Perceived stress during gender-affirming hormone therapy: a comparative study of feminizing and masculinizing hormone therapy in an international multicenter prospective cohort.

Gender-affirming hormone therapy (GAHT) can improve mental wellbeing, but psychological responses to GAHT may differ between feminizing (FHT) and masculinizing hormone therapy (MHT). The effects of GAHT on perceived stress, particularly over time, remain underexplored. This study examined (1) within-person changes in perceived stress after 3 and 12 months of GAHT and (2) potential differences in stress trajectories between individuals initiating FHT and MHT. Data were used from two prospective cohort studies (ENIGI and RESTED) in the Netherlands, Belgium, and Israel. In total, 442 individuals (median age 23 years, IQR 20.5-28.0) completed the 10-item Perceived Stress Scale before GAHT and after 3 and 12 months. Linear mixed models assessed changes over time and between-group differences. Baseline perceived stress levels did not significantly differ between groups (0.15, p = 0.84). No significant changes in perceived stress were observed after 3 or 12 months, nor were there significant differences in changes between FHT and MHT (-1.0, p = 0.21; 0.25, p = 0.76). Within the limits of the present study, we observed no significant changes in perceived stress. Future research should explore stressors and coping mechanisms to identify strategies for reducing perceived stress during GAHT.