madman
Super Moderator
* Together, these observations add an important piece to the complex puzzle of how sex hormones influence atrial electrophysiology. In this context, the principle “dosis sola facit venenum” (the dose makes the poison) resonates strongly, suggesting that apparent discrepancies between studies may not be contradictory, but rather reflect different positions along the testosterone spectrum which seems to be non-linear.
Figure 1. Illustration depicting the hypothesized dose-dependent U-shape relationship between testosterone and atrial fibrillation risk and the potential underlying mechanisms. For a detailed description, please refer to the main text. AF, atrial fibrillation; APs, action potentials; DADs, delayed after depolarizations; FKBP, FK506 binding protein; RyR2, ryanodine receptor 2; SR, sarcoplasmic reticulum; TT, testosterone. The figure was created with BioRender.com
An emerging hypothesis that may reconcile these findings is a U-shaped association (Figure 1) in which both high and low testosterone levels promote arrhythmogenic remodeling through distinct mechanisms. On the one hand, testosterone-induced IK1 reduction, as demonstrated in the present study, may contribute to a more depolarized RMP and facilitate ectopic activity.1 This arrhythmogenic mechanism may be of particular importance in older men9, while in younger men, where testosterone levels are generally high, age-related factors, including general cardiovascular health, may act to protect against arrhythmia. On the other hand, testosterone may also exert protective effects, such as stabilizing RyR2 via FKBP12.68, and studies have shown that older men with low testosterone levels tend to have a higher incidence of AF.9 Notably, testosterone replacement in hypogonadal men has been associated with a decrease in AF incidence.10
Together, these observations add an important piece to the complex puzzle of how sex hormones influence atrial electrophysiology. In this context, the principle “dosis sola facit venenum” (the dose makes the poison) resonates strongly, suggesting that apparent discrepancies between studies may not be contradictory, but rather reflect different positions along the testosterone spectrum which seems to be non-linear. Further studies are necessary to deepen our understanding of the multifaceted effects of sex hormones on atrial electrophysiology.
Figure 1. Illustration depicting the hypothesized dose-dependent U-shape relationship between testosterone and atrial fibrillation risk and the potential underlying mechanisms. For a detailed description, please refer to the main text. AF, atrial fibrillation; APs, action potentials; DADs, delayed after depolarizations; FKBP, FK506 binding protein; RyR2, ryanodine receptor 2; SR, sarcoplasmic reticulum; TT, testosterone. The figure was created with BioRender.com
An emerging hypothesis that may reconcile these findings is a U-shaped association (Figure 1) in which both high and low testosterone levels promote arrhythmogenic remodeling through distinct mechanisms. On the one hand, testosterone-induced IK1 reduction, as demonstrated in the present study, may contribute to a more depolarized RMP and facilitate ectopic activity.1 This arrhythmogenic mechanism may be of particular importance in older men9, while in younger men, where testosterone levels are generally high, age-related factors, including general cardiovascular health, may act to protect against arrhythmia. On the other hand, testosterone may also exert protective effects, such as stabilizing RyR2 via FKBP12.68, and studies have shown that older men with low testosterone levels tend to have a higher incidence of AF.9 Notably, testosterone replacement in hypogonadal men has been associated with a decrease in AF incidence.10
Together, these observations add an important piece to the complex puzzle of how sex hormones influence atrial electrophysiology. In this context, the principle “dosis sola facit venenum” (the dose makes the poison) resonates strongly, suggesting that apparent discrepancies between studies may not be contradictory, but rather reflect different positions along the testosterone spectrum which seems to be non-linear. Further studies are necessary to deepen our understanding of the multifaceted effects of sex hormones on atrial electrophysiology.
