Association between Serum Estradiol and Cardiovascular Health among Transgender Adults Using Gender-Affirming Estrogen Therapy.

Abstract

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and non-binary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following PRISMA guidelines. Stratified random effects meta-analyses using serum estradiol ROC (serum estradiolbaseline-serum estradiolfollow-up/study duration) was used to assess longitudinal studies (Low:0<ROC≤1 pg/mL/month; Moderate:1<ROC≤3 pg/mL/month; High:ROC ≥3 pg/mL/month). Thirty-five studies (13 cross-sectional, 19 cohort, 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (Low=5; Moderate=6; High=8), demonstrating an association between moderate (0.40, 95%CI: 0.22, 0.59kg/m2, I2=28.2%) and high (0.46, 95%CI:0.15, 0.78kg/m2; I2=0.0%,) serum estradiol ROC and increased body mass index. High (-6.67, 95%CI:-10.65, -2.68mg/dL; I2=0.0%) serum estradiol ROC were associated with decreased low-density lipoproteins. Low (-7.05, 95%CI:-10.40, -3.70mmHg; I2=0.0%) and moderate (-3.69, 95%CI:-4.93, -2.45mmHg; I2=0.0%) serum estradiol ROC were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.