Prospective changes in depression and anxiety scores during the first year of gender-affirming hormone therapy in Denmark among transgender individuals with and without autism

Background: Transgender individuals experience elevated depression and anxiety symptoms, often linked to gender dysphoria. While gender-affirming hormone therapy (GAHT) alleviates dysphoria, its effect on depression and anxiety remains unclear. Autism is prevalent among transgender individuals and may influence mental health trajectories. Aims: To examine changes in depression and anxiety during the first year of GAHT, considering gender, follow-up duration, and autism status. Methods: In this prospective study, 160 transgender individuals (71 transmasculine, median age 23 years, and 89 transfeminine, median age 24 years) completed the Patient-Health-Questionnaire-8 and Generalized-Anxiety-Disorder-7 at baseline, six weeks, and one year after GAHT initiation. Eighteen percent had autism. Mixed linear models examined effects of time, gender, and autism, adjusting for age and education. Post-hoc analyses stratified participants by clinically relevant (CR) baseline symptom levels (≥10). Results: Baseline prevalence of CR depression was 34-42% and anxiety 16-32%. Overall, depression (β = −1.9) and anxiety (β = −1.1) decreased significantly (p <.001) after six weeks, returning to baseline after one year. However, those with baseline CR symptoms remained below baseline after one year (p <.05), whereas those without baseline CR symptoms exhibited increased scores after one year. Transmasculine reported higher anxiety than transfeminine individuals (β = −1.6, p =.010) across time. Autism did not significantly affect depression and anxiety symptom level or trajectory. Conclusions: Mental health changes during the first year of GAHT were modest and heterogeneous. Depression and anxiety symptom trajectories were primarily related to baseline mental health rather than gender or autism status, which underscores the importance of mental health screening during GAHT.