Sex Steroids and Cardiovascular Outcomes in Transgender Individuals: A Systematic Review and Meta-Analysis

Background: Transgender individuals receive cross-sex hormonal therapy to induce desired secondary sexual characteristics despite limited data regarding its effects on cardiovascular health.

Methods: A comprehensive search of several databases up to 7 April 2015 was conducted for studies evaluating the effect of sex steroid use on lipids, myocardial infarction, stroke, venous thromboembolism (VTE), and mortality in transgender individuals. Pairs of reviewers selected and appraised the studies. A random-effects model was used to pool weighted mean differences and 95% confidence intervals (CIs).

Results: We found 29 eligible studies with moderate risk of bias. In female-to-male (FTM) individuals, sex steroid therapy was associated with statistically significant increases in serum triglyceride (TG) levels at 3 to 6 months and at ≥24 months (21.4 mg/dL; 95% CI: 0.14 to 42.6) and in low-density lipoprotein cholesterol (LDL-C) levels at 12 months and ≥24 months (17.8 mg/dL; 95% CI: 3.5 to 32.1). High-density lipoprotein cholesterol (HDL-C) levels decreased significantly across all follow-up periods (highest at ≥24 months, -8.5 mg/dL; 95% CI: -13.0 to -3.9). In male-to-female (MTF) individuals, serum TG levels were significantly higher at ≥24 months (31.9 mg/dL; 95% CI: 3.9 to 59.9) without any changes in other parameters. Few myocardial infarction, stroke, VTE, and death events were reported (more frequently in MTF individuals).

Conclusions: Low-quality evidence suggests that sex steroid therapy may increase LDL-C and TG levels and decrease HDL-C level in FTM individuals, whereas oral estrogens may increase TG levels in MTF individuals. Data about important patient outcomes remain sparse.