Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy
Authors: Nienke M. Nota, Chantal M. Wiepjes, Christel J.M. de Blok, Louis J.G. Gooren, Baudewijntje P.C. Kreukels, Martin den Heijer
Journal: Circulation (2019)

In hypogonadal/postmenopausal individuals, hormone therapy has been associated with an increased risk for cardiovascular events (CVEs).A steeply growing population that often receives exogenous hormones is transgender individuals.Although transgender individuals hypothetically have an increased risk of CVEs, there is little known about the occurrence of CVEs in this population. 1Therefore, we determined the incidences of acute/spontaneous strokes (ischemic/hemorrhagic, transient ischemic attack, or subarachnoid hemorrhage), myocardial infarctions (MIs), and venous thromboembolic events (VTEs) in transwomen and transmen receiving transgender hormone therapy (THT).Subsequently, we compared these incidences with those reported in women and men from the general population.This study was approved by our local ethical committee, with a waiver for informed consent.We reviewed the medical records of all 6793 individuals who visited our gender clinic between 1972 and 2015.However, we only included individuals who received THT prescribed by our center or an affiliate, whose date of start of THT was known, and who had at least 1 follow-up visit.We excluded participants who had discontinued THT for an extended period or who had used female and male sex hormones alternately.Of the remaining 3927 participants, the records were screened by physicians and medical students for letters/notes from physicians indicating clearly that an acute CVE had occurred.We excluded subjects who had experienced a CVE before starting THT (n=52).The final population consisted of 2517 transwomen (median age 30 years) and 1358 transmen (median age 23 years).From those who experienced multiple CVEs during THT (n=3), only the first event was taken into account.THT consisted of estrogens (±antiandrogens) in transwomen and testosterone in transmen.Adolescents usually received puberty suppressors, with the addition of THT from the age of 16 years.Statistical analyses were performed using OpenEpi version 3.01 (http://www.openepi.com)and Stata version 15.1 (https://www.stata.com).(Age-adjusted) standardized incidence ratios (SIRs) with 95% CIs were calculated using multiple steps.First, we determined the number of CVEs that occurred during THT (observed cases).Second, for each separate CVE, we created age groups comparable to those used by reference studies examining the occurrence of CVEs in the general Dutch or Norwegian populations, 2-4 and determined the follow-up duration (person-years) per age group.Third, we calculated overall expected cases, based on reported age-and sex-specific incidence rates by the reference studies, 2-4 and our age group-specific follow-up durations.Finally, Mid-P exact tests were performed.For transwomen, the total follow-up duration was 22 830 years.The mean and median follow-up durations were 9.07 (SD, 8.72) and 5.95 years (range, 0.01-54.77),respectively.For transmen, the total follow-up duration was 11 003 years.The mean and median follow-up durations were 8.10 years (SD, 8.82) and 4.10 years (range,