Transgender-Affirming Hormone Therapies, QT Prolongation, and Cardiac Repolarization.

Mean QTc was significantly prolonged in transgender women receiving GAHT compared to transgender men receiving GAHT and transgender women before GAHT.

• Mean (SD) QTc in 35 transgender women receiving GAHT was 406 (20) milliseconds.
• Mean (SD) QTc in 41 transgender men receiving GAHT was 378 (19) milliseconds (P < .001 vs transgender women on GAHT).
• Mean (SD) QTc in 21 transgender women before GAHT was 384 (21) milliseconds (P < .001 vs transgender women on GAHT).
• Mean (SD) QTc in 23 transgender men before GAHT was 400 (16) milliseconds, similar to transgender women receiving GAHT.
• Overall cohort included 120 transgender individuals (mean [SD] age, 29.7 [11.9] years; 64 transgender men and 56 transgender women).

Initiation of GAHT in transgender women was associated with significant QTc prolongation.

• The start of GAHT in 15 transgender women was associated with increased QTc of mean (SD) 20 (12) milliseconds vs before receiving GAHT (P < .001).
• GAHT in transgender women consisted of transdermal estradiol with mostly oral cyproterone acetate as antiandrogens.
• No participant had a QTc greater than 480 milliseconds or QTc change greater than 60 milliseconds after the start of GAHT.

Initiation of GAHT in transgender men was associated with significant QTc shortening.

• The start of GAHT in 18 transgender men was associated with decreased QTc of mean (SD) -17 (16) milliseconds vs before receiving GAHT (P < .001).
• GAHT in transgender men consisted of injectable testosterone.
• No participant had a QTc change greater than 60 milliseconds after the start of GAHT.

In nonlinear mixed models, QTc in transgender men was independently associated with circulating total testosterone and prolactin levels.

• QTc was associated with total testosterone in transgender men with a mean (SD) estimate of -1.6 (0.6) ms/ng/mL (P = .007).
• QTc was associated with prolactin in transgender men with a mean (SD) estimate of 0.4 (0.1) ms/ng/mL (P < .001).
• Models integrated age, calcemia, relevant circulating hormone levels, and torsadogenic drug intake as covariates.

In nonlinear mixed models, QTc in transgender women was independently associated with circulating total testosterone levels.

• QTc in transgender women was associated with total testosterone with a mean (SD) estimate of -3.5 (0.8) ms/ng/mL (P < .001).
• The negative association indicates that lower testosterone (as achieved by androgen deprivation therapy) corresponded to longer QTc.
• Models integrated age, calcemia, relevant circulating hormone levels, and torsadogenic drug intake as covariates.

Changes in QT peak (QTp) and T-wave maximal amplitude (TAmp) after GAHT initiation mirrored QTc changes but in opposite directions between transgender women and transgender men.

• Variation of QTp and TAmp observed after the start of GAHT and associated hormonal alteration were globally associated with those observed with QTc.
• Changes were in opposite directions for transgender women and transgender men.
• Testosterone use in transgender men was associated with QTp shortening and increased TAmp.
• Androgen deprivation in transgender women was associated with opposite observations (QTp lengthening and decreased TAmp).

The magnitude of QTc sexual dimorphism observed in cisgender adults was reproduced in the transgender population undergoing GAHT.

• The difference in mean QTc between transgender women on GAHT (406 ms) and transgender men on GAHT (378 ms) was approximately 28 milliseconds.
• This difference mirrors the known QTc sexual dimorphism reported in cisgender adults.
• The authors state that 'the magnitude of QTc sexual dimorphism seen in cisgender adults was also observed in the transgender population.'

The transgender population is frequently exposed to co-prescribed QTc-prolonging drugs, raising concern about cumulative risk of torsades de pointes (TdP).

• The authors highlight that the transgender population is 'often exposed to coprescribed drugs prolonging QTc and at risk of TdP.'
• Data were collected from January 1, 2021, to January 1, 2023, from a single center in France.
• The study notes that the transgender population is 'exponentially increasing,' making GAHT cardiac repolarization effects a growing public health concern.
• Torsadogenic drug intake was included as a covariate in the nonlinear mixed models.