Too little or too much testosterone may matter for heart rhythm

Conflicting scientific trials and rising mechanistic proof are reshaping how researchers take into consideration testosterone ranges, alternative remedy, and the center’s electrical rhythm.

Association of testosterone and testosterone replacement therapy with atrial fibrillation: an updated review. Picture Credit score: Magic mine / Shutterstock

In a current overview printed within the Journal of the Endocrine Society, researchers investigated the consequences of serum testosterone ranges and testosterone alternative remedy (TRT) on the danger of atrial fibrillation (AF). The proof was not constant throughout research, however a number of experiences pointed to a better AF danger at each high and low testosterone ranges. This can be related when assessing AF danger in males receiving or contemplating TRT, though the affiliation nonetheless must be confirmed in future research.

Traditionally, research have linked low testosterone ranges to heightened AF danger in males, notably these aged 80 years and older. More moderen analysis has produced contrasting findings, suggesting that elevated testosterone ranges and TRT may additionally enhance AF danger. AF is extra frequent in males than girls and turns into more and more prevalent with age. Affected people could expertise appreciable morbidity and excessive healthcare prices. Methods to cut back the AF burden may due to this fact enhance particular person well being whereas easing the pressure on healthcare techniques.

In regards to the overview

Within the current structured narrative overview, researchers explored the rising affiliation between testosterone ranges, TRT, and atrial fibrillation.

The workforce searched the Embase and PubMed databases for related information printed in English by way of Might 4, 2026. They manually screened the reference lists of related publications to acquire supplemental data. The overview additionally thought of materials introduced on the 2024 European Society of Cardiology (ESC) Congress and the 2025 Joint Congress of the European Society of Endocrinology and the European Society for Pediatric Endocrinology (ECE/ESPE).

The researchers reviewed Meals and Drug Administration (FDA) security communications and public submissions associated to regulatory choices regarding testosterone remedy in the USA (US). The research included randomized managed trials (RCTs) evaluating cardiovascular outcomes of TRT use, in addition to systematic critiques with or with out meta-analyses of those trials. Giant-scale observational cohort research with testosterone measurements or TRT recipients have been additionally included.

The workforce included Mendelian randomization research, which use genetic variants to research doubtlessly causal associations, in addition to mechanistic investigations, society tips, consensus statements, and regulatory materials associated to TRT prescribing and labeling. They excluded narrative critiques that didn’t current unique analysis findings and thought of case experiences solely after they offered related data on regulatory choices or scientific tips.

The workforce recorded particulars on research design, participant traits, and the interventions examined. In addition they famous end result estimates, together with hazard ratios (HRs) and odds ratios (ORs), and in contrast these findings throughout the research. As a result of the included research differed considerably in design and populations, the findings have been synthesized narratively slightly than pooled, and no formal risk-of-bias scoring was carried out.

Outcomes

Within the 2023 TRAVERSE trial, AF occurred extra regularly amongst males receiving 1.62% transdermal testosterone gel than amongst these receiving placebo, though the AF evaluation was not adjusted for a number of comparisons. The boys enrolled within the research additionally had heart problems or a number of cardiovascular danger components. This differed from an earlier research in US veterans, which reported decrease AF danger after testosterone ranges have been introduced again to regular.

A 2024 meta-analysis of 106 RCTs discovered no statistically important enhance in AF. Actual-world findings have been additionally combined. A TriNetX-based replication didn’t affirm elevated AF danger, whereas a five-year cohort research discovered a roughly 27% increased AF hazard amongst cisgender males with hypogonadism receiving TRT. A 2024 evaluation of the UK Biobank (UKB) information and a publish hoc evaluation of the ASPirin in Lowering Occasions within the Aged (ASPREE) trial printed in the identical 12 months supported a non-linear affiliation between testosterone ranges and AF danger. Within the ASPREE trial, AF danger was almost doubled amongst older males within the highest two testosterone quintiles in contrast with these within the center quintile. Proof for the higher-testosterone finish of this relationship was extra constant than for the decrease finish.

Synthesizing the observational proof, the authors proposed that AF danger could also be lowest when whole serum testosterone ranges are roughly 350 to 550 ng/dL. This vary could present helpful context when deciphering the broader proof on testosterone-related cardiovascular danger, but it surely has not been prospectively validated as an AF-prevention threshold. These findings underscore the potential significance of sustaining testosterone throughout the mid-physiological vary whereas individualizing remedy targets.

Supporting these findings, mechanistic information, together with these obtained from mobile electrophysiology research performed in 2025, prompt a U-shaped relationship. The proposed mechanisms differ in accordance with testosterone focus. Decrease ranges could have an effect on calcium dealing with. At increased concentrations, testosterone could have an effect on potassium currents, shorten motion potential length, and favor the irregular electrical re-entry circuits that may maintain arrhythmias. Separate observational and genetic proof prompt that testosterone publicity may additionally be related to structural adjustments within the left atrium over time.

Schematic synthesis of the U-shaped relationship between serum testosterone and danger of incident AF, synthesized from the restricted cubic spline analyses of Xu et al (UK Biobank) (5) and Tran et al (ASPREE) (6). The curve is conceptual and doesn’t characterize a pooled quantitative estimate; the danger nadir lies throughout the mid-physiologic vary (shaded therapeutic window). In Tran et al, the elevated-risk affiliation at excessive testosterone was statistically important, whereas the low-testosterone affiliation didn’t attain significance. Axis conversion: 1 nmol/L = 28.82 ng/dL.

Conclusion

The findings spotlight a doable non-linear relationship between testosterone publicity and AF danger, whereas proof that TRT itself constantly will increase AF danger stays combined. This sample could also be clinically related when assessing AF danger and contemplating testosterone remedy. The outcomes may assist clinicians assess AF danger in hypogonadal males and inform TRT choice and monitoring.

Additional analysis may examine totally different TRT formulations over longer durations whereas additionally monitoring electrocardiograms, intercourse hormone-binding globulin (SHBG), and free testosterone ranges. This may occasionally make clear whether or not these components affect AF danger in a different way over time. One other space price exploring is how circumstances akin to diabetes, weight problems, hypertension, dyslipidemia, sleep apnea, thyroid problems, and liver or kidney impairment have an effect on AF danger in males receiving TRT.