Ann Pediatr Endocrinol Metab.  2016 Dec;21(4):185-192. 10.6065/apem.2016.21.4.185.

Transgender youth: current concepts

• Rosenthal

• KMID: 2366808
• DOI: http://doi.org/10.6065/apem.2016.21.4.185

Abstract

In many countries throughout the world, increasing numbers of gender nonconforming/transgender youth are seeking medical services to enable the development of physical characteristics consistent with their experienced gender. Such medical services include use of agents to block endogenous puberty at Tanner stage II with subsequent use of cross-sex hormones, and are based on longitudinal studies demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and continue to meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. This review addresses terms and definitions applicable to gender nonconforming youth, studies that shed light on the biologic determinants of gender identity, current clinical practice guidelines for transgender youth, challenges to optimal care, and priorities for research.

Keyword

Transgender; Gender nonconforming; Gender dysphoria; Gonadotropin releasing hormone agonist; Cross-sex hormones

Reference

1. Vance SR Jr, Ehrensaft D, Rosenthal SM. Psychological and medical care of gender nonconforming youth. Pediatrics. 2014; 134:1184–1192. PMID: 25404716.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington (VA): American Psychiatric Association Publishing;2013.

3. 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 Transgend. 2012; 13:165–232.

4. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ 3rd, Spack NP, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009; 94:3132–3154. PMID: 19509099.

5. Meyer-Bahlburg HF. Sex steroids and variants of gender identity. Endocrinol Metab Clin North Am. 2013; 42:435–452. PMID: 24011879.

6. Sherer I, Baum J, Ehrensaft D, Rosenthal SM. Affirming gender: caring for gender atypical children and adolescents. Contemp Pediatr. 2015; 32:16–19.

7. Drummond KD, Bradley SJ, Peterson-Badali M, Zucker KJ. A follow-up study of girls with gender identity disorder. Dev Psychol. 2008; 44:34–45. PMID: 18194003.

8. Wallien MS, Cohen-Kettenis PT. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry. 2008; 47:1413–1423. PMID: 18981931.

9. 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; 34:287–290. PMID: 18576228.

10. de Vries AL, Cohen-Kettenis PT. Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex. 2012; 59:301–320. PMID: 22455322.

11. 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; 129:418–425. PMID: 22351896.

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; 33:273–275. PMID: 22659258.

13. Conron KJ, Scott G, Stowell GS, Landers SJ. Transgender health in Massachusetts: results from a household probability sample of adults. Am J Public Health. 2012; 102:118–122. PMID: 22095354.

14. 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; 56:274–279. PMID: 25577670.

15. Travers R, Bauer G, Pyne J, Bradley K; for the Trans PULSE Project, Gale L, et al. Impacts of strong parental support for trans youth: a report prepared for Children’S Aid Society of Toronto and Delisle Youth Services. Trans Pulse. 2012; 10. 02.

16. Rosenthal SM. Approach to the patient: transgender youth: endocrine considerations. J Clin Endocrinol Metab. 2014; 99:4379–4389. PMID: 25140398.

17. Berenbaum SA, Bailey JM. Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2003; 88:1102–1106. PMID: 12629091.

18. Dessens AB, Slijper FM, Drop SL. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav. 2005; 34:389–397. PMID: 16010462.

19. Meyer-Bahlburg HF, Dolezal C, Baker SW, Ehrhardt AA, New MI. Gender development in women with congenital adrenal hyperplasia as a function of disorder severity. Arch Sex Behav. 2006; 35:667–684. PMID: 16902816.

20. Frisén L, Nordenström A, Falhammar H, Filipsson H, Holmdahl G, Janson PO, et al. Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency. J Clin Endocrinol Metab. 2009; 94:3432–3439. PMID: 19567521.

21. Meyer-Bahlburg HF, Dolezal C, Baker SW, New MI. Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav. 2008; 37:85–99. PMID: 18157628.

22. Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005; 34:399–410. PMID: 16010463.

23. Imperato-McGinley J, Peterson RE, Gautier T, Sturla E. Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency. N Engl J Med. 1979; 300:1233–1237. PMID: 431680.

24. Rösler A, Silverstein S, Abeliovich D. A (R80Q) mutation in 17 beta-hydroxysteroid dehydrogenase type 3 gene among Arabs of Israel is associated with pseudohermaphroditism in males and normal asymptomatic females. J Clin Endocrinol Metab. 1996; 81:1827–1831. PMID: 8626842.

25. Reiner WG, Gearhart JP. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. N Engl J Med. 2004; 350:333–341. PMID: 14736925.

26. Meyer-Bahlburg HF. Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav. 2005; 34:423–438. PMID: 16010465.

27. T'Sjoen G, De Cuypere G, Monstrey S, Hoebeke P, Freedman FK, Appari M, et al. Male gender identity in complete androgen insensitivity syndrome. Arch Sex Behav. 2011; 40:635–638. PMID: 20358272.

28. Hyde C, Kenna JC. A male MZ twin pair, concordant for transsexualism, discordant for schizophrenia. Acta Psychiatr Scand. 1977; 56:265–275. PMID: 562589.

29. Green R. Family cooccurrence of "gender dysphoria": ten sibling or parent-child pairs. Arch Sex Behav. 2000; 29:499–507. PMID: 10983252.

30. Coolidge FL, Thede LL, Young SE. The heritability of gender identity disorder in a child and adolescent twin sample. Behav Genet. 2002; 32:251–257. PMID: 12211624.

31. Heylens G, De Cuypere G, Zucker KJ, Schelfaut C, Elaut E, Vanden Bossche H, et al. Gender identity disorder in twins: a review of the case report literature. J Sex Med. 2012; 9:751–757. PMID: 22146048.

32. Henningsson S, Westberg L, Nilsson S, Lundström B, Ekselius L, Bodlund O, et al. Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology. 2005; 30:657–664. PMID: 15854782.

33. Hare L, Bernard P, Sánchez FJ, Baird PN, Vilain E, Kennedy T, et al. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol Psychiatry. 2009; 65:93–96. PMID: 18962445.

34. Ujike H, Otani K, Nakatsuka M, Ishii K, Sasaki A, Oishi T, et al. Association study of gender identity disorder and sex hormone-related genes. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33:1241–1244. PMID: 19604497.

35. Bentz EK, Hefler LA, Kaufmann U, Huber JC, Kolbus A, Tempfer CB. A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism. Fertil Steril. 2008; 90:56–59. PMID: 17765230.

36. Hoekzema E, Schagen SE, Kreukels BP, Veltman DJ, Cohen-Kettenis PT, Delemarre-van de, et al. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain. Psychoneuroendocrinology. 2015; 55:59–71. PMID: 25720349.

37. Zucker KJ. On the "natural history" of gender identity disorder in children. J Am Acad Child Adolesc Psychiatry. 2008; 47:1361–1363. PMID: 19034186.

38. 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. PMID: 23702447.

39. Zucker KJ, Wood H, Singh D, Bradley SJ. A developmental, biopsychosocial model for the treatment of children with gender identity disorder. J Homosex. 2012; 59:369–397. PMID: 22455326.

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

41. Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJ. The treatment of adolescent transsexuals: changing insights. J Sex Med. 2008; 5:1892–1897. PMID: 18564158.

42. 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; 40:930–936. PMID: 20094764.

43. 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; 43:1525–1533. PMID: 24619651.

44. 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. PMID: 9879847.

45. Delemarre-van de Waal HA, Cohen-Kettenis PT. Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects. Eur J Endocrinol. 2006; 155:S131–S137.

46. de Vries AL, Steensma TD, Doreleijers TA, Cohen-Kettenis PT. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med. 2011; 8:2276–2283. PMID: 20646177.

47. Cohen-Kettenis PT, Schagen SE, Steensma TD, de Vries AL, Delemarre-van de Waal HA. Puberty suppression in a gender-dysphoric adolescent: a 22-year follow-up. Arch Sex Behav. 2011; 40:843–847. PMID: 21503817.

48. 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. PMID: 25201798.

49. 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–E275. PMID: 25427144.

50. Sato T, Katagiri K, Gohbara A, Inoue K, Ogonuki N, Ogura A, et al. In vitro production of functional sperm in cultured neonatal mouse testes. Nature. 2011; 471:504–507. PMID: 21430778.

51. Yokonishi T, Sato T, Komeya M, Katagiri K, Kubota Y, Nakabayashi K, et al. Offspring production with sperm grown in vitro from cryopreserved testis tissues. Nat Commun. 2014; 5:4320. PMID: 24984101.

52. Staphorsius AS, Kreukels BP, Cohen-Kettenis PT, Veltman DJ, Burke SM, Schagen SE, et al. Puberty suppression and executive functioning: an fMRI-study in adolescents with gender dysphoria. Psychoneuroendocrinology. 2015; 56:190–199. PMID: 25837854.

53. Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, et al. Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people. J Clin Endocrinol Metab. 2003; 88:5723–5729. PMID: 14671159.

54. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011; 164:635–642. PMID: 21266549.

55. Drescher J, Byne W. Gender dysphoric/gender variant (GD/GV) children and adolescents: summarizing what we know and what we have yet to learn. J Homosex. 2012; 59:501–510. PMID: 22455333.

56. Vance SR Jr, Halpern-Felsher BL, Rosenthal SM. Health care providers' comfort with and barriers to care of transgender youth. J Adolesc Health. 2015; 56:251–253. PMID: 25620310.