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

ABSTRACT

INTRODUCTION: 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. METHODS: 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 (Low0RESULTS: 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%CI0.15, 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.

CONCLUSION:

In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.