Review Article | Published:

Puberty suppression in gender identity disorder: the Amsterdam experience

Nature Reviews Endocrinology volume 7, pages 466472 (2011) | Download Citation


The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment steps, and to obtain improved results in the physical appearance of those who opt to continue with sex reassignment. The effects of GnRHa are reversible. However, concerns have been raised about the risk of making the wrong treatment decisions, as gender identity could fluctuate during adolescence, adolescents in general might have poor decision-making abilities, and there are potential adverse effects on health and on psychological and psychosexual functioning. Proponents of puberty suppression emphasize the beneficial effects of GnRHa on the adolescents' mental health, quality of life and of having a physical appearance that makes it possible for the patients to live unobtrusively in their desired gender role. In this Review, we discuss the evidence pertaining to the debate on the effects of GnRHa treatment. From the studies that have been published thus far, it seems that the benefits outweigh the risks. However, more systematic research in this area is needed to determine the safety of this approach.

Key points

  • Puberty suppression as a first step in the treatment of adolescent transsexuals needs a careful clinical approach, involving mental-health practitioners to make the diagnosis and assess treatment eligibility

  • Suppression of puberty should not be started before puberty has progressed to Tanner stage 2 (when the first signs of puberty are visible)

  • Starting the process of sex reassignment with GnRHa treatment seems to result in an improved quality of life for transsexual adolescents

  • The current literature does not indicate that GnRHa treatment (followