Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter August 31, 2019

The effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria: findings from a large national cohort

  • Tobin Joseph , Joanna Ting and Gary Butler EMAIL logo



More young people with gender dysphoria (GD) are undergoing hormonal intervention starting with gonadotropin-releasing hormone analogue (GnRHa) treatment. The impact on bone density is not known, with guidelines mentioning that bone mineral density (BMD) should be monitored without suggesting when. This study aimed to examine a cohort of adolescents from a single centre to investigate whether there were any clinically significant changes in BMD and bone mineral apparent density (BMAD) whilst on GnRHa therapy.


A retrospective review of 70 subjects aged 12–14 years, referred to a national centre for the management of GD (2011–2016) who had yearly dual energy X-ray absorptiometry (DXA) scans. BMAD scores were calculated from available data. Two analyses were performed, a complete longitudinal analysis (n=31) where patients had scans over a 2-year treatment period, and a larger cohort over the first treatment year (n=70) to extend the observation of rapid changes in lumbar spine BMD when puberty is blocked.


At baseline transboys had lower BMD measures than transgirls. Although there was a significant fall in hip and lumbar spine BMD and lumbar spine BMAD Z-scores, there was no significant change in the absolute values of hip or spine BMD or lumbar spine BMAD after 1 year on GnRHa and a lower fall in BMD/BMAD Z-scores in the longitudinal group in the second year.


We suggest that reference ranges may need to be re-defined for this select patient cohort. Long-term BMD recovery studies on sex hormone treatment are needed.

Corresponding author: Professor Gary Butler, Department of Paediatric and Adolescent Endocrinology, University College London Hospital, 250 Euston Road, London NW1 2PQ, UK; UCL Great Ormond Street Institute of Child Health, London, UK; and Gender Identity Development Service, Tavistock and Portman NHS Trust, London, UK, Phone: +44 (0)20 344 79455


We are grateful to the staff from the Department of Nuclear Medicine UCLH for conducting the scans; colleagues from the National Adolescent Gender Identity Development Service, Tavistock and Portman NHS Trust for the assessment and referral of subjects; Elaine Perkins, Professor Russell Viner, Dr Elena Monti and the adolescent endocrine team at UCLH, and Professor Mary Fewtrell UCL for guidance on the analysis.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. The project was conceived by GB. Data collection and analysis was conducted by TJ and JT with input from GB as part of a UCL Medical School academic programme.

  2. Research funding: None. All scans were conducted as part of the NHS routine care programme.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Susman EJ, Houts RM, Steinberg L, Belsky J, Cauffman E, et al. Longitudinal development of secondary sexual characteristics in girls and boys between ages 91/2 and 151/2 years. Arch Pediatr Adolesc Med 2010;164:166–73.10.1001/archpediatrics.2009.261Search in Google Scholar PubMed PubMed Central

2. Bonjour JP, Theintz G, Buchs B, Slosman D, Rizzoli R. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 1991;73:555–63.10.1210/jcem-73-3-555Search in Google Scholar PubMed

3. Butler G, De Graaf N, Wren B, Carmichael P. Assessment and support of children and adolescents with gender dysphoria. Arch Dis Child 2018;103:631–6.10.1136/archdischild-2018-314992Search in Google Scholar PubMed

4. Klink D, Caris M, Heijboer A, Van Trotsenburg M, Rotteveel J. 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:E270–5.10.1210/jc.2014-2439Search in Google Scholar PubMed

5. Vlot MC, Klink DT, den Heijer M, Blankenstein MA, Rotteveel J, 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;95:11–9.10.1016/j.bone.2016.11.008Search in Google Scholar PubMed

6. Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2017;102:3869–903.10.1210/jc.2017-01658Search in Google Scholar PubMed

7. Levine MA. Assessing bone health in children and adolescents. Indian J Endocrinol Metab 2012;16(Suppl 2):S205–12.10.4103/2230-8210.104040Search in Google Scholar PubMed PubMed Central

8. Crabtree NJ, Shaw NJ, Bishop NJ, Adams JE, Mughal MZ, Arundel P, et al. Amalgamated reference data for size-adjusted bone densitometry measurements in 3598 children and young adults – the ALPHABET study. J Bone Miner Res 2017;32:172–80.10.1002/jbmr.2935Search in Google Scholar PubMed PubMed Central

9. Van Caenegem E, Wierckx K, Taes Y, Dedecker D, Van de Peer F, et al. Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy. J Clin Endocrinol Metab 2012;97:2503–11.10.1210/jc.2012-1187Search in Google Scholar PubMed

10. Boot AM, de Ridder MA, Pols HA, Krenning EP, de Muinck Keizer-Schrama SM. Bone mineral density in children and adolescents: relation to puberty, calcium intake, and physical activity. J Clin Endocrinol Metab 1997;82:57–62.10.1210/jc.82.1.57Search in Google Scholar PubMed

11. Baroncelli GI, Bertelloni S, Sodini F, Saggese G. Osteoporosis in children and adolescents etiology and management. Pediatr Drugs 2005;7:295–323.10.2165/00148581-200507050-00003Search in Google Scholar PubMed

12. Cohen-Kettenis PT, Klink D. Adolescents with gender dysphoria. Best Pract Res Clin Endocrinol Metab 2015;29:485–95.10.1016/j.beem.2015.01.004Search in Google Scholar PubMed

Received: 2019-01-22
Accepted: 2019-07-17
Published Online: 2019-08-31
Published in Print: 2019-10-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 24.2.2024 from
Scroll to top button