Effect of Sex Steroids on the Bone Health of Transgender Individuals: A Systematic Review and Meta-Analysis

Background: The impact of sex steroids on bone health in transgender individuals is unclear. Methods: A comprehensive search of several databases to 7 April 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CIs). Results: Thirteen studies evaluating 639 transgender individuals were identified [392 male-to-female (MTF), 247 female-to-male (FTM)]. In FTM individuals and compared with baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck, or total hip bone mineral density (BMD) when assessed at 12 and 24 months. In MTF individuals and compared with baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm(2); 95% CI, 0.03 to 0.06 g/cm(2)) and 24 months (0.06 g/cm(2); 95% CI, 0.04 to 0.08 g/cm(2)). Fracture rates were evaluated in a single cohort of 53 MTF and 53 FTM individuals, with no events at 12 months. The body of evidence is derived mostly from observational studies at moderate risk of bias. Conclusion: In FTM individuals, masculinizing hormone therapy was not associated with significant changes in BMD, whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient-important outcomes such as fracture risk is uncertain.