QT interval changes in transgender/gender diverse adolescents receiving gonadotropin-releasing hormone agonist and gender-affirming hormonal treatment

Background: Hormones play a significant role in modulating cardiac electrophysiology. Gonadotropin-releasing hormone agonists (GnRHa) and gender-affirming hormonal treatment (GAHT) may impact QTc intervals, which could have clinical implications. Aim: To evaluate QTc interval changes in transgender/gender-diverse (TGD) adolescents undergoing GnRHa and GAHT. Methods: This prospective study included 39 TGD adolescents (20 females), mean age 15.6 ± 1.4 years, Tanner stage 4–5. QTc intervals were measured before and after GnRHa treatment and following GAHT initiation. Results: The mean QTc increased significantly from 382.4 ± 16.2 ms at baseline to 402.9 ± 20.1 ms after GnRHa treatment (p =.019) and remained prolonged at 402.8 ± 19.6 ms after estrogen addition (p =.988) in 10 TGD females, with an overall significant change across all treatment phases (p =.020). The mean QTc increased from 371.6 ± 15.4 ms to 380.8 ± 13.5 ms (p =.180) in 10 TGD females who initiated combined GnRHa and estrogen. Pooling both TGD female groups, mean QTc increased significantly from 377.0 ± 16.3 ms to 391.8 ± 19.9 ms after GnRHa and estrogen (p =.014). The mean QTc increased from 386.3 ± 15.5 ms at baseline to 398.8 ± 24.1 ms after GnRHa treatment (p =.178) and decreased significantly to 377.7 ± 18.1 ms after the addition of testosterone (p =.009) in 6 TGD males, with an overall significant change across all treatment phases (p =.010). The mean QTc decreased from 395 ± 20.3 ms to 385.2 ± 19.8 ms (p =.139) in 13-TGD males who initiated combined GnRHa and testosterone. Pooling both TGD male groups, mean QTc decreased significantly from 392.4 ± 19.0 ms to 382.8 ± 19.1 ms after GnRHa and testosterone (p =.044). Two participants, prescribed psychiatric medications exhibited a borderline/short QTc after adding testosterone. No arrhythmias were observed. Discussion and conclusion: QTc prolongation was observed in TGD female adolescents after the initiation of GnRHa, while TGD males showed a decrease in QTc following testosterone administration. Further studies on the clinical implications of QT interval changes in this population are warranted.