Testosterone and atrial fibrillation: Why too much and too little can be harmful

It's like so many things in life: you just have to find the golden mean, the perfect measure. When it comes to testosterone, this is more than just a fact of life. A new review suggests that atrial fibrillation may be more common in men with both low and high testosterone levels.

Atrial fibrillation is the most common cardiac arrhythmia worldwide. The risk increases with increasing age; men are affected more often than women. For a long time, research focused primarily on low testosterone levels. Previous studies had shown that men with low values ​​were more likely to develop atrial fibrillation.

Researchers at the University of Kansas Medical Center and the Kansas City Veterans Affairs Medical Center have now summarized and classified previous research on testosterone and cardiac arrhythmias. Their results were published in the journal “Journal of the Endocrine Society”.

They considered, among other things, randomized trials, large observational studies, meta-analyses and laboratory studies. According to the researchers, the results increasingly draw a U-shaped curve in which the risk appears to increase at both ends of the testosterone distribution.

A 2017 study of more than 76,000 US veterans even found that men were less likely to develop atrial fibrillation when low testosterone levels were normalized with treatment. More recent research complicates the picture. Data from the UK Biobank suggested that not only very low but also high testosterone levels were associated with more atrial fibrillation.

In another analysis of 4,570 healthy older men, the risk in the two groups with the highest testosterone levels was almost twice as high as in men in the middle range. However, an increased risk at low values ​​could not be clearly demonstrated in this study. There is also evidence of a possible risk with testosterone replacement therapy.

In the large Traverse study of 5,246 men between the ages of 45 and 80, atrial fibrillation occurred in 3.5 percent of men who received testosterone gel. In the placebo group it was 2.4 percent. However, other studies could not clearly confirm this effect.

There is now a possible explanation for the question of why both extremes could be unfavorable. Low testosterone levels can disrupt processes that help heart muscle cells regulate calcium. This can create additional electrical impulses. High testosterone levels, in turn, affect certain potassium currents and shorten the electrical recovery phase of the heart muscle cells. This can promote circular electrical excitations that can trigger atrial fibrillation.

However, the data situation is not entirely clear. An evaluation of 106 placebo-controlled studies with a total of more than 15,000 men found no statistically clear increase in atrial fibrillation under testosterone therapy. Additionally, low testosterone is often associated with obesity, and obesity itself is a strong risk factor for atrial fibrillation. The authors of the new review therefore emphasize that the U-shaped relationship needs to be further investigated.

From the data so far, they still derive a possible favorable range: the risk of atrial fibrillation appears to be lowest at testosterone levels of around 350 to 550 nanograms per deciliter. However, this area was derived from observational data and has not yet been examined in a targeted clinical study.

According to the authors, for men with testosterone deficiency this means, above all, that treatment should aim at an individually appropriate value in the middle range instead of trying to achieve a maximum. Because values ​​in the upper normal range would not bring any additional benefit. What is more important is an individually tailored target value and regular monitoring - especially for older men or those with existing cardiovascular risks.