Abstract

Objective In this systematic review and meta-analysis, we assessed and summarised the certainty of the evidence about the effects of gender affirming hormone therapy (GAHT) in individuals with gender dysphoria (GD). Methods We searched Medline, Embase, PsychINFO, Social Sciences Abstracts, LGBTQ+ Source and Sociological Abstracts from inception to September 2023. We included studies comparing GAHT with no GAHT in individuals aged <26 years with GD. Outcomes of interest included psychological and physical effects. Pairs of reviewers independently screened articles, abstracted data and assessed the risk of bias in the included studies. We performed meta-analyses and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. Results We included 24 studies. Comparative observational studies (n=9) provided mostly very low certainty evidence regarding GD, global function and depression. One comparative observational study reported that the odds of depression may be lower (OR 0.73 (95% CI 0.61 to 0.88), n (number of studies)=1, low certainty) in individuals who received GAHT compared with those who did not. Before-after studies (n=13) provided very low certainty evidence about GD, global function, depression and bone mineral density. Case series studies (n=2) provided high certainty evidence that the proportion of individuals with cardiovascular events 7-109 months after receiving GAHT was 0.04 (95% CI 0.03 to 0.05, n=1, high certainty). Conclusion There is considerable uncertainty about the effects of GAHT and we cannot exclude the possibility of benefit or harm. Methodologically rigorous prospective studies are needed to produce higher certainty evidence. Trial registration number PROSPERO CRD42023452171.