Age-dependent bone mineral density responses to gender-affirming hormone therapy in transgender individuals: a one-year prospective study

Purpose: Evidence on the skeletal effects of gender-affirming hormone therapy (GAHT) in transgender individuals remains limited, especially across age groups. Individuals assigned male at birth (AMAB) often show reduced bone mineral density (BMD) even before GAHT, whereas findings in those assigned female at birth (AFAB) are more variable. Given the key role of adolescence and early adulthood in peak bone mass, timely skeletal assessment is essential. This study compared BMD before and after one year (1-y) of GAHT to age-matched cisgender controls. Methods: Prospective observational study involving 269 adults (162 transgender and 107 cisgender controls) conducted at the University Hospital of Padua (January 2020-November 2024). Dual-energy X-ray absorptiometry (DXA) was performed at baseline and after 1-y of GAHT. Results: After 1-y of GAHT, in AMAB individuals, lumbar spine BMD significantly increased (from 0.97 ± 0.16 to 1.02 ± 0.14 g/cm², p < 0.001), particularly in those under 20 years. AFAB individuals experienced a modest but significant reduction in femoral neck BMD (from 0.81 ± 0.12 to 0.79 ± 0.13, p < 0.05), especially in the 20–30-year age group. Age-stratified analyses revealed that younger participants showed greater BMD improvements, while those over 20 exhibited stable or declining values. Linear regression confirmed age as an independent predictor of BMD change, with older age associated with reduced skeletal responsiveness to GAHT at key femoral sites. Conclusions: GAHT has variable effects on bone health, influenced by age and sex assigned at birth. Early initiation may favor bone accrual, especially in AMAB individuals, while AFAB individuals may require closer monitoring for site-specific bone loss during testosterone therapy.