Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (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 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect 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/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 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% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs 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.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

Measurements of Postmenopausal Serum Estradiol Levels and Cardiovascular Events: A Systematic Review.

Background: Cardiovascular disease (CVD) is the leading cause of death among female patients and its likelihood increases following menopause. However, whether estradiol levels are related to CVD remains unknown. We aimed to determine the association between serum estradiol levels and cardiovascular (CV) events in postmenopausal females. Methods: Electronic databases (MEDLINE, Embase) were searched systematically from inception to October 2022. Studies were eligible for inclusion if they included the following: (i) postmenopausal females; (ii) examination of the association between total serum estradiol levels and CV events (CV mortality, CVD, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, heart failure, and CV hospitalization); (iii) original data (randomized controlled trial, quasi-experimental, cohort, case-control, or cross-sectional study). A narrative synthesis was completed because the data were not amenable to meta-analysis. Results: Of the 9026 citations retrieved, 8 articles were included, representing a total of 5635 women. The risk-of-bias was fair, and considerable heterogeneity was present. In those not using menopausal hormone therapy, 3 studies demonstrated mixed results between estradiol levels and risk of coronary heart disease, and 1 study showed that higher estradiol levels were associated with an increased risk of myocardial infarction. No significant associations were present between estradiol levels and the remaining events (ie, CV mortality, heart failure, CVD, and stroke). Conclusions: The association between serum estradiol levels and CV events in postmenopausal females remains unclear. Further studies assessing this association are warranted, given the elevated CVD risk in this population.

Contexte: Les maladies cardiovasculaires (MCV) sont la principale cause de décès chez les femmes et leur probabilité augmente après la ménopause. Cependant, on ne sait pas encore si le taux d'estradiol est lié aux MCV. Nous avons tenté d'établir le lien entre le taux d'estradiol sérique et les événements cardiovasculaires (CV) chez les femmes post-ménopausées. Méthodologie: Nous avons consulté systématiquement des bases de données électroniques (MEDLINE, Embase) de leur création jusqu'en octobre 2022. Les études admissibles devaient comprendre les éléments suivants : i) femmes post-ménopausées; ii) examen du lien entre le taux total d'estradiol sérique et les événements CV (décès d'origine CV, MCV, coronaropathie, infarctus du myocarde, accident vasculaire cérébral (AVC), thromboembolie veineuse, insuffisance cardiaque et hospitalisation pour une cause CV); iii) données originales (essai contrôlé randomisé; études quasi expérimentales, de cohorte, cas-témoins ou transversales). Une synthèse narrative a été réalisée parce que les données ne se prêtaient pas à une méta-analyse. Résultats: Parmi les 9 026 citations relevées, 8 articles ont été retenus, représentant un total de 5 635 femmes. Le risque de biais était raisonnable, et une très grande hétérogénéité était présente. Chez les femmes qui ne suivaient pas d'hormonothérapie ménopausique, trois études ont affiché des résultats variables quant au lien entre le taux d'estradiol et le risque de coronaropathie, et une étude a montré que des taux élevés d'estradiol étaient associés à un risque accru d'infarctus du myocarde. Aucun lien notable n'a été observé entre le taux d'estradiol et les autres événements (c.-à-d. décès d'origine CV, insuffisance cardiaque, MCV et AVC). Conclusions: Le lien entre le taux d'estradiol sérique et les événements CV chez les femmes post-ménopausées n'a pas été élucidé. D'autres études sont nécessaires pour évaluer ce lien en raison du risque élevé de MCV au sein de cette population.