Main Article Content
Gender dysphoria, transgender, adolescents, Gn-RH analogue, gender affirming hormones
Over the last decade, we have witnessed a significant rise in the number of transgender young people seeking endocrine treatment, of which clinical service and gender dysphoria terminology have attempted to keep pace both in matching demand and better describing the condition. Although helpful guidelines for pubertal suppression and gender affirming hormones have been developed, uncertainties remain regarding treatment and monitoring during treatment, often because the clinical needs of the transgender population have outpaced medical expertise and training. Recently, multidisciplinary team work has evolved due to the increasing complexity of diagnostic and treatment decision-making and has been instrumental in creating a unique service with input from a range of specialists. In this article, the current approach in clinical management of adolescents with gender dysphoria is reviewed, with focus on the endocrine aspect of care in children and adolescents. Questions on what defines optimal clinical care of children and adolescents with gender dysphoria remain and should be the focus of future research.
2. Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:3869-3903.
3. Martinerie L, Condat A, Bargiacchi A, Bremont-Weill C, de Vries MC, Hannema SE. Management of Endocrine Disease: Approach to the management of children and adolescents with Gender Dysphoria. Eur J Endocrinol. 2018;179:R219-R237.
4. T'Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of Transgender Medicine. Endocr Rev. 2019;40:97-117.
5. American Psychiatric Association. The Diagnostic and Statistical Manual of Mental Disorders (5th ed.) 2013. Arlington, VA: American Psychiatric Publishing.
6. Ristori J, Steensma TD. Gender dysphoria in childhood. Int Rev Psychiatry. 2016;28:13-20.
7. Cohen-Kettenis PT, Owen A, Kaijser VG, Bradley SJ & Zucker KJ. Demographic characteristics, social competence, and behavior problems in children with gender identity disorder: a cross-national, cross-clinic comparative analysis. J Abnorm Child Psych. 2003;31:41-53.
8. Steensma TD, Zucker KJ, Kreukels BPC, VanderLaan DP, Wood H, Fuentes A, Cohen-Kettenis PT. Behavioral and Emotional Problems on the Teacher’s Report Form: A Cross-National, Cross-Clinic Comparative Analysis of Gender Dysphoric Children and Adolescents. J Abnorm Child Psych. 2014;42:635-647.
9. Steensma TD, Biemond R, de Boer F, Cohen-Kettenis PT. Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. Clin Child Psychol Psychiatry. 2011;16:499-516.
10. Steensma TD, McGuire JK, Kreukels BP, Beekman AJ, Cohen-Kettenis PT. Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry. 2013;52:582-590.
11. Littman L. Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria. PLoS One. 2018:13(8):e0202330.
12. Zucker KJ. Adolescents with Gender Dysphoria: Reflections on Some Contemporary Clinical and Research Issues. Arch Sex Behav. 2019;48:1983-1992.
13. Brandelli Costa A. Formal comment on: Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria. PLoS One. 2019;14(3):e0212578.
14. Restar AJ. Methodological Critique of Littman's (2018) Parental-Respondents Accounts of "Rapid-Onset Gender Dysphoria". Arch Sex Behav. 2019 Apr 22. doi: 10.1007/s10508-019-1453-2.
15. Hutchinson A, Midgen M & Spiliadis A. In Support of Research Into Rapid-Onset Gender Dysphoria. Arch Sex Behav. 2019 Jul 17. doi: 10.1007/s10508-019-01517-9.
16. Clements-Nolle K, Marx R & Katz M. Attempted suicide among transgender persons: the influence of gender-based discrimination and victimization. J Homosexual. 2006; 51:53-69.
17. Connolly MD, Zervos MJ, Barone CJ II, Johnson CC, Joseph CL. The mental health of transgender youth: advances in understanding. J Adolesc Health. 2016;59:489-495.
18. Edwards-Leeper L, Spack NP. Psychological evaluation and medical treatment of transgender youth in an interdisciplinary “Gender Management Service” (GeMS) in a major pediatric center. J Homosexual. 2012;59:321-336.
19. Becerra-Culqui TA, Liu Y, Nash R, Cromwell L, Flanders WD , Getahun D , Giammattei SV , Hunkeler EM, Lash TL , Millman A , Quinn VP , Robinson B, Roblin D, Sandberg DE , Silverberg MJ , Tangpricha V , Goodman M . Mental Health of transgender and gender non-conforming youth compared with their peers.Pediatrics.2018 2018;141(5):e20173845.
20. Van Der Miesen AI, Hurley H, De Vries ALC. Gender dysphoria and autism spectrum disorder: A narrative review. Int Rev Psychiatry. 2016;28:70-80.
21. Glidden D, Bouman WP, Jones BA, Arcelus J. Gender Dysphoria and Autism Spectrum Disorder: A Systematic Review of the Literature. Sex Med Rev. 2016 ;4:3-14.
22. Thrower E, Bretherton I, Pang KC, Zajac JD, Cheung AS. Prevalence of Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder Amongst Individuals with Gender Dysphoria: A Systematic Review. J Autism Dev Disord. 2019;10.1007/s10803-019-04298-1.
23. Sterzing PR, Ratliff GA, Gartner RE, McGeough BL, Johnson KC. Social Ecological Correlates of Polyvictimization among a National Sample of Transgender, Genderqueer, and Cisgender Sexual Minority Adolescents. Child Abuse Negl. 2017;67:1-12.
