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

Chantal L Rytz; Keila Turino Miranda; Paul E Ronksley; Nathalie Saad; Satish R Raj; Ranjani Somayaji; Sandra M Dumanski; Heather Ganshorn; Dina N Greene; David Collister; Amelia M Newbert; Lindsay Peace; Sofia B Ahmed

doi:10.1152/ajpheart.00151.2024

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

Am J Physiol Heart Circ Physiol. 2024 Apr 5. doi: 10.1152/ajpheart.00151.2024. Online ahead of print.

Authors

Affiliations

¹ University of Calgary, Calgary, Alberta, Canada.
² McGill University, Canada.
³ University of Calgary, Canada.
⁴ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada.
⁶ University of Calgary, Calgary, Canada.
⁷ Department of Laboratory Medicine, University of Washington, United States.
⁸ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
⁹ Skipping Stone Foundation, Calgary, Alberta, Canada.
¹⁰ Skipping Stone Foundation, Calgary, AB, Canada.
¹¹ University of Alberta, Edmonton, Alberta, Canada.

PMID: 38578239
DOI: 10.1152/ajpheart.00151.2024

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 estradiol_baseline-serum estradiol_follow-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).

Results: 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.

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

Keywords: cardiovascular; gender-affirming estrogen therapy; rate of change; serum estradiol; transgender women.