Gender-affirming hormone therapies (GAHTs) significantly affects cardiac repolarization in transgender individuals, with testosterone use in transgender men associated with QTc and QTp shortening and increased T-wave maximal amplitude (TAmp) and androgen deprivation in transgender women associated with QTc interval prolongation and decreased TAmp, according to a study published July 30 in JAMA.

Virginie Grouthier, MD, et al., conducted a cohort study using data from a prospective cohort of adult transgender individuals from a single center in France from Jan. 1, 2021 through Jan. 1, 2023, to examine the association between GAHT intake and cardiac repolarization alterations on electrocardiography in transgender women (assigned male at birth) and transgender men (assigned female at birth).

The study included 120 transgender individuals receiving GAHT. Within the TRANS and QT Polarization (QTrans) cohort, 76 individuals were already receiving GAHT at the inclusion visit and 44 were naïve at inclusion. The mean age of participants was 30 years and 64 were transgender men. GAHT was defined as injectable testosterone in transgender men and transdermal estradiol with mostly oral cyproterone acetate as antiandrogens in transgender women. Testosterone, estradiol, progesterone and gonadotrophins were assessed concomitantly to electrocardiographic intake, and electrocardiographic features including TAmp, QT peak (QTp) and QTc were examined.

Results showed that the mean QTc was similar between 23 transgender men before GAHT (400 ms) and 35 transgender women receiving GAHT (406 ms) but was prolonged vs. 41 transgender men receiving GAHT (378 ms) (p<0.001) or 21 transgender women before receiving GAHT (384 ms) (p<0.001). Additionally, increased QTc was associated with the start of GAHT in 15 transgender women, and decreased QTc in 18 transgender men. The authors note that no participant had a QTc >480 ms or QTc change >60 ms after the start of GAHT in this study.

"Our work highlights that potential GAHT effects on cardiac repolarization warrants attention in the exponentially increasing transgender population, which is often exposed to coprescribed drugs prolonging QTc and at risk of TdP, particularly transgender women," write the authors.

"By exploring the unique electrophysiologic mechanisms of transgender adults and the effects of GAHT, additional research can be generated specific to the GAHT received by cisgender adults," write Ayelet M. Shapira-Daniels, MD, and Carl Gustaf Streed Jr., MD, MPH, in an accompanying editorial comment. "While we call for more research to specifically explore the health of transgender adults, it remains to be seen if there is political will to truly make all [U.S.] residents healthy."

"Hormonal therapy's impact on corrected QT interval (QTc) is clinically important, with Grouthier et al., demonstrating that exogenous sex hormones used in gender-affirming hormone therapy affect QTc and related arrhythmia markers in transgender individuals similarly to their cisgender counterparts," says Matthew Carazo, MD, FACC. "Their study, notable for including gender minorities whose participation in cardiovascular research has been historically sparse, supports a shift from binary sex-based cardiovascular care toward personalized approaches that consider sex- and gender-specific factors and hormone exposures throughout life."