Gender-affirming hormone therapy affects not only physical characteristics but also the heart's electrical activity, helping it align with a person's gender identity. This conclusion was reached by researchers who studied changes in heart function among transgender individuals.

The Impact of Hormone Therapy on the Body

Gender-affirming hormone therapy (GAHT) aims to bring a person's physical traits in line with their gender identity. Transgender women typically take antiandrogens and estrogen (or undergo castration) to reduce the effects of androgens like testosterone and promote feminization. Conversely, transgender men take testosterone to induce masculinization.

While there is some evidence suggesting a possible link between GAHT and an increased risk of cardiovascular disease, this connection is not yet fully understood. The new study focused on how GAHT influences the heart's electrical activity in transgender people.

What is the QT Interval and Why Is It Important?

On an electrocardiogram (ECG), the PQRST wave reflects the heart's electrical activity during a single heartbeat. The P wave shows atrial activation, the QRS complex represents ventricular activation, and the T wave indicates ventricular repolarization, or recovery after contraction.

The QT interval measures the time of ventricular contraction and relaxation and depends on heart rate: it shortens with a faster rhythm and lengthens with a slower one. To standardize this measurement, the heart rate-corrected QT interval (QTc) is used. Normal QTc values differ slightly between men and women: typically 350–450 ms for men and 360–460 ms for women. Deviations can indicate heart rhythm disorders, including the potentially dangerous condition Torsades de Pointes (TdP).

Study Design and Results

Between January 2021 and January 2023, 135 transgender individuals visited the endocrinology department at Bordeaux University Hospital in France. The study included 120 participants (64 trans men and 56 trans women), some of whom were already receiving GAHT. For 33 participants (18 trans men and 15 trans women), ECG data was available both before and after starting GAHT, allowing for a longitudinal analysis. Researchers recorded ECG parameters, including QTc, blood hormone levels (testosterone, estrogen, progesterone, prolactin, and gonadotropins), as well as other clinical data such as weight, blood pressure, and medication use. Patients with congenital long QT syndrome were excluded.

After starting testosterone, trans men experienced an average QTc shortening of 17 ms. In trans women, QTc lengthened by an average of 20 ms after beginning feminizing therapy. Higher testosterone levels were associated with shorter QTc, while lower levels correlated with QTc prolongation. These changes mirrored the typical sex differences seen between cisgender men and women, suggesting that GAHT can restore these patterns.

Researchers' Commentary

"In this study, feminizing GAHT was associated with QTc prolongation in trans women, while masculinizing GAHT led to QTc shortening in trans men," the authors noted. "The magnitude of these QTc changes was comparable to the known sex-based QTc dimorphism in cisgender adults."

Study Limitations

The study had several limitations. The sample size was relatively small, especially for subgroup analyses. Some participants lacked data on prolactin and progesterone. All patients were from a single medical center, which limits the generalizability of the results to broader populations or other healthcare systems. Additionally, the study was not designed to detect long-term arrhythmias due to the short observation period.

Practical Implications and Recommendations

The observed QTc changes were physiological rather than pathological and appeared to be determined by hormone levels, especially testosterone. These shifts reflected natural differences between cisgender men and women and did not pose an immediate risk. However, for trans women with prolonged QTc, caution is advised when prescribing other medications that can further lengthen the QT interval (such as certain antidepressants or antipsychotics), as this may increase the risk of arrhythmias. It is important to discuss this issue with a healthcare provider.

The study was published in JAMA Network Open.