24. Shields JP, Cohen R, Glassman JR, Whitaker K, Franks H, & Bertolini I. Estimating population size and demographic characteristics of lesbian, gay, bisexual, and transgender youth in middle school. J Adolesc Health. 2013;52:248-250.
25. Clark TC, Lucassen MFG, Bullen P, Denny SJ, Fleming TM, Robinson EM & Rossen FV. The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12). J Adolesc Health. 2014;55:93-99.
26. Eisenberg ME, Gower AL, McMorris BJ, Rider G., Shea G & Coleman E. Risk and Protective Factors in the Lives of Transgender/Gender Nonconforming Adolescents. J Adolesc Health. 2017;61:521-526.
27. Zucker KJ. Epidemiology of gender dysphoria and transgender identity. Sex. Health. 2017;14:404-411.
28. Butler G, De Graaf N, Wren B, Carmichael P. Assessment and support of children and adolescents with gender dysphoria. Arch Dis Child. 2018;103:631-636.
29. Skordis N, Butler G, de Vries MC, Main K & Hannema SE. ESPE and PES International Survey of Centers and Clinicians Delivering Specialist Care for Children and Adolescents with Gender Dysphoria. Horm Res Paediatr. 2018;90:326-331.
30. Fielding J, Bass C. Individuals seeking gender reassignment: marked increase in demand for services. BJPsych Bulletin. 2018;42:206-210.
31. Aitken M, Steensma TD, Blanchard R, VanderLaan DP, Wood H, Fuentes A, et al. Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. J Sex Med. 2015;12:756-763.
32. Arnoldussen M, Steensma TD, Popma A, van der Miesen AIR, Twisk JWR, de Vries ALC. Re-evaluation of the Dutch approach: are recently referred transgender youth different compared to earlier referrals? Eur Child Adolesc Psychiatry. 2019;10.1007/s00787-019-01394-6.
33. de Vries ALC, McGuire JK, Steensma TD, Wagenaar EC, Doreleijers TA, Cohen-Kettenis PT. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics. 2014;134:696-704.
34. Costa R, Carmichael P & Colizzi M. To treat or not to treat: puberty suppression in childhood-onset gender dysphoria. Nat Rev Urol. 2016;13:456-462.
35. Cohen-Kettenis PT, van Goozen SH. Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur Child Adolesc Psychiatry. 1998;7:246-248.
36. Schagen SEE, Cohen-Kettenis PT, Delemarre-van de Waal HA, Hannema SE. Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents. J Sex Med. 2016;13:1125-1132.
37. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, ESPE-LWPES GnRH Analogs Consensus Conference Group, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123:e752-762.
38. Shumer DE, Nokoff NJ, Spack NP. Advances in the Care of Transgender Children and Adolescents. Adv Pediatr. 2016;63:79-102.
39. Costa R, Dunsford M, Skagerberg E, Holt V, Carmichael P, Colizzi M. Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria. J Sex Med. 2015;12:2206-2214.
40. Panagiotakopoulos L. Transgender medicine - puberty suppression. Rev Endocr Metab Dis. 2018;19:221-225.
41. Lee JW, Kim HJ, Choe YM, Kang HS, Kim SK, Jun YH, Lee JE. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty. Ann Pediatr Endocrinol Metab. 2014;19:135-140.
42. 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:E270-275.
43. Vlot MC, Klink DT, den Heijer M, Blankenstein MA, Rotteveel J, Heijboer AC. 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.
44. Staphorsius AS, Kreukels BP, Cohen-Kettenis PT, Veltman DJ, Burke SM, Schagen SE, Wouters FM, Delemarre-van de Waal HA, Bakker J. Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria. Psychoneuroendocrinology. 2015;56:190-199.
45. Hough D, Bellingham M, Haraldsen IR, McLaughlin M, Robinson JE, Solbakk AK, Evans NP. A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep. Psychoneuroendocrinology. 2017;77:1-8.
46. Hough D, Bellingham M, Haraldsen IRH, McLaughlin M, Rennie M, Robinson JE, Solbakk AK, Evans NP. Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep. Psychoneuroendocrinology. 2017;75:173-182.
47. Hough D, Robinson JE, Bellingham M, Fleming LM, McLaughlin M, Jama K, Haraldsen I, Solbakk AK, Evans NP. Peripubertal GnRH and testosterone co-treatment leads to increased familiarity preferences in male sheep. Psychoneuroendocrinology. 2019;108:70-77.
48. Olson-Kennedy J, Chan YM, Rosenthal S, Hidalgo MA, Chen D, Clark L, Ehrensaft D, Tishelman A, Garofalo R. Creating the Trans Youth Research Network: A Collaborative Research Endeavor. Transgend Health. 2019;4:304-312.
49. de Ronde W, ten Kulve J, Woerdeman J, Kaufman JM, de Jong FH. Effects of oestradiol on gonadotrophin levels in normal and castrated men. Clin Endocrinol (Oxf). 2009;71:874–879.
50. Eisenegger C, von Eckardstein A, Fehr E, von Eckardstein S. Pharmacokinetics of testosterone and estradiol gel preparations in healthy young men. Psychoneuroendocrinology. 2013;38:171–178.
51. WPATH Standards of Care Version 7. https://www.wpath.org/publications/soc. Accessed 25 January 2020.
52. Armuand G, Dhejne C, Olofsson JI, Rodriguez-Wallberg KA. Transgender men's experiences of fertility preservation: a qualitative study. Hum Reprod. 2017;32:383-390.