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. 2025 May 14;16:1555186. doi: 10.3389/fendo.2025.1555186

Table 3B.

Summary of findings on bone outcomes of GnRHa treatment in TGD adolescents. Only studies with moderate-high level quality of evidence are included.

Reference Design/Population Intervention (duration) Bone mineral density Bone turnover
Carmichael 2021 (20) P/44
(25 AMAB, 19 AFAB)
GnRHa (29 m AFAB - 37 m AMAB) No change from baseline in LS BMD at 12 m nor in hip BMD at 24 and 36 m N/A
Schagen 2020 (21) P/121
(51 AMAB, 70 AFAB)
GnRHa (1.8 AFAB - 2.0 AMAB)
+ GAHT (3 y)
BMAD =/ ↓ during GnRHa 
↑ BMAD during GAHT
Z-scores normalized in AFAB but remained <0 in AMAB
P1NP↓/=, P3NP↓, osteocalcin↓, 1CTP↓
After 3 y of GAHT:
P1NP↓, P3NP↓/=, osteocalcin↓, 1CTP↓ 
Van der Loos 2023 (22) R/75 
(25 AMAB, 50 AFAB)
GnRHa  (1.5 y both AFAB and AMAB) 
+ GAHT (5.7 y AFAB - 5.3 y AMAB)
BMD Z-scores returned to pretreatment levels except LS Z-scores in AMAB N/A
Vlot 2017 (23) R/70
(28 AMAB, 42 AFAB)
GnRHa (1.5 y AFAB – 1.3 y AMAB)
+ GAHT (5.4 y AFAB – 5.8 y AMAB)
BMD Z-scores ↓ during GnRHa
↑after 24 m of GAHT 
↓P1NP and 1CTP during GnRHa

1CTP, cross-linked telopeptide of type 1 collagen; AFAB, assigned female at birth; AMAB, assigned male at birth; BMAD, bone mineral apparent density; BMD, bone mineral density; GAHT, gender-affirming hormone therapy; GnRHa, gonadotropin-releasing hormone analogues; LS, lumbar spine; m, months; N/A, not available; P, prospective; P1NP: procollagen type 1 N propeptide; P3NP, procollagen type 3 N propeptide; R, retrospective; TGD, transgender and gender-diverse; y, years.Arrow down: reduced; Arrow up: increased.