- Healthy, older men with higher concentrations of testosterone were more likely to develop atrial fibrillation, according to a new study.
- The findings follow a landmark 2023 trial that found that men using testosterone-replacement therapy had a higher incidence of atrial fibrillation.
- Maintaining testosterone in a healthy, normal range appears to mitigate atrial fibrillation risk.
Higher natural testosterone levels are associated with an increased risk of atrial fibrillation (AFib).
The findings, published April 29 in The Lancet, substantiate prior research that identified a higher incidence of AFib among men who used testosterone-replacement therapy (TRT). In 2023, researchers published a landmark study, known as the TRAVERSE trial, that found that men with pre-existing or high risk of cardiovascular disease using TRT were not at increased risk of death from cardiovascular disease. However, it did find that men prescribed TRT did have slightly higher rates of AFib.
Using that research as a jumping-off point, the authors of The Lancet study wanted to investigate whether they could identify an association between testosterone and AFib in men who were not prescribed TRT, using only natural testosterone levels.
“Amongst 4,570 initially healthy older aged men aged 70 years or older, those with testosterone concentrations at the higher end of the clinical normal range had nearly double the risk of developing AFib compared to men in the middle of the range,” Cammie Tran, MPH, a researcher at the Monash University School of Public Health in Australia, and First Author of the study, told Healthline.
The risk factors for AFib
Tran and her team utilized data from the ASPREE clinical trial, a long-term study that looks at the effects of aspirin on health in older adults for their study. They included 4,570 males with an average age of 74 years old with no history of cardiovascular disease (including AFib). Participants had their circulating testosterone concentrations measured at baseline. During an average 3-5 year follow-up period, researchers observed that 286 participants, or around 6%, developed AF.
They found that men who developed AFib had higher baseline testosterone levels compared to those that did not. The average testosterone concentration for the men who developed AFib was 17 nmol/L compared to 15.7 nmol/L. They also tended to be current or former tobacco smokers and had a higher baseline BMI. However, the association between testosterone and AFib persisted after controlling for these factors.
“Male sex has been recognized as a risk factor for AFib for a long time, but it’s been hard to determine whether that was due to the effect of testosterone directly, or just other risk factors that are more common in men. This study found that higher testosterone levels conferred a higher risk for [AFib] even when other clinical risk factors like age, BMI, smoking, and alcohol use were accounted for. This suggests a direct role for testosterone,” M. Ben Shoemaker, MD, the Director of Vanderbilt University’s Atrial Fibrillation Precision Medicine Program, told Healthline. Shoemaker wasn’t affiliated with the research.
The ideal testosterone level
Another important finding of the study was that the association between testosterone concentrations and AFib was not linear. That means what they found isn’t as simple as: higher testosterone equals a higher risk of atrial fibrillation.
Men in the high-normal of testosterone concentration did have higher risk of AFib, but so did men below the normal range.
“This study suggests that testosterone levels need to be ‘just right,’” said Shoemaker.
Prior related studies have come to similar conclusions.
A 2017 study published in the Journal of the American Heart Association found that men with low testosterone had a higher incidence of AFib compared to men within a normal range. But, when their testosterone levels were normalized through TRT, the prevalence of AFib dropped.
“Men with higher testosterone concentrations had a higher risk of atrial fibrillation, but there was no reduction of risk in men with lower testosterone. Our results would suggest that being within the mid-range of the clinical normal range would be best for lower risk of [AFib],” said Tran.
Testosterone and TRT: what to know
Despite the findings, the mechanism for why testosterone outside of normal ranges is associated with AFib is still not known.
“Originally, the focus was on testosterone’s role in regulating gene expression- a process that slowly increases the risk of [AFib] over time. Now, it’s recognized that testosterone can directly bind to receptors in the heart that regulate its electrical activity, and those changes promote AFib,” said Shoemaker.
Maintaining testosterone in a healthy range is therefore important due to AFib risk, but overall health as well.
Low testosterone, also called low T and testosterone deficiency, is defined as a concentration of less than 300 ng/dl, according to the American Urology Association. Testosterone production and circulating concentration typically decrease with age.
Signs and symptoms of low T include:
- Low sex drive
- Erectile dysfunction
- Decreased muscle mass
- Increased body fat
- Low energy
- Smaller testicle and penis size
For individuals with low T, a doctor may prescribe TRT, or testosterone replacement therapy, to increase the circulating concentration of testosterone.
TRT is also frequently used off-label for various non-medical issues like gaining muscle mass, losing weight, and boosting sexual performance. It is also popularly believed to have “anti-aging” properties. However, the use of TRT for these purposes may be illegal and without scientific merit.
Risks of high testosterone from TRT include:
- Acne
- High blood pressure
- Difficulty urinating
- Shrinking of testicles
- Fluid retention
“Recreational or off-label use of testosterone needs to be strongly discouraged. There are risks of harm, including heart-related complications in androgen abusers. Testosterone should only be prescribed to men with medical conditions necessitating this treatment, with appropriate medical supervision and monitoring,” said Tran.
The bottom line
In healthy older men, abnormal testosterone levels were associated with a greater risk of developing AFib, according to a new study.
The findings follow the findings of the 2023 TRAVERSE trial that identified men using testosterone-replacement therapy as having higher incidence of AFib, but not other cardiovascular disease risks.
Experts say that maintaining testosterone concentrations in a normal range — neither too high nor too low — is optimal to minimize AFib risk.
