Bone Mass Effects of Cross-Sex Hormone Therapy in Transgender People: Updated Systematic Review and Meta-Analysis

CONTEXT: The impact of long-term cross-sex hormone therapy (CSHT) in transgender men and women is still uncertain. OBJECTIVE: To perform a systematic review and meta-analysis and update the evidence regarding the effects of CSHT on bone mineral density (BMD) in transgender men and women. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, and Embase were searched for studies published until August 2018. STUDY SELECTION: Of 10,849 studies, 19 were selected for systematic review. All included patients were aged >16 years and received CSHT with BMD assessment by dual-energy X-ray absorptiometry (DXA). DATA EXTRACTION: Data on BMD, CSHT, and clinical factors affecting bone mass were collected. A National Institutes of Health scale was used to assess the quality of studies. DATA SYNTHESIS: Nineteen studies were meta-analyzed (487 trans men and 812 trans women). In trans men, mean BMD difference compared with natal women was not significant in any site in either cross-sectional or before-after studies. In trans women, mean BMD difference was not significant compared with natal men at the femoral neck, total femur, and lumbar spine in cross-sectional studies; before-after studies reported a slight but significant increase in lumbar spine BMD after 12 and ≥24 months of treatment. CONCLUSIONS: Long-term CSHT had a neutral effect on BMD in transgender men. In transgender women, only lumbar spine BMD seemed to be affected after CSHT. This evidence is of low to moderate quality as a result of the observational design of studies, small sample sizes, and variations in hormone therapy protocols.