Gender-affirming hormone therapy and suicide-related outcomes in transgender and gender-diverse populations: a systematic review and meta-analysis

This systematic review and meta-analysis examined the association between gender-affirming hormone therapy (GAHT) and suicide-related outcomes (including suicidal ideation, suicide attempt, and suicide death) among transgender and gender-diverse individuals. It included 8 independent studies with 11 effect sizes. The pooled multilevel estimate was not statistically significant but pointed in a negative direction (log odds ratio = -0.3576; 95% confidence interval: -1.2768 to 0.5617; p=0.4458), suggesting a possible but not definitive protective effect of GAHT against suicidality. There was substantial heterogeneity among studies [Q (10)=170.5309, p<0.0001; σ2=1.7820; I2≈94.1%]. Moderator analyses showed that age group was significant [QM (2)=6.9350, p=0.0312], with mixed-age samples differing from adolescent samples, but adult samples did not significantly differ from adolescent samples. Comparator type, study design, and outcome domain were not significant moderators. Sensitivity analyses pointed to influential studies and evidence of funnel asymmetry and small-study effects. The conclusions highlight that while there is a non-significant trend toward a protective effect of GAHT, the evidence is limited by high heterogeneity, influential studies, small-study effects, and the predominantly observational nature of the data. Larger and better-characterized longitudinal studies are needed for clearer causal inference.

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