Aims: To characterise longitudinal changes in bone density and microarchitecture over 24 months in transgender adults receiving gender-affirming hormone therapy (GAHT).
Methods: Prospective cohort study. Transgender adults aged ≥18 years commencing standard-dose estrogen-based (E-GAHT) or testosterone-based (T-GAHT) GAHT were enrolled alongside cisgender controls. Outcomes were changes in cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture by HR-pQCT, areal BMD by DXA, and bone remodelling biochemistry over 24 months.
Results: 181 participants were enrolled: 37 E-GAHT, 41 T-GAHT, 50 cis women, 53 cis men. GAHT rapidly shifted sex steroids to target range in both trans groups by 3 months, sustained to 24 months. In E-GAHT, bone remodelling declined: CTX fell 409 to 328 ng/L and P1NP 61.0 to 42.0 µg/L by 24 months, consistent with a low-turnover state; total vBMD was broadly preserved at both sites, but cortical area at the distal tibia was 18.1 mm² smaller than cis male controls (95% CI −33.9 to −2.3; P=0.004), with trabecular density modestly maintained. In T-GAHT, bone formation markers rose markedly by 3 months (P1NP +37%), and total vBMD at the distal tibia increased progressively (group×time interaction P<0.0001 vs cis women), with microarchitecture shifting toward the male pattern. Across both groups, bone changes moved from the birth-assigned toward the affirmed-gender pattern, without fully reaching it by 24 months.
Conclusion: Twenty-four months of GAHT produced direction-consistent shifts in bone turnover and microarchitecture in both groups. E-GAHT showed a cortical area deficit at the weight-bearing tibia, with trabecular bone broadly preserved. T-GAHT showed progressive androgen-driven bone accrual at weight-bearing sites without net bone loss. These findings suggest no clinically meaningful bone loss over 24 months of contemporary GAHT and identify cortical bone at weight-bearing sites in trans women as a priority for clinical monitoring and further research.