Gender-affirming hormone therapies (GAHT) were associated with some cardiac repolarization alterations evident on electrocardiography (ECG), the QTrans cohort study showed.

ECG features were reported by Joe-Elie Salem, MD, PhD, of Assistance Publique-Hôpitaux de Paris, and colleagues based on 120 adult transgender patients from one French center:

• Corrected QT interval (QTc): mean 406 milliseconds in transgender women receiving GAHT, prolonged from 384 milliseconds in transgender women before GAHT; 378 milliseconds in transgender men on GAHT, down from 400 milliseconds in transgender men before GAHT
• QT peak (QTp): median 272 milliseconds in GAHT-treated transgender men, down from 298 milliseconds in GAHT-naive transgender men; 299 milliseconds in GAHT-treated transgender women, up from 265 milliseconds in GAHT-naive transgender women
• T-wave maximal amplitude (TAmp): median 1,122 μV in GAHT-treated transgender men, up from 854 μV in GAHT-naive transgender men; 886 μV in GAHT-treated transgender women, down from 1,075 μV in GAHT-naive transgender women
• PR interval, T-peak to T-end, and R-R interval were similar among these groups

“We found that feminizing GAHT used in transgender women was associated with a prolongation of QTc and QTp and a decrease in TAmp, whereas masculinizing GAHT used in transgender men was associated with opposite observations. The magnitude of ECG variations, particularly QTc observed among the studied transgender subgroups before and after GAHT, was within 15 to 20 milliseconds and mimicked the magnitude of sexual dimorphism observed in cisgender adults,” the investigators reported in JAMA Network Open.

“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 [torsade de pointes], particularly transgender women,” they concluded.

TdP, associated with abnormal QTc prolongation, is a feared ventricular arrhythmia that potentially leads to sudden death.

Study authors noted that it is typical for women to have QTc 10-20 milliseconds longer than men from puberty to menopause. Endogenous testosterone in men and progesterone in women are known to shorten QTc and thus protect against TdP. Hypogonadism in men thus prolongs their QTc, the authors explained.

They reported that no participant in the study had a QTc >480 milliseconds or QTc change >60 milliseconds after the start of GAHT.

Due to scarce evidence — what is known coming mainly from the congenital long QT syndrome literature — it is unclear how much longer a QTc has to be to truly confer a risk of TdP, suggested Ayelet Shapira-Daniels, MD, and Carl Gustaf Streed Jr, MD, MPH, both of Boston University Chobanian and Avedisian School of Medicine.

Physicians finding abnormal QT segments may thus have patients prematurely discontinue their GAHT, the duo suggested in an accompanying editorial.

Otherwise, they said, clinicians in the primary care setting are well equipped to use routine ECGs to monitor patients taking GAHT.

“Because GAHT is not typically considered QT prolonging, routine ECGs for patients receiving GAHT could serve as an easy practical tool available to primary care clinicians in ensuring safe prescribing, particularly if patients are taking other QT-prolonging medications, such as antidepressants, antipsychotics, or certain antibiotics. Empowering primary care clinicians to safely monitor GAHT use can also serve to reduce the barriers that transgender patients face when seeking care, often limited to specialists with additional training in transgender patient care,” according to Shapira-Daniels and Streed.

The QTrans cohort study had 120 adult transgender participants, counting 76 people already treated with GAHT and the other 44 GAHT-naive at baseline (the latter with 33 having a follow-up visit after start of GAHT).

Included were 64 transgender men and 56 transgender women. The GAHT-treated transgender women were significantly older relative to other patients (median 37 vs 23 years for other groups).

GAHT comprised injectable testosterone in transgender men versus transdermal estradiol with mostly oral cyproterone acetate as antiandrogens in transgender women.

Total testosterone had a negative correlation with QTc in transgender men and women alike; prolactin was also associated with QTc in transgender men alone.

Study authors warned of limited statistical power for some secondary analyses in their report.

“The small sample size and variability in GAHT medications used by the study participants substantially limit interpretation of the results,” agreed Shapira-Daniels and Streed. “Furthermore, in line with most studies encompassing transgender adults, participants were young, which is protective against TdP because QT prolongs with age.”

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