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

Abstract Cisgender women report higher stress than cisgender men, potentially due to psychosocial and biological factors, including sex hormone levels. Gender-affirming hormone therapy (GAHT) alters hormone levels, but its impact on perceived stress remains unclear. This study examined changes in perceived stress after 3 and 12 months of GAHT and potential differences between feminizing (FHT) and masculinizing hormone therapy (MHT). Data were drawn from two prospective cohort studies (ENIGI and RESTED) in the Netherlands, Belgium, and Israel. A total of 442 individuals (median age 23 years, IQR 20.5 to 28.0) completed the 10-item Perceived Stress Scale (PSS) before starting GAHT and after 3 and 12 months. Linear mixed models assessed changes after starting GAHT and differences between FHT and MHT groups. 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). Improvements in well-being during GAHT may not reduce perceived stress, potentially due to ongoing gender minority stressors. Future research should explore stressors and coping mechanisms to identify strategies for reducing perceived stress during GAHT.