Puberty Blockers Temporarily Slow Bone Growth, Recovery Seen With Hormone Therapy: JAMA

A systematic review and meta-analysis published in the journal of JAMA Pediatrics found that puberty suppression in transgender and gender-diverse adolescents temporarily slows bone development, particularly at the lumbar spine. While absolute bone mineral density remained stable during puberty suppression, it increased modestly after gender-affirming hormone therapy, with partial recovery of bone health when compared to peers.

Puberty represents a key window for achieving peak bone mass, which plays an important role in determining fracture risk later in life. As the use of puberty blockers and gender-affirming hormone therapy continues to expand in gender-diverse youth, understanding their long-term effects on skeletal health has become increasingly important.

A new systematic review and meta-analysis has found that while pubertal suppression with  temporarily slows bone mineral accrual in transgender and gender-diverse (TGD) adolescents, subsequent gender-affirming hormone therapy (GAHT) promotes substantial recovery in bone health. However, researchers say the extent of long-term "catch-up" remains uncertain, underscoring the importance of careful monitoring during treatment.

The study synthesized evidence from 10 longitudinal cohort studies involving 751 transgender and gender-diverse adolescents, including 427 individuals assigned female at birth (AFAB) and 324 assigned male at birth (AMAB). This study evaluated changes in bone mineral density (BMD), bone mineral apparent density (BMAD), and bone z scores measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck.

The analysis showed that during treatment with gonadotropin-releasing hormone agonists (GnRHa), lumbar spine z scores declined in both AFAB and AMAB adolescents, indicating slower bone mineral accrual when compared to age- and sex-assigned-at-birth reference populations. Despite these reductions in z scores, absolute bone mineral density remained largely stable throughout the pubertal suppression phase, suggesting that bone mass was maintained but did not increase at the pace expected during adolescence.

Lumbar spine z scores also improved, demonstrating partial recovery after hormone therapy. Nevertheless, average z scores at the end of follow-up remained numerically below pretreatment levels, although these differences were not consistently statistically significant across all skeletal sites. Recovery at the total hip and femoral neck was more variable, with greater differences observed between studies.

Adolescents with higher body mass index experienced more favorable bone measures, while shorter durations of GnRHa treatment and longer exposure to GAHT were associated with greater improvements in bone density. These findings suggest that minimizing unnecessary delays before initiating gender-affirming hormones, when clinically appropriate, may help optimize bone development during this critical period of growth.

Overall, current evidence does not demonstrate a persistent deficit in bone health after treatment but indicates a modest and uncertain shortfall in complete bone catch-up. They recommend regular assessment of bone health, timely initiation of GAHT following pubertal suppression when indicated, and supportive measures such as adequate nutrition, sufficient vitamin D intake, and regular weight-bearing physical activity to promote optimal skeletal development. The researchers also emphasize the need for longer-term studies to determine whether bone density fully normalizes into adulthood and how these changes may influence lifelong fracture risk.

Source:

Tienforti, D., Marinelli, L., Terrana, G., Di Geronimo, R., Spagnolo, L., Vervalcke, J., Ciancia, S., Baroni, M. G., Barbonetti, A., & T’Sjoen, G. (2026). Bone accrual during puberty suppression and gender-affirming therapy in transgender adolescents: A systematic review and meta-analysis: A systematic review and meta-analysis. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2026.2470