A narrative review published in the Journal of the Endocrine Society examined available evidence on the relationship between testosterone levels, testosterone replacement therapy, and risk of atrial fibrillation (AF) in men. The review assessed large observational studies and more recent laboratory work to determine whether low or high testosterone, or exogenous testosterone treatment, is associated with changes in AF risk. The authors stress clinical implications for individualized treatment and monitoring when prescribing testosterone replacement therapy (TRT).
The central conclusion from the review is that the association between total testosterone and AF appears to follow a U-shaped pattern. Men with low total testosterone and men with high total testosterone both show higher observed rates of atrial fibrillation, while those with testosterone concentrations in the middle of the normal range have the lowest apparent risk. The review cites an inferred therapeutic target for men requiring TRT: restoring total testosterone to the mid-normal range rather than elevating levels to the high end. The authors report an approximate mid-normal total testosterone interval of 350–550 ng/dL derived from observational data; they note this range has not been prospectively validated.
Support for the U-shaped pattern is described as coming from two complementary sources. Large population-based observational studies identify associations between both low and high testosterone and increased AF risk. Since 2025, laboratory investigations have provided mechanistic insights, suggesting that low and high testosterone disturb cardiac myocytes through distinct biological pathways. The review integrates these epidemiologic and experimental findings to propose that different mechanisms likely underlie the increased arrhythmic risk at the low and high ends of the testosterone spectrum.
Based on the review, the authors recommend an individualized approach to TRT in men who meet criteria for therapy. Key points include:
Aim to restore total testosterone into the mid-normal range (approximately 350–550 ng/dL) rather than pushing to the high end of the reference interval. This recommendation is drawn from observational associations and has not been tested in prospective trials.
Use calculated free testosterone for assessment when Sex Hormone-Binding Globulin (SHBG) is abnormal, to better estimate bioavailable hormone.
Prefer steady-release or stable-pharmacokinetic formulations over short-acting preparations in men at elevated cardiovascular or arrhythmic risk, to avoid wide fluctuations in serum testosterone.
Consider normal hematocrit as the principal safety constraint for dose adjustments; hematocrit elevation remains a dose-limiting adverse effect of TRT.
Perform pre-treatment risk stratification and address modifiable contributors to AF risk, including obesity, obstructive sleep apnea, hypertension, and excess alcohol use.
The review lists specific monitoring measures recommended for men on TRT:
Rhythm surveillance to detect new or worsening atrial fibrillation.
Periodic hematocrit checks to detect erythrocytosis, with hematocrit used as the main parameter to limit dosing when required.
Blood pressure monitoring, and assessment of renal and hepatic function during therapy.
These measures are intended to reduce the likelihood that TRT will contribute to increased cardiovascular or arrhythmic risk and to allow timely intervention if adverse effects emerge.
The authors note that the article is a narrative review rather than a formal meta-analysis. As such, the conclusions synthesize and interpret existing literature rather than provide pooled quantitative estimates of effect. Important clinical recommendations—such as the suggested mid-normal therapeutic range of 350–550 ng/dL—are inferred from observational data and have not been evaluated in prospective randomized trials. The review therefore frames its guidance as interpretive, highlighting the need for individualized clinical judgment and further prospective research.
The review argues that both insufficient and excessive testosterone exposure may increase the risk of atrial fibrillation through separate mechanisms, creating a U-shaped risk relationship. For clinicians, the practical implications are to individualize TRT dosing, favor stable formulations, monitor hematocrit and cardiac rhythm, and address modifiable AF risk factors before and during therapy. The recommendations emphasize caution: therapeutic targets derived from observational data should be applied thoughtfully, and structured monitoring is advised to manage potential arrhythmic and hematologic risks associated with testosterone therapy.