QTc Intervals in Gender Diverse Adolescents on Leuprolide Acetate

Background:
Leuprolide acetate, or Lupron, is a gonadotropin releasing hormone agonist commonly used to achieve pubertal suppression in gender diverse adolescents. Lupron is a fully reversible treatment that can halt the permanent changes of puberty and may help relieve gender dysphoria. There are concerns that Lupron prolongs the rate-corrected QT (QTc) interval when used as androgen deprivation therapy in the management of prostate cancer; however, there is a paucity of literature regarding Lupron and QTc interval in gender diverse adolescents. Our study aimed to evaluate QTc intervals in this population.

Methods:
We retrospectively reviewed data for youth between 9-18 years who were managed at the Stollery Endocrinology Gender Clinic (Edmonton, Alberta, Canada) between July 1, 2018 to December 31, 2019. A total of thirty-three pubertal adolescents were on Lupron and had a 12-lead electrocardiogram (ECG) obtained while on treatment. QTc intervals were analyzed, with QTc prolongation considered to be greater than 460 milliseconds (ms). When available, ECGs obtained prior to Lupron initiation were reviewed and the interval change was assessed. Data on concomitant medications and gender affirming hormones were obtained from the medical record.

Results:
Our cohort had a mean (SD) age of 13.7 (2.1) years and 69.7% identified as male after being assigned female at birth. None of the adolescents on Lupron demonstrated QTc interval prolongation. The mean (SD) QTc interval was 415 (27) ms. There were 8 adolescents (24.2%) with a QTc between 440 ms and 460 ms, categorized as borderline prolongation. Of these 8 adolescents, 6 (75%) were on concomitant psychotropic medications and 3 (37.5%) were on gender affirming hormones; 2 on oral estrogen and 1 on intramuscular testosterone. Of the 19 patients who had both a baseline and post-Lupron ECG, the mean (SD) QTc interval change was -4.77 (26.5) ms and 1 adolescent had an interval change greater than 40 ms. This patient identified as male, was on gender affirming therapy (intramuscular testosterone), and had an interval QTc increase of 44ms with their follow-up QTc being 448 ms.

Conclusion:
To our knowledge, this is the first study to report on QTc intervals in gender diverse adolescents on Lupron for pubertal suppression. Reassuringly, none of our cohort had QTc prolongation, defined as a QTc value greater than 460ms, or significant increase in QTc upon initiation of therapy. Borderline QTc prolongation was observed in 24.2% of adolescents and 62.5% of these patients were on at least 1 concomitant psychotropic medication classified as having a conditional risk for torsades de pointes.