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

Moderate and high serum estradiol rates of change were associated with increased body mass index in TNB adults using GAET.

• Moderate ROC (1 < ROC ≤ 3 pg/mL/mo) was associated with BMI increase of 0.40 kg/m² (95% CI: 0.22, 0.59 kg/m²; I² = 28.2%)
• High ROC (≥3 pg/mL/mo) was associated with BMI increase of 0.46 kg/m² (95% CI: 0.15, 0.78 kg/m²; I² = 0.0%)
• 19 studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5 studies; moderate = 6 studies; high = 8 studies)
• The systematic review and meta-analysis included 35 studies with 7,745 total participants

High serum estradiol rate of change was associated with decreased low-density lipoprotein levels.

• High ROC (≥3 pg/mL/mo) was associated with LDL decrease of -6.67 mg/dL (95% CI: -10.65, -2.68 mg/dL; I² = 0.0%)
• The abstract notes 'moderate to high rates of change were associated with decreases in low-density lipoprotein'
• Heterogeneity was zero (I² = 0.0%) for this association, indicating consistency across studies

Low and moderate serum estradiol rates of change were associated with decreases in systolic blood pressure.

• Low ROC (0 < ROC ≤ 1 pg/mL/mo) was associated with systolic blood pressure decrease of -7.05 mmHg (95% CI: -10.40, -3.70 mmHg; I² = 0.0%)
• Moderate ROC (1 < ROC ≤ 3 pg/mL/mo) was associated with systolic blood pressure decrease of -3.69 mmHg (95% CI: -4.93, -2.45 mmHg; I² = 0.0%)
• Heterogeneity was zero for both low and moderate ROC strata (I² = 0.0%)
• The low ROC stratum showed a numerically larger decrease in systolic blood pressure than the moderate ROC stratum

Cardiovascular-related deaths and adverse cardiovascular events were reported in only a small number of included studies.

• Two studies collectively reported 50 cardiovascular-related deaths
• Four studies collectively reported 23 adverse cardiovascular events
• These events were too few to be meta-analyzed and are reported descriptively

The systematic review included 35 studies across multiple designs examining serum estradiol levels and cardiovascular outcomes in TNB adults using GAET.

• Studies were identified from Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science from inception to April 2023
• The 35 included studies comprised 13 cross-sectional studies, 19 cohort studies, and 3 trials
• Total participant count across included studies was 7,745
• Data extraction was completed in duplicate following PRISMA guidelines
• Stratified random effects meta-analyses were used for longitudinal studies, stratified by rate of change (ROC) of serum estradiol