Age of initiation of gender affirming hormone therapy and mental health outcomes among transgender, non-binary, and gender diverse adults living in the U.S.

Abstract

Introduction: Gender-affirming hormone therapy (GAHT) has been associated with improved psychosocial well-being among transgender, non-binary, and gender-diverse (TGD) individuals. However, limited evidence exists on how the timing of initiation influences mental health in adulthood. This study examines the associations between GAHT initiation (age and desire) with depression and gender congruence indicators, in a national sample of TGD adults who identify as transfeminine in the United States. Methods: We conducted a secondary analysis of data from the 2022–2024 Transgender Women’s Internet Survey and Testing (TWIST) study. Participants were grouped by GAHT experience: (1) initiated before 18, (2) initiated at ≥18, (3) never initiated but desired, and (4) never initiated nor desired. Depression was measured using the PHQ-9 (cutoff ≥10). Gender identity–appearance alignment and comfort with how others perceive their gender were measured via self-report. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios (PRs), adjusting for sociodemographic covariates. Results: Among 5,178 adult respondents, 286 (5.5%) initiated GAHT in adolescence, 3,844 (74.2%) in adulthood, 841 (16.2%) desired but never accessed GAHT, and 207 (4.1%) neither initiated nor desired GAHT. The prevalence of moderate to severe depression among the four groups was 47.5%, 48.9%, 62.1%, and 56.0%, respectively. Alignment between gender identity and appearance, as well as comfort with how others perceive their gender, were highly prevalent among individuals who initiated GAHT during adolescence (69.9% and 57.9%, respectively), but less prevalent among those who desired but never accessed GAHT (22.3% and 15.7%). In adjusted models, all three comparison groups had significantly higher prevalence of depression and lower prevalence of gender congruence indicators than adolescent initiators (p < 0.05 for all comparisons). Notably, participants who desired but did not access GAHT demonstrated the greatest disparities in depression (adjusted PR = 1.45, 95% CI = 1.24, 1.69), appearance–identity alignment (adjusted PR = 0.32, 95% CI = 0.27, 0.38) and comfort with how others perceive their gender (adjusted PR = 0.28, 95% CI = 0.23, 0.34) when compared to those who initiated GAHT in adolescence. Discussion: Initiation of GAHT at any age was linked to more favorable outcomes; however, starting during adolescence appeared to confer additional mental health and gender congruence benefits. In comparison to early initiators, individuals who desired but never initiated it experienced the most pronounced psychosocial challenges. These findings highlight the importance of supporting timely access to GAHT—particularly for youth—and advancing affirming clinical and policy strategies to promote the well-being of TGD individuals.