Endocrine regulation of cardiac repolarization: early QTc shortening after testosterone in healthy AFAB adults

Testosterone modulates ventricular repolarization, yet the early time course of its effects in humans remains unclear. We conducted a prospective, single-center study in 10 healthy adults assigned female at birth initiating gender-affirming hormone therapy with daily transdermal testosterone gel. Standard 12-lead ECGs at baseline and 3 months showed no change in uncorrected QT, but significant QTc shortening by Bazett (−32 ms; P = .002) and Fridericia (−14 ms; P = .010) formulas, despite a concurrent heart rate reduction and with no association to changes in serum testosterone. These findings demonstrate rapid ventricular repolarization remodeling after testosterone initiation, with a magnitude comparable to the sex-based QTc gap. This study contributes to the characterization of early electrophysiologic adaptation to androgens in a standardized clinical model, and may inform cardiovascular monitoring strategies during abrupt hormonal transitions.