Impact of Gonadotropin-releasing Hormone Analogue and Gender-affirming Hormone Therapy on Bone Mineral Density in Transgender Adolescents
DOI:
https://doi.org/10.12775/QS.2025.37.57200Keywords
transgender and gender diverse youth, puberty suppression, gonadotropin-releasing hormone analogue, gender-affirming hormone therapy, bone health, transgender and boneAbstract
Background: Sex hormones have a key impact on the development of the human body during puberty, including a significant influence on bone development - their shape, structure, length, and mineral density. Due to the growing number of transgender and gender diverse (TGD) adolescents and the increasing demand for gender-affirming hormone therapy (GAHT), there is rising curiosity about the impact of this therapy on the developing body of a young person.
Purpose: This review aims to summarize the latest scientific reports on the impact of gonadotropin-releasing hormone analogues (GnRHas) and GAHT on the bone mineral density (BMD) of transgender adolescents undergoing gender-changing therapies.
Findings: Low pretreatment BMD is more common among TGD adolescents than in the general population, and this is more prevalent in transgirls than in transboys. BMD Z-scores decline during treatment with GnRHas and respond differentially to GAHT. Regular follow-up and health advice are essential. Further long-term studies of the effects of these therapies on peak bone mass and future fracture risk are needed.
References
1. Kaltiala R, Bergman H, Carmichael P et al. Time trends in referrals to child and adolescent gender identity services: A study in four Nordic countries and in the UK. Nordic Journal of Psychiatry, 2020;74(1), 40–44.
2. Clark TC, Lucassen MF, Bullen P et al. The health and well-being of transgender high school students: Results from the New Zealand adolescent health survey (Youth’12). Journal of Adolescent Health. 2014;55(1), 93–99.
3. Eisenberg ME, Gower AL, McMorris BJ et al. Risk and protective factors in the lives of transgender/gender nonconforming adolescents. Journal of Adolescent Health. 2017;61(4), 521–526.
4. Kidd KM, Sequeira GM, Douglas C et al. Prevalence of gender-diverse youth in an urban school district. Pediatrics. 2021;147(6), e2020049823.
5. Wang Y, Yu H, Yang Y et al. Mental health status of cisgender and gender-diverse secondary school students in China. JAMA Network Open. 2020;3(10), e2022796.
6. Cheung AS, Zwickl S, Miller K, Nolan BJ, Wong AFQ, Jones P, Eynon N. The Impact of Gender-Affirming Hormone Therapy on Physical Performance. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e455-e465.
7. Coleman E, Radix AE, Bouman WP. et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgend Health. 2022;23(Suppl 1):S1‐S259.
8. Hembree WC, Cohen-Kettenis PT, Gooren L et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11), 3869–3903.
9. Tack LJW, Craen M, Lapauw B, et al. Proandrogenic and antiandrogenic progestins in transgender youth: differential effects on body composition and bone metabolism. J Clin Endocrinol Metab. 2018;103: 2147–2156.
10. Tack LJ, Craen M, Dhondt K, VandenBossche H, Laridaen J, Cools M. Consecutive lynestrenol and cross-sex hormone treatment in biological female adolescents with gender dysphoria: a retrospective analysis. Biol Sex Differ. 2016;7:14.
11. Tack LJW, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, et al. Consecutive cyproterone acetate and estradiol treatment in late-pubertal transgender female adolescents. J Sex Med. 2017;14(5):747–57.
12. Neyman A, Fuqua JS, Eugster EA. Bicalutamide as an androgen blocker with secondary effect of promoting feminization in male-to-female transgender adolescents. J Adolesc Health. 2019;64(4):544–6.
13. Bangalore Krishna K, Fuqua JS, Rogol AD et al. Use of Gonadotropin-Releasing Hrmone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357-372.
14. Irwig MS. Cardiovascular health in transgender people. Reviews in Endocrine and Metabolic Disorders. 2018;19(3), 243–251.
15. Maraka S, Singh Ospina N, Rodriguez-Gutierrez R et al. Sex steroids and cardiovascular outcomes in transgender individuals: A systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11), 3914–3923.
16. Alzahrani T, Nguyen T, Ryan A et al. Cardiovascular Disease Risk Factors and Myocardial Infarction in the Transgender Population. Circ Cardiovasc Qual Outcomes. 2019;12(4):e005597.
17. Kyinn M, Banks K, Leemaqz SY et al. Weight gain and obesity rates in transgender and gender-diverse adults before and during hormone therapy. Int J Obes (Lond). 2021;45(12):2562-2569.
18. Antun A, Zhang Q, Bhasin S et al. Longitudinal Changes in Hematologic Parameters Among Transgender People Receiving Hormone Therapy. J Endocr Soc. 2020;4(11):bvaa119.
19. Bland VL, Bea JW, Blew RM et al. Influence of Changes in Soft Tissue Composition on Changes in Bone Strength in Peripubertal Girls: The STAR Longitudinal Study. J Bone Mineral Res. 2021;36:123–32.
20. Weaver CM, Gordon CM, Janz KF et al. The National Osteoporosis Foundation's Position Statement on Peak Bone Mass Development and Lifestyle Factors: A Systematic Review and Implementation Recommendations. Osteoporosis Int. 2016;7:1281–386.
21. Seeman E. Pathogenesis of bone fragility in women and men. Lancet. 2002;359(9320):1841-50.
22. Saggese G, Baroncelli GI, Bertelloni S. Puberty and bone development. Best Practice and Research: Clinical Endocrinology and Metabolism. 2002;1653–64.
23. Banica T, Vandewalle S, Zmierczak HG et al.The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage. Bone. 2022;158 116368.
24. Melmed S, Koenig R, Rosen C, Auchus R, Goldfine A. Williams textbook of endocrinology, 14th Edition. Netherlands: Elsevier. 2019.
25. Shuhart CR, Yeap SS, Anderson PA et al. Executive Summary of the 2019 ISCD Position Development Conference on Monitoring Treatment, DXA Cross-calibration and Least Significant Change, Spinal Cord Injury, Peri-prosthetic and Orthopedic Bone Health, Transgender Medicine, and Pediatrics. J Clin Densitom. 2019;22(4):453-471.
26. McCormack SE, Cousminer DL, Chesi A, et al. Association between linear growth and bone accrual in a diverse cohort of children and adolescents. JAMA Pediatr. 2017;171(9):e171769.
27. 2019 ISCD Official Positions - Pediatric. The International Society for Clinical Densitometry. 2019.
28. Ciancia S, Dubois V, Cools M. Impact of gender-affirming treatment on bone health in transgender and gender diverse youth. Endocr Connect. 2022;11(11):e220280.
29. Bachrach LK, Gordon CM. & Section on Endocrinology. Bone densitometry in children and adolescents. Pediatrics 2016;138 e20162398.
30. van der Loos MA, Hellinga I, Vlot MC et al. Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty. J Bone Miner Res. 2021;36(5):931-941.
31. Rosen H, Hamnvik O-P, Jaisamrarn U et al. Bone densitometry in transgender and gender non-conforming (TGNC) individuals: 2019 ISCD official position. J Clin Densitom. 2019;22:544–53.
32. Lee JY, Finlayson C, Olson-Kennedy J et al. Low bone mineral density in early pubertal transgender/gender diverse youth: Findings from the Trans Youth Care Study. Journal of Endocrine Society. 2020. 4(9):bvaa065.
33. van der Loos MATC, Boogers LS, Klink DT et al. The natural course of bone mineral density in transgender youth before medical treatment; a cross sectional study. Eur J Endocrinol. 2024;191(4):426-432.
34. Hodax JK, Brady C, DiVall S, Ahrens KR, Carlin K, Khalatbari H, Parisi MT, Salehi P. Low Pretreatment Bone Mineral Density in Gender Diverse Youth. Transgend Health. 2023;8(5):467-471.
35. Vlot MC, Klink DT, den Heijer M et al. Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents. Bone. 2017;95:11-19.
36. Schagen SEE, Wouters FM, Cohen-Kettenis PT et al. Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones. J Clin Endocrinol Metab. 2020;105(12):e4252–63.
37. Navabi B, Tang K, Khatchadourian K, et al. Pubertal suppression, bone mass, and body composition in youth with gender dysphoria. Pediatrics. 2021;148: e2020039339.
38. Klink D, Caris M, Heijboer A et al. Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria. J Clin Endocrinol Metab. 2015;100(2):E270-5.
39. Johnson A, Miranda L, Lee M. Play to Win: Improving the Lives of LGBTQ Youth in Sports. Human Rights Campaign Foundation; 2017.
40. Bishop A, Overcash F, McGuire J, Reicks M. Diet and physical activity behaviors among adolescent transgender students: school survey results. J Adolesc Health. 2020;66(4):484-490.
41. Joseph T, Ting J, Butler G. The effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria: findings from a large national cohort. J Pediatr Endocrinol Metab. 2019;32(10):1077-1081.
42. Delemarre-van de Waal H, Cohen-Kettenis P. Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects. Eur J Endocrinol. 2006;155:S131–7.
43. Carmichael P, Butler G, Masic U, Cole T, De Stavola B, Davidson S, et al. Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PloS One. 2021;16:e0243894.
44. Stoffers IE, de Vries MC, Hannema SE. Physical changes, laboratory parameters, and bone mineral density during testosterone treatment in adolescents with gender dysphoria. J Sex Med. 2019;16(9):1459-1468.
45. Giacomelli G, Meriggiola MC. Bone health in transgender people: a narrative review. Ther Adv Endocrinol Metab. 2022;13:20420188221099346.
46. van der Loos MATC, Vlot MC, Klink DT, Hannema SE, den Heijer M, Wiepjes CM, et al. Bone mineral density in transgender adolescents treated with puberty suppression and subsequent gender-affirming hormones. JAMA Pediatr. 2023;177:1332–41.
47. Nokoff NJ, Bothwell S, Rice JD et al. Insulin sensitivity, body composition and bone mineral density after testosterone treatment in transgender youth with and without prior GnRH agonist therapy. J Clin Transl Endocrinol. 2024;36:100356.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Marta Chuncia-Ileczko, Witold Czyż, Julia Kacperczyk, Filip Arczewski, Karol Dziedzic, Julia Kulbacka, Maciej Wojszczyk, Damian Zys, Piotr Pasek, Julia Ryniecka
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 653
Number of citations: 0
