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Psychosocial challenges and hormonal treatment in gender diverse children and adolescents. A narrative review

Abstract

Gender dysphoria (GD) in children and adolescents is a condition that is characterized by an incongruence between the assigned and experienced gender. Despite the diversity in clinical presentation, literature demonstrates that GD might lead to poor mental health and high rates of co-occurring psychopathology. Due to the overlap of physical aspects as well as psychological needs in these children, a multidisciplinary approach is highly desirable. The aim of this narrative review is to give an overview of recent literature on several topics relevant in this domain. Guidelines on psychological counseling and hormonal treatment are given and challenging topics subject to controversy are explained. Furthermore, attention is drawn to the risks and protective factors in psychological functioning, including the growing evidence of a frequent co-occurrence with Autism Spectrum Disorder. Finally the psycho-sexual development in these children, the impact on fertility and fertility preservation are discussed.

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Fig. 1: DSM-5 criteria gender dysphoria in childhood [2].
Fig. 2: Hormonal treatment in children/adolescents with confirmed GD.
Fig. 3: Initial guidelines for co-occurring ASD and GD in adolescents [65].

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References

  1. Alberse AE, de Vries AL, Elzinga WS, Steensma TD. Self-perception of transgender clinic referred gender diverse children and adolescents. Clin Child Psychol Psychiatry. 2019;24:388–401.

    PubMed  PubMed Central  Google Scholar 

  2. Association AP. Diagnostic and statistical manual of mental disorders (5th ed.). 2013.

  3. Beek TF, Cohen-Kettenis PT, Bouman WP, de Vries AL, Steensma TD, Witcomb GL, et al. Gender incongruence of childhood: clinical utility and stakeholder agreement with the World Health Organization’s proposed ICD-11 criteria. PLoS ONE 2017;12:e0168522.

    PubMed  PubMed Central  Google Scholar 

  4. Steensma TD, Cohen-Kettenis PT, Zucker KJ. Evidence for a change in the sex ratio of children referred for gender dysphoria: data from the center of expertise on gender dysphoria in Amsterdam (1988-2016). J Sex Marital Ther. 2018;44:713–5.

    PubMed  Google Scholar 

  5. 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;12:756–63.

    PubMed  Google Scholar 

  6. de Graaf NM, Carmichael P, Steensma TD, Zucker KJ. Evidence for a change in the sex ratio of children referred for gender dysphoria: data from the gender identity development service in London (2000–2017). J Sex Med. 2018;15:1381–3.

    PubMed  Google Scholar 

  7. Hsieh S, Leininger J. Resource list: clinical care programs for gender-nonconforming children and adolescents. Pediatr Ann 2014;43:238–44.

    PubMed  Google Scholar 

  8. Kaltiala-Heino R, Sumia M, Tyolajarvi M, Lindberg N. Two years of gender identity service for minors: overrepresentation of natal girls with severe problems in adolescent development. Child Adolesc Psychiatry Ment Health. 2015;9:9.

    PubMed  PubMed Central  Google Scholar 

  9. Khatchadourian K, Amed S, Metzger DL. Clinical management of youth with gender dysphoria in Vancouver. J Pediatr 2014;164:906–11.

    CAS  PubMed  Google Scholar 

  10. Spack NP, Edwards-Leeper L, Feldman HA, Leibowitz S, Mandel F, Diamond DA, et al. Children and adolescents with gender identity disorder referred to a pediatric medical center. Pediatrics 2012;129:418–25.

    PubMed  Google Scholar 

  11. Rosenthal SM. Approach to the patient: transgender youth: endocrine considerations. J Clin Endocrinol Metab. 2014;99:4379–89.

    CAS  PubMed  Google Scholar 

  12. Sherer I, Rosenthal SM, Ehrensaft D, Baum J. Child and Adolescent Gender Center: a multidisciplinary collaboration to improve the lives of gender nonconforming children and teens. Pediatr Rev 2012;33:273–5.

    PubMed  Google Scholar 

  13. de Vries AL, Cohen-Kettenis PT. Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex. 2012;59:301–20.

    PubMed  Google Scholar 

  14. Zucker KJ, Bradley SJ, Owen-Anderson A, Kibblewhite SJ, Cantor JM. Is gender identity disorder in adolescents coming out of the closet? J Sex Marital Ther. 2008;34:287–90.

    PubMed  Google Scholar 

  15. Byne W, Bradley SJ, Coleman E, Eyler AE, Green R, Menvielle EJ, et al. Report of the American Psychiatric Association Task Force on treatment of gender identity disorder. Arch Sex Behav. 2012;41:759–96.

    PubMed  Google Scholar 

  16. Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, Version 7. Int J Transgenderism. 2012;13:165–232.

    Google Scholar 

  17. Adelson SL. Practice parameter on gay, lesbian, or bisexual sexual orientation, gender nonconformity, and gender discordance in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2012;51:957–74.

    PubMed  Google Scholar 

  18. Obedin-Maliver J, Goldsmith ES, Stewart L, White W, Tran E, Brenman S, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. JAMA 2011;306:971–7.

    CAS  PubMed  Google Scholar 

  19. Association A. Guidelines for psychological practice with transgender and gender nonconforming people. Am Psychologist 2015;70:832–64.

    Google Scholar 

  20. 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. Endocr Pract 2017;23:1437.

    PubMed  Google Scholar 

  21. de Vries AL, 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.

    PubMed  Google Scholar 

  22. Drescher J. Controversies in gender diagnoses. LGBT Health. 2014;1:10–4.

    PubMed  Google Scholar 

  23. 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.

    PubMed  Google Scholar 

  24. Cohen-Kettenis PT, van Goozen SH. Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur Child Adolesc Psychiatry. 1998;7:246–8.

    CAS  PubMed  Google Scholar 

  25. Delamarre-van der 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;155:131–7.

    Google Scholar 

  26. Boepple PA, Mansfield MJ, Wierman ME, Rudlin CR, Bode HH, Crigler JF Jr., et al. Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty. Endocr Rev 1986;7:24–33.

    CAS  PubMed  Google Scholar 

  27. Tack LJ, Craen M, Dhondt K, Vanden Bossche 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.

    PubMed  PubMed Central  Google Scholar 

  28. Tack LJW, Craen M, Lapauw B, Goemaere S, Toye K, Kaufman JM, et al. Proandrogenic and antiandrogenic progestins in transgender youth: differential effects on body composition and bone metabolism. J Clin Endocrinol Metab. 2018;103:2147–56.

    PubMed  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. Kreukels BP, Guillamon A. Neuroimaging studies in people with gender incongruence. Int Rev Psychiatry. 2016;28:120–8.

    PubMed  Google Scholar 

  31. Hulshoff Pol H, Cohen-Kettenis P, Haren NEM, Peper J, Brans R, Cahn W, et al. Changing your sex changes your brain: Influences of testosterone and estrogen on adult human brain structure. Eur J Endocrinol. 2006;155:107–14.

    Google Scholar 

  32. Zubiaurre-Elorza L, Junque C, Gomez-Gil E, Segovia S, Carrillo B, Rametti G, et al. Cortical thickness in untreated transsexuals. Cereb Cortex. 2013;23:2855–62.

    PubMed  Google Scholar 

  33. Rametti G, Carrillo B, Gomez-Gil E, Junque C, Zubiaurre-Elorza L, Segovia S, et al. Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study. Psychoneuroendocrinology. 2012;37:1261–9.

    CAS  PubMed  Google Scholar 

  34. Jarin J, Pine-Twaddell E, Trotman G, Stevens J, Conard LA, Tefera E, et al. Cross-sex hormones and metabolic parameters in adolescents with gender dysphoria. Pediatrics. 2017;139:e20163173. https://doi.org/10.1542/peds.2016-3173.

  35. Iwamoto SJ, Defreyne J, Rothman MS, Van Schuylenbergh J, Van de Bruaene L, Motmans J, et al. Health considerations for transgender women and remaining unknowns: a narrative review. Ther Adv Endocrinol Metab. 2019;10:2042018819871166.

    PubMed  PubMed Central  Google Scholar 

  36. Defreyne J, Van de Bruaene LDL, Rietzschel E, Van Schuylenbergh J, T’Sjoen GGR. Effects of gender-affirming hormones on lipid, metabolic, and cardiac surrogate blood markers in transgender persons. Clin Chem. 2019;65:119–34.

    CAS  PubMed  Google Scholar 

  37. Ikeda K, Baba T, Noguchi H, Nagasawa K, Endo T, Kiya T, et al. Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology. Hum Reprod. 2013;28:453–61.

    CAS  PubMed  Google Scholar 

  38. Baba T, Endo T, Honnma H, Kitajima Y, Hayashi T, Ikeda H, et al. Association between polycystic ovary syndrome and female-to-male transsexuality. Hum Reprod. 2007;22:1011–6.

    PubMed  Google Scholar 

  39. De Roo C, Tilleman K, Vercruysse C, Declercq H, T’Sjoen G, Weyers S, et al. Texture profile analysis reveals a stiffer ovarian cortex after testosterone therapy: a pilot study. J Assist Reprod Genet. 2019;36:1837–43.

    PubMed  PubMed Central  Google Scholar 

  40. de Vries ALC, Steensma TD, Doreleijers TAH, Cohen-Kettenis PT. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med. 2011;8:2276–83.

    PubMed  Google Scholar 

  41. Steensma TD, Zucker KJ, Kreukels BPC, Vanderlaan DP, Wood H, Fuentes A, et al. 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 Psychol. 2014;42:635–47.

    PubMed  Google Scholar 

  42. 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 Psychol. 2003;31:41–53.

    PubMed  Google Scholar 

  43. de Vries ALC, Doreleijers TAH, Steensma TD, Cohen-Kettenis PT. Psychiatric comorbidity in gender dysphoric adolescents. J Child Psychol Psychiatry. 2011;52:1195–202.

    PubMed  Google Scholar 

  44. Wallien MSC, Swaab H, Cohen-Kettenis PT. Psychiatric comorbidity among children with gender identity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:1307–14.

    PubMed  Google Scholar 

  45. Veale JF, Watson RJ, Peter T, Saewyc EM. Mental health disparities among Canadian transgender youth. J Adolesc Health. 2017;60:44–9.

    PubMed  PubMed Central  Google Scholar 

  46. Reisner SL, Vetters R, Leclerc M, Zaslow S, Wolfrum S, Shumer D, et al. Mental health of transgender youth in care at an adolescent urban community health center: a matched retrospective cohort study. J Adolesc Health. 2015;56:274–9.

    PubMed  PubMed Central  Google Scholar 

  47. Carter B, McCloskey L A. LM. Peers and the maintenance of sex-typed behavior: the development of children’s conceptions of cross-gender behavior in their peers. Soc Cogn. 1984;2:294–314.

    Google Scholar 

  48. Levy GD, Taylor MG, Gelman SA. Traditional and evaluative aspects of flexibility in gender roles, social conventions, moral rules, and physical laws. Child Dev. 1995;66:515–31.

    CAS  PubMed  Google Scholar 

  49. Liben LS, Signorella ML. Gender-schematic processing in children: the role of initial interpretations of stimuli. Dev Psychol. 1993;29:141–9.

    Google Scholar 

  50. Stoddart T, Turiel E. Children’s concepts of cross-gender activities. Blackwell Publishing; 1985. p. 1241–52.

  51. de Vries AL, Steensma TD, Cohen-Kettenis PT, VanderLaan DP, Zucker KJ. Poor peer relations predict parent- and self-reported behavioral and emotional problems of adolescents with gender dysphoria: a cross-national, cross-clinic comparative analysis. Eur Child Adolesc Psychiatry. 2016;25:579–88.

    PubMed  Google Scholar 

  52. de Graaf NM, Cohen-Kettenis PT, Carmichael P, de Vries ALC, Dhondt K, Laridaen J, et al. Psychological functioning in adolescents referred to specialist gender identity clinics across Europe: a clinical comparison study between four clinics. Eur Child Adolesc Psychiatry. 2018;27:909–19.

    PubMed  Google Scholar 

  53. de Vries AL, Noens IL, Cohen-Kettenis PT, van Berckelaer-Onnes IA, Doreleijers TA. Autism spectrum disorders in gender dysphoric children and adolescents. J Autism Dev Disord. 2010;40:930–6.

    PubMed  PubMed Central  Google Scholar 

  54. Skagerberg E, Di Ceglie D, Carmichael P. Brief report: autistic features in children and adolescents with gender dysphoria. J Autism Dev Disord. 2015;45:2628–32.

    PubMed  Google Scholar 

  55. Strang JF, Kenworthy L, Dominska A, Sokoloff J, Kenealy LE, Berl M, et al. Increased gender variance in autism spectrum disorders and attention deficit hyperactivity disorder. Arch Sex Behav. 2014;43:1525–33.

    PubMed  Google Scholar 

  56. Janssen A, Huang H, Duncan C. Gender variance among youth with autism spectrum disorders: a retrospective chart review. Transgend Health 2016;1:63–8.

    PubMed  PubMed Central  Google Scholar 

  57. May T, Pang K, Williams KJ. Gender variance in children and adolescents with autism spectrum disorder from the National Database for Autism Research. Int J Transgenderism. 2017;18:7–15.

    Google Scholar 

  58. van der Miesen AIR, de Vries ALC, Steensma TD, Hartman CA. Autistic symptoms in children and adolescents with gender dysphoria. J Autism Dev Disord. 2018;48:1537–48.

    PubMed  Google Scholar 

  59. Nabbijohn AN, van der Miesen AIR, Santarossa A, Peragine D, de Vries ALC, Popma A, et al. Gender variance and the autism spectrum: an examination of children ages 6-12 years. J Autism Dev Disord. 2019;49:1570–85.

    PubMed  Google Scholar 

  60. Turban JL, van Schalkwyk GI. “Gender Dysphoria” and autism spectrum disorder: is the link real? J Am Acad Child Adolesc Psychiatry. 2018;57:8–9.e2.

    PubMed  Google Scholar 

  61. van der Miesen AIR, Cohen-Kettenis PT, de Vries ALC. Is there a link between gender dysphoria and autism spectrum disorder? J Am Acad Child Adolesc Psychiatry. 2018;57:884–5.

    PubMed  Google Scholar 

  62. Strang JF, Janssen A, Tishelman A, Leibowitz SF, Kenworthy L, McGuire JK, et al. Revisiting the link: evidence of the rates of autism in studies of gender diverse individuals. J Am Acad Child Adolesc Psychiatry. 2018;57:885–7.

    PubMed  Google Scholar 

  63. Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002;6:248–54.

    PubMed  Google Scholar 

  64. Parkinson J. Gender dysphoria in Asperger’s syndrome: a caution. Australas Psychiatry 2014;22:84–5.

    PubMed  Google Scholar 

  65. Strang JF, Meagher H, Kenworthy L, de Vries ALC, Menvielle E, Leibowitz S, et al. Initial clinical guidelines for co-occurring autism spectrum disorder and gender dysphoria or incongruence in adolescents. J Clin Child Adolesc Psychol. 2018;47:105–15.

    PubMed  Google Scholar 

  66. Pache TD, Chadha S, Gooren LJ, Hop WC, Jaarsma KW, Dommerholt HB, et al. Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome? Histopathology 1991;19:445–52.

    CAS  PubMed  Google Scholar 

  67. Schulze C. Response of the human testis to long-term estrogen treatment: morphology of Sertoli cells, Leydig cells and spermatogonial stem cells. Cell Tissue Res. 1988;251:31–43.

    CAS  PubMed  Google Scholar 

  68. Finlayson C, Johnson EK, Chen D, Dabrowski E, Gosiengfiao Y, Campo-Engelstein L, et al. Proceedings of the working group session on fertility preservation for individuals with gender and sex diversity. Transgend Health 2016;1:99–107.

    PubMed  PubMed Central  Google Scholar 

  69. Johnson EK, Finlayson C. Preservation of fertility potential for gender and sex diverse individuals. Transgend Health 2016;1:41–4.

    PubMed  PubMed Central  Google Scholar 

  70. Hagen CP, Sorensen K, Anderson RA, Juul A. Serum levels of antimullerian hormone in early maturing girls before, during, and after suppression with GnRH agonist. Fertil Steril 2012;98:1326–30.

    CAS  PubMed  Google Scholar 

  71. Grynberg M, Fanchin R, Dubost G, Colau JC, Bremont-Weil C, Frydman R, et al. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod Biomed Online. 2010;20:553–8.

    CAS  PubMed  Google Scholar 

  72. De Roo C, Lierman S, Tilleman K, Peynshaert K, Braeckmans K, Caanen M, et al. Ovarian tissue cryopreservation in female-to-male transgender people: insights into ovarian histology and physiology after prolonged androgen treatment. Reprod Biomed Online. 2017;34:557–66.

    PubMed  Google Scholar 

  73. Kent MA, Winoker JS, Grotas AB. Effects of feminizing hormones on sperm production and malignant changes: microscopic examination of post orchiectomy specimens in transwomen. Urology 2018;121:93–6.

    PubMed  Google Scholar 

  74. Schneider F, Kliesch S, Schlatt S, Neuhaus N. Andrology of male-to-female transsexuals: influence of cross-sex hormone therapy on testicular function. Andrology. 2017;5:873–80.

    CAS  PubMed  Google Scholar 

  75. Wyns C, Curaba M, Vanabelle B, Van Langendonckt A, Donnez J. Options for fertility preservation in prepubertal boys. Hum Reprod Update. 2010;16:312–28.

    PubMed  Google Scholar 

  76. Donnez J, Dolmans MM. Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;32:1167–70.

    PubMed  PubMed Central  Google Scholar 

  77. Chen D, Simons L, Johnson EK, Lockart BA, Finlayson C. Fertility preservation for transgender adolescents. J Adolesc Health. 2017;61:120–3.

    PubMed  PubMed Central  Google Scholar 

  78. Nahata L, Tishelman AC, Caltabellotta NM, Quinn GP. Low fertility preservation utilization among transgender youth. J Adolesc Health. 2017;61:40–4.

    PubMed  Google Scholar 

  79. Sutter P, Kira K, Verschoor A, Hotimsky A. The desire to have children and the preservation of fertility in transsexual women: A survey. Int J Transgend. 2002;6:215–21.

    Google Scholar 

  80. Wierckx K, Van Caenegem E, Pennings G, Elaut E, Dedecker D, Van de Peer F, et al. Reproductive wish in transsexual men. Hum Reprod 2012;27:483–7.

    PubMed  Google Scholar 

  81. Strang JF, Jarin J, Call D, Clark B, Wallace GL, Anthony LG, et al. Transgender youth fertility attitudes questionnaire: measure development in nonautistic and autistic transgender youth and their parents. J Adolesc Health. 2018;62:128–35.

    PubMed  Google Scholar 

  82. Wenzel L, Dogan-Ates A, Habbal R, Berkowitz R, Goldstein DP, Bernstein M, et al. Defining and measuring reproductive concerns of female cancer survivors. J Natl Cancer Inst Monogr. 2005;34:94–8.

    Google Scholar 

  83. Quinn GP, Murphy D, Wang H, Sawczyn KK, Knapp C. Having cancer does not change wanting a baby: healthy adolescent girls’ perceptions of cancer-related infertility. J Adolesc Health. 2013;52:164–9.

    PubMed  Google Scholar 

  84. Meneses K, McNees P, Azuero A, Jukkala A. Development of the fertility and cancer project: an internet approach to help young cancer survivors. Oncol Nurs Forum. 2010;37:191–7.

    PubMed  Google Scholar 

  85. Bungener SL, Steensma TD, Cohen-Kettenis PT, de Vries ALC. Sexual and romantic experiences of transgender youth before gender-affirmative treatment. Pediatrics. 2017;139:e20162283. https://doi.org/10.1542/peds.2016-2283.

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Baetens, L., Dhondt, K. Psychosocial challenges and hormonal treatment in gender diverse children and adolescents. A narrative review. Int J Impot Res 33, 217–227 (2021). https://doi.org/10.1038/s41443-020-0291-z

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