythmia risk associated with TRT. Observational studies of patients have also produced mixed results.
Particularly interesting findings came from the UK Biobank and ASPREE studies. They point to a possible U-shaped relationship: the risk of atrial fibrillation may be higher at both low and high testosterone concentrations, while it may be lower at intermediate levels. In the ASPREE study, older men with the highest testosterone levels had nearly twice the risk of atrial fibrillation compared with participants with intermediate levels.
Based on the available evidence, the authors suggested that the lowest risk may occur at total testosterone levels of approximately 12–19 nmol/L. However, this is only an observed association and should not be interpreted as an established safe range or medical recommendation.
The researchers suggest that the mechanism may involve testosterone’s effects on the electrical activity of heart cells. Very low hormone levels may disrupt calcium regulation, while high levels may alter the function of potassium channels. Both processes could potentially contribute to the development of arrhythmias.
Thus, the review does not establish that testosterone replacement therapy itself necessarily causes atrial fibrillation. However, it suggests that the relationship between testosterone levels and cardiovascular health may be more complex than previously thought.
The authors say further research is needed to determine how different forms of TRT and individual factors — including age, obesity, diabetes, hypertension and sleep apnea — affect the risk of arrhythmia.
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