ClinicalGeneralGender-affirming hormone treatment causes changes in gender phenotype in a 12-lead electrocardiogram
Graphical abstract
Introduction
A gender difference in lethal arrhythmias has been suggested by several lines of evidence: there is a predominance of males in patients with Brugada syndrome1 and patients with idiopathic ventricular fibrillation,2 females have a stronger association of QT prolongation with sudden cardiac death,3 and arrhythmic events occur earlier in males than in females with arrhythmogenic right ventricular cardiomyopathy.4 Although their contributions to different susceptibilities to arrhythmias are unclear, gender differences in baseline 12-lead electrocardiograms (ECGs) in healthy subjects have been recognized.5, 6, 7 Surawicz and Parikh5 defined male and female patterns in ECGs on the basis of J-point elevation and angle of the ST segment (see Methods). The percentage of men showing a typical male pattern decreases with aging, and androgen-deprivation therapy as a treatment for prostate carcinoma causes ECG changes from a male pattern to a female pattern,6 suggesting the involvement of androgen in the gender-specific ECG pattern. In addition to the high prevalence of a typical male pattern, young men have been shown to have unique ECG findings such as a high prevalence of an early repolarization (ER) pattern8, 9, 10, 11 and Sokolow-Lyon high voltage despite a lack of true left ventricular (LV) hypertrophy.12,13 Although these 3 findings are common in young men, the underlying mechanism has not been clarified yet.
Gender dysphoria (GD) is defined as distress and unease experienced if gender identity and designated gender are not completely congruent. Transgender males refer to individuals assigned female at birth but who identify and live as men, and transgender females are those assigned male at birth.14 Gender reassignment is a treatment procedure for those who want to adapt their bodies to the experienced gender through hormone therapy and/or surgery, and it is presumed that gender-affirming hormone treatment (GHT) has a significant influence on the heart.15 However, to our knowledge, there has been no published study in which the effect of GHT on the ECG or the risk of GHT for arrhythmia susceptibility has been assessed. Thus, this study aimed to investigate ECG changes induced by GHT in individuals with GD and to clarify the extrinsic sex hormone–mediated ECG changes.
Section snippets
Methods
The study protocol was approved by the Institutional Review Board of Sapporo Medical University (reference no. 302-207), and it conformed to the provisions of the Declaration of Helsinki.
GHT, mastectomy, and timing of the 12-lead ECG recording
The doses and intervals of an intramuscular injection of testosterone enanthate in transgender males at the time of the ECG recording were as follows: 125 mg every 2 weeks in 12 males and 125 mg every 3 weeks in 1 male, 250 mg every 2 weeks in 11 males, and 250 mg every 3 weeks in 2 males. Detailed information on dosage was not available in 3 males. The doses of estradiol in transgender females were as follows: 10 mg of intramuscular estradiol valerate every 2 weeks in 4 females, oral estradiol
GHT caused gender-specific changes in ECG parameters
Surawicz and Parikh5 showed that J-point elevation and ST-segment angle were stable in women at all ages but that they increased after puberty and reached peaks in men in their 20s. With further increase in age, these parameters decreased. Ezaki et al6 reported that J-point elevation in lead V2 in female subjects remained almost constant at all ages, but the J point in male subjects was significantly elevated while they were young. They also found that the J-point elevation was reduced by
Conclusion
GHT for GD has a substantial influence on ECG and converts the sex-related ECG phenotype. A sex hormone is likely to be responsible for the ECG changes induced by GHT.
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Funding sources: The authors have no funding sources to disclose.
Disclosures: The authors have no conflicts of interest to disclose.