WASHINGTON—Men with either low or high testosterone levels may face a higher risk of atrial fibrillation, highlighting the need for personalized testosterone treatment, according to a review of existing evidence on testosterone and heart health published today in the Journal of the Endocrine Society.
Co-author Rajat S. Barua, M.D., Ph.D., of Kansas City Veterans Affairs Medical Center in Kansas City, Mo., said, "Testosterone replacement therapy is widely prescribed for middle-aged and older men, and atrial fibrillation is a heart rhythm disorder that increases stroke risk and often requires lifelong blood-thinning medication. Our paper reviewed existing evidence on whether testosterone therapy is safe or unsafe in relation to atrial fibrillation and the range of testosterone levels associated with the lowest risk. Both too little and too much testosterone appear to raise the risk of atrial fibrillation, through separate biological mechanisms, which means the dose and the target level matter. What the review argues is that treatment should be individualized and monitored."
The researchers concluded from the available and conflicting evidence that the relationship between testosterone and atrial fibrillation (AF) appears to follow a U-shaped pattern: men with low testosterone and men with high testosterone both show a higher risk of atrial fibrillation, while the risk appears to be lowest in the middle of the normal range.
Barua explains that this pattern has support from two directions: large population studies and, since 2025, laboratory work showing that low and high testosterone disturb heart cells through two different mechanisms.
For men who need testosterone replacement therapy, the authors state the goal for clinicians should be aiming to restore testosterone to the middle of the normal range (approximately 350–550 ng/dL total testosterone) rather than pushing it to the high end, using steady-release formulations and structured monitoring. The therapeutic range of total testosterone, 350–550 ng/dL, is inferred from observational data and has not been tested prospectively yet.
The authors expand on ways to personalize treatment and monitor symptoms for men who need testosterone therapy:
- Use calculated free testosterone when Sex Hormone-Binding Globulin (SHBG) is abnormal.
- Prefer stable-pharmacokinetic formulations over short-acting formulations in men with elevated cardiovascular or arrhythmic risk.
- Maintain normal hematocrit as the principal dose-limiting safety constraint.
- Risk-stratify before initiation and address obesity, sleep apnea, hypertension, and alcohol use.
- Monitor rhythm, hematocrit, blood pressure, and renal and hepatic function.
The authors note that the review is a narrative summarizing existing literature rather than a meta-analysis, so its conclusions are interpretive.
Other authors are Anand Reddy Maligireddy of the University of Kansas Medical Center in Kansas City, Kan., and Shumedha T. Barua of Kansas City VA Medical Center.
The review received no external funding.
"Association of Testosterone and Testosterone Replacement Therapy with Atrial Fibrillation: An Updated Review" was published online.
