Testosterone levels linked to U-shaped atrial fibrillation risk

A review published in the Journal of the Endocrine Society suggests atrial fibrillation risk may follow a U-shaped relationship with testosterone, increasing at both low and high levels, though evidence on replacement therapy remains mixed. The review analyzed clinical trials, observational studies, and genetic data, finding conflicting results. A 2023 trial showed higher AF rates with testosterone gel, while a 2024 meta-analysis found no significant increase. Observational studies supported a non-linear association, with risk nearly doubled in older men with high testosterone. Researchers proposed AF risk may be lowest at total serum testosterone levels of approximately 350 to 550 ng/dL, though this has not been prospectively validated. Mechanistic data suggest different pathways at low and high concentrations, and researchers called for prospective studies to clarify treatment targets.