Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Gender dysphoria in children and adolescents: an overview

Abstract

Over the last decade, we have witnessed considerable progress in gender dysphoria (GD) terminology in an attempt to better describe the condition based on certain criteria. The ever-increasing social acceptance and destigmatization of children and adolescents with GD have resulted in an increased number of transgender individuals seeking endocrine care. In addition to terminology and diagnostic criteria, the tremendous progress of genetics and neuroimaging has enabled us to have a deeper understanding of the complex pathogenesis of GD. Although helpful guidelines for treatment with GnRH analogs and gender-affirming hormones have been proposed, several challenges and controversies still exist. In this article, the current knowledge about GD in adolescents is reviewed, with particular emphasis on terminology, clinical manifestations, and epidemiologic data. The neurobiological basis of the condition is presented, and both hormonal treatment and mental issues of transgender individuals are discussed. Undoubtedly, further research will optimize the diagnostic and therapeutic approach of children and adolescents with GD.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    World Health Organization (2018) International statistical classification of diseases and related health problems (11th revision)

  2. 2.

    Unger CA (2014) Care of the transgender patient: the role of the gynecologist. Am J Obstet Gynecol 210(1):16–26

  3. 3.

    American Psychiatric Association (2013) The diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Publishing, Arlington

  4. 4.

    Martinerie L, Condat A, Bargiacchi A, Bremont-Weill C, de Vries MC, Hannema SE (2018) Management of endocrine disease: approach to the management of children and adolescents with gender Dysphoria. Eur J Endocrinol 179(5):R219–R237

  5. 5.

    T'Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V (2019) Endocrinology of transgender medicine. Endocr Rev 40(1):97–117

  6. 6.

    Atkinson SR, Russell D. Gender dysphoria. FOCUS 792 REPRINTED FROM AFP (Vol. 44). 2015. Retrieved from http://genderrights.org.au/sites/default/files/u9/AGAInfoPack2014.pdf

  7. 7.

    Ristori J, Steensma TD (2016) Gender dysphoria in childhood. Int Rev Psychiatry 28(1):13–20

  8. 8.

    Cohen-Kettenis PT, Owen A, Kaijser VG, Bradley SJ, Zucker KJ (2003) Demographic characteristics, social competence, and behavior problems in children with gender identity disorder: a cross-national, cross-clinic comparative analysis. J Abnorm Child Psychol 31(1):41–53

  9. 9.

    Steensma TD, Zucker KJ, Kreukels BPC, VanderLaan DP, Wood H, Fuentes A, Cohen-Kettenis PT (2014) 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 42(4):635–647

  10. 10.

    Shumer DE, Nokoff NJ, Spack NP (2016) Advances in the care of transgender children and adolescents. Adv Pediatr Infect Dis 63(1):79–102

  11. 11.

    Drummond KD, Bradley SJ, Peterson-Badali M, Zucker KJ (2008) A follow-up study of girls with gender identity disorder. Dev Psychol 44:34–45

  12. 12.

    Wallien MSC, Quilty LC, Steensma TD, Singh D, Lambert SL, Leroux A et al (2009) Cross-national replication of the gender identity interview for children. J Pers Assess 91:545–552

  13. 13.

    Steensma TD, Biemond R, de Boer F, Cohen-Kettenis PT (2011) Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. Clin Child Psychol Psychiatry 16:499–516

  14. 14.

    Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH et al (2017) Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 102:3869–3903

  15. 15.

    Steensma TD, Kreukels BPC, de Vries ALC, Cohen-Kettenis PT (2013) Gender identity development in adolescence. Horm Behav 64:288–297

  16. 16.

    Littman L (2018) Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria. PLoS One 13(8):e0202330

  17. 17.

    Zucker KJ (2019) Adolescents with gender dysphoria: reflections on some contemporary clinical and research issues. Arch Sex Behav

  18. 18.

    Brandelli CA (2019) Formal comment on: parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria. PLoS One 14(3):e0212578

  19. 19.

    Restar AJ, Methodological Critique of Littman's (2018) Parental-respondents accounts of "rapid-onset gender dysphoria". Arch Sex Behav 2019

  20. 20.

    Hutchinson A, Midgen M & Spiliadis A. In support of research into rapid-onset gender dysphoria. Arch Sex Behav. 2019

  21. 21.

    Shields JP, Cohen R, Glassman JR, Whitaker K, Franks H, Bertolini I (2013) Estimating population size and demographic characteristics of lesbian, gay, bisexual, and transgender youth in middle school. J Adolesc Health 52:248–250

  22. 22.

    Clark TC, Lucassen MFG, Bullen P, Denny SJ, Fleming TM, Robinson EM, Rossen FV (2014) The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12). J Adolesc Health 55:93–99

  23. 23.

    Eisenberg ME, Gower AL, McMorris BJ, Rider G, Shea G, Coleman E (2017) Risk and protective factors in the lives of transgender/gender nonconforming adolescents. J Adolesc Health 61:521–526

  24. 24.

    Zucker KJ (2017) Epidemiology of gender dysphoria and transgender identity. Sex Health 14(5):404

  25. 25.

    de Graaf NM, Giovanardi G, Zitz C, Carmichael P (2018) Sex ratio in children and adolescents referred to the gender identity development services in the UK (2009–2016) [letter to the editor]. Arch Sex Behav 47:1301–1304

  26. 26.

    Skordis N, Butler G, de Vries MC, Main K, Hannema SE (2018) ESPE and PES international survey of centers and clinicians delivering specialist care for children and adolescents with gender dysphoria. Horm Res Paediatr 90(5):326–331

  27. 27.

    Butler G, De Graaf N, Wren B, Carmichael P (2018) Assessment and support of children and adolescents with gender dysphoria. Arch Dis Child 103(7):631–636

  28. 28.

    Fielding J, Bass C (2018) Individuals seeking gender reassignment: marked increase in demand for services. BJPsych Bull 42(5):206–210

  29. 29.

    Aitken M, Steensma TD, Blanchard R, VanderLaan DP, Wood H, Fuentes A et al (2015) Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. J Sex Med 12(3):756–763

  30. 30.

    Sumia M, Lindberg N, Työläjärvi M, Kaltiala-Heino R (2017) Current and recalled childhood gender identity in community youth in comparison to referred adolescents seeking sex reassignment. J Adolesc Health 56:34–39

  31. 31.

    Levitan N, Barkmann C, Richter-Appelt H, Schulte-Markwort M, Becker-Hebly I (2019) Risk factors for psychological functioning in German adolescents with gender dysphoria: poor peer relations and general family functioning. Eur Child Adolesc Psychiatry

  32. 32.

    Saleem F, Rizvi SW (2017) Transgender associations and possible etiology: a literature review. Cureus. 9(12):e1984

  33. 33.

    Garcia-Falgueras A, Swaab DF (2008) A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain. 131(12):3132–3146

  34. 34.

    Rosenthal SM (2014) Approach to the patient: transgender youth: endocrine considerations. J Clin Endocrinol Metab 99(12):4379–4389

  35. 35.

    Zhou J-N, Hofman MA, Gooren LJG, Swaab DF (1995) A sex difference in the human brain and its relation to transsexuality. Nature. 378(6552):68–70

  36. 36.

    Kruijver FPM, Zhou J-N, Pool CW, Hofman MA, Gooren LJG, Swaab DF (2000) Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 85(5):2034–2041

  37. 37.

    Taziaux M, Staphorsius AS, Ghatei MA, Bloom SR, Swaab DF, Bakker J (2016) Kisspeptin expression in the human Infundibular nucleus in relation to sex, gender identity, and sexual orientation. J Clin Endocrinol Metab 101(6):2380–2389

  38. 38.

    Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E (2009) Regional gray matter variation in male-to-female transsexualism. NeuroImage. 46(4):904–907

  39. 39.

    Berglund H, Lindstrom P, Dhejne-Helmy C, Savic I (2008) Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex 18(8):1900–1908

  40. 40.

    Savic I, Arver S (2011) Sex dimorphism of the brain in male-to-female transsexuals. Cereb Cortex 21(11):2525–2533

  41. 41.

    Nota NM, Burke SM, den Heijer M, Soleman RS, Lambalk CB, Cohen-Kettenis PT et al (2017) Brain sexual differentiation and effects of cross-sex hormone therapy in transpeople: a resting-state functional magnetic resonance study. Neurophysiol Clin 47(5–6):361–370

  42. 42.

    Nota NM, Kreukels BPC, den Heijer M, Veltman DJ, Cohen-Kettenis PT, Burke SM, Bakker J (2017) Brain functional connectivity patterns in children and adolescents with gender dysphoria: sex-atypical or not? Psychoneuroendocrinology. 86:187–195

  43. 43.

    Schöning S, Engelien A, Bauer C, Kugel H, Kersting A, Roestel C et al (2010) Original research —intersex and gender identity disorders : neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. J Sex Med 7(5):1858–1867

  44. 44.

    Green R (2000) Family cooccurrence of “gender dysphoria”: ten sibling or parent–child pairs. Arch Sex Behav 29(5):499–507

  45. 45.

    Gómez-Gil E, Esteva I, Almaraz MC, Pasaro E, Segovia S, Guillamon A (2010) Familiality of gender identity disorder in non-twin siblings. Arch Sex Behav 39:546–552

  46. 46.

    van Beijsterveldt CEM, Hudziak JJ, Boomsma DI (2006) Genetic and environmental influences on cross-gender behavior and relation to behavior problems: a study of Dutch twins at ages 7 and 10 years. Arch Sex Behav 35:647–658

  47. 47.

    Heylens G, De Cuypere G, Zucker KJ, Schelfaut C, Elaut E, Vanden Bossche H et al (2012) Gender identity disorder in twins: a review of the case report literature. J Sex Med 9(3):751–757

  48. 48.

    Inoubli A, De Cuypere G, Rubens R, Heylens G, Elaut E, Van Caenegem E, Menten B, T’Sjoen G (2011) Karyotyping, is it worthwhile in transsexualism? J Sex Med 8:475–478

  49. 49.

    Pang KC, Feldman D, Oertel R, Telfer M (2018) Molecular karyotyping in children and adolescents with gender dysphoria. Transgender Health 3(1):147–153

  50. 50.

    Fernández R, Guillamón A, Gómez-Gil E, Esteva I, Almaraz MC, Cortés-Cortés J et al (2018) Analyses of karyotype by G-banding and high-resolution microarrays in a gender dysphoria population. Genes Genom 40(5):465–473

  51. 51.

    Henningsson S, Westberg L, Nilsson S, Lundström B, Ekselius L, Bodlund O et al (2005) Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology. 30(7):657–664

  52. 52.

    Cooke B, Hegstrom CD, Villeneuve LS, Breedlove SM (1998) Sexual differentiation of the vertebrate brain: principles and mechanisms. Front Neuroendocrinol 19(4):323–362

  53. 53.

    Wilson JD (1999) The role of androgens in male gender role behavior. Endocr Rev 20(5):726–737

  54. 54.

    Hare L, Bernard P, Sánchez FJ, Baird PN, Vilain E, Kennedy T et al (2009) Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol Psychiatry 65(1):93–96

  55. 55.

    Kazemi-Esfarjani P, Trifiro MA, Pinsky L (1995) Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet 4(4):523–527

  56. 56.

    Pol HEH, Cohen-Kettenis PT, Van Haren NEM, Peper JS, Brans RGH, Cahn W et al (2006) Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure. Eur J Endocrinol 155(suppl_1):S107–S114

  57. 57.

    Ujike H, Otani K, Nakatsuka M, Ishii K, Sasaki A, Oishi T et al (2009) Association study of gender identity disorder and sex hormone-related genes. Prog Neuro-Psychopharmacol Biol Psychiatry 33(7):1241–1244

  58. 58.

    Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E et al (2014) Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. J Sex Med 11(12):2986–2994

  59. 59.

    Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E et al (2014) The (CA)n polymorphism of ERβ gene is associated with FtM transsexualism. J Sex Med 11(3):720–728

  60. 60.

    Fernández R, Guillamon A, Cortés-Cortés J, Gómez-Gil E, Jácome A, Esteva I et al (2018) Molecular basis of gender dysphoria: androgen and estrogen receptor interaction. Psychoneuroendocrinology. 98:161–167

  61. 61.

    Foreman M, Hare L, York K, Balakrishnan K, Sánchez FJ, Harte F et al (2019) Genetic link between gender dysphoria and sex hormone signaling. J Clin Endocrinol Metab 104(2):390–396

  62. 62.

    Yang F, Zhu XH, Zhang Q, Sun NX, Ji YX, Ma JZ et al (2017) Genomic characteristics of gender Dysphoria patients and identification of rare mutations in RYR3 gene. Sci Rep 7(1):8339

  63. 63.

    Rivas MP, Moreira LMA, Santo LDE, Marques ACSS, El-Hani CN, Toralles MBP (2014) New studies of second and fourth digit ratio as a morphogenetic trait in subjects with congenital adrenal hyperplasia. Am J Hum Biol 26(4):559–561. https://doi.org/10.1002/ajhb.22545

  64. 64.

    Wallien MSC, Zucker KJ, Steensma TD, Cohen-Kettenis PT (2008) 2D:4D finger-length ratios in children and adults with gender identity disorder. Horm Behav 54(3):450–454

  65. 65.

    Kraemer B, Noll T, Delsignore A, Milos G, Schnyder U, Hepp U (2009) Finger length ratio (2D:4D) in adults with gender identity disorder. Arch Sex Behav 38(3):359–363

  66. 66.

    Wallien MSC, Cohen-Kettenis PT (2008) Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry 47(12):1413–1423

  67. 67.

    Carel JC, Léger J (2008) Clinical practice. Precocious puberty. N Engl J Med 358:2366–2377

  68. 68.

    Costa R, Carmichael P, Colizzi M (2016) To treat or not to treat: puberty suppression in childhood-onset gender dysphoria. Nat Rev Urol 13(8):456–462

  69. 69.

    de Vries AL, Klink D, Cohen-Kettenis PT (2016) What the primary care pediatrician needs to know about gender incongruence and gender dysphoria in children and adolescents. Pediatr Clin N Am 63(6):1121–1135

  70. 70.

    Kaltiala-Heino R, Bergman H, Työläjärvi M, Frisén L (2018) Gender dysphoria in adolescence: current perspectives. Adolesc Health Med Ther 9:31–41

  71. 71.

    Rafferty J, COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH; COMMITTEE ON ADOLESCENCE; SECTION ON LESBIAN, GAY, BISEXUAL, AND TRANSGENDER HEALTH AND WELLNESS (2018) Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents. Pediatrics 142(4):e20182162

  72. 72.

    Panagiotakopoulos L (2018) Transgender medicine - puberty suppression. Rev Endocr Metab Dis 19(3):221–225

  73. 73.

    Butler G, Wren B, Carmichael P (2019) Puberty blocking in gender dysphoria: suitable for all? Arch Dis Child 104(6):509–510

  74. 74.

    Schagen SEE, Cohen-Kettenis PT, Delemarre-van de Waal HA, Hannema SE (2016) Efficacy and safety of gonadotropin-releasing hormone agonist treatment to suppress puberty in gender dysphoric adolescents. J Sex Med 13:1125–1132

  75. 75.

    Badaru A, Wilson DM, Bachrach LK, Fechner P, Gandrud LM, Durham E et al (2006) Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty. J Clin Endocrinol Metab 91:1862–1867

  76. 76.

    Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, ESPE-LWPES GnRH Analogs Consensus Conference Group et al (2009) Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 123:e752–e762

  77. 77.

    Lee JW, Kim HJ, Choe YM, Kang HS, Kim SK, Jun YH et al (2014) 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 19(3):135–140

  78. 78.

    Hess J, Rossi Neto R, Panic L, Rübben H, Senf W (2014) Satisfaction with male-to-female gender reassignment surgery. Dtsch Arztebl Int 111(47):795–801

  79. 79.

    Clements-Nolle K, Marx R, Katz M (2006) Attempted suicide among transgender persons: the influence of gender-based discrimination and victimization. J Homosex 51(3):53–69

  80. 80.

    Almeida J, Johnson RM, Corliss HL, Molnar BE, Azrael D (2009) Emotional distress among LGBT youth: the influence of perceived discrimination based on sexual orientation. J Youth Adolesc 38(7):1001–1014

  81. 81.

    Haas AP, Eliason M, Mays VM, Mathy RM, Cochran SD, D'Augelli AR et al (2011) Suicide and suicide risk in lesbian, gay, bisexual, and transgender populations: review and recommendations. J Homosex 58(1):10–51

  82. 82.

    Colizzi M, Costa R, Todarello O (2014) Transsexual patients’ psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: results from a longitudinal study. Psychoneuroendocrinology. 39:65–73

  83. 83.

    Connolly MD, Zervos MJ, Barone CJ II, Johnson CC, Joseph CL (2016) The mental health of transgender youth: advances in understanding. J Adolesc Health 59(5):489–495

  84. 84.

    Edwards-Leeper L, Spack NP (2012) Psychological evaluation and medical treatment of transgender youth in an interdisciplinary “gender management service” (GeMS) in a major pediatric center. J Homosex 59(3):321–336

  85. 85.

    Lopez X, Stewart S, Jacobson-Dickman E (2016) (2016). Approach to children and adolescents with gender dysphoria. Pediatr Rev 37(3):89–98

  86. 86.

    Colizzi M, Costa R, Todarello O (2015) (2015). Dissociative symptoms in individuals with gender dysphoria: is the elevated prevalence real? Psychiatry Res 226(1):173–180

  87. 87.

    Hidalgo MA, Ehrensaft D, Tishelman AC, Clark LF, Garofalo R, Rosenthal SM et al (2013) The gender affirmative model: what we know and what we aim to learn. Hum Dev. 56(5):285–290

  88. 88.

    Condat A, Mendes N, Drouineaud V, Gründler N, Lagrange C, Chiland C, Wolf JP, Ansermet F, Cohen D (2018) Biotechnologies that empower transgender persons to self-actualize as individuals, partners, spouses and parents are defining new ways to conceive a child: psychological considerations and ethical issues. Philos Ethics Humanit Med 13(1):1

Download references

Author information

Correspondence to Nicos Skordis.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Skordis, N., Kyriakou, A., Dror, S. et al. Gender dysphoria in children and adolescents: an overview. Hormones (2020). https://doi.org/10.1007/s42000-020-00174-1

Download citation

Keywords

  • Gender dysphoria
  • Adolescents
  • Genetics
  • Cross-hormone treatment