Age-Dependent Muscular Response to Testosterone-Based Gender-Affirming Therapy: Evidence from a 1-Year Observational Study

Objective: Age-related variability in the response to testosterone-based gender-affirming hormone therapy (GAHT) among transgender and gender-diverse individuals assigned female at birth (TGD AFAB) remains poorly understood. We investigated 1-year changes in muscle strength and mass after GAHT initiation and examined whether outcomes differ by age at treatment onset. Methods: In this prospective longitudinal observational study, a total of 107 TGD AFAB adults naïve to GAHT and gender-affirming surgeries were enrolled and stratified into four baseline age groups (20-24, 25-29, 30-34, and ≥35 years). Handgrip strength and body composition (dual-energy X-ray absorptiometry) were assessed at baseline and after 12 months of testosterone therapy. Within-group changes and age-related trends were evaluated using linear mixed models and quantile regression. Results: Handgrip strength increased after one year across all age groups, with a clear age-related gradient in magnitude. Gains were largest and significant in younger participants: +4.35 kg in the 25-29 group (p=0.001) and +2.14 kg in the 20-24 group (p=0.025). In the 30-34 and ≥35 groups, mean increases were smaller and not significant. Appendicular skeletal muscle mass index (ASMMI) showed modest, non-significant increases in younger participants and plateaued or declined from age 30 onward, with the 30-34 group displaying a decline most evident at the 25th percentile. Conclusions: Age at GAHT initiation markedly influences the anabolic response to testosterone therapy. Strength gains are more pronounced in early adulthood and decline with age, information that may assist clinicians in providing age-appropriate counseling for individuals beginning testosterone therapy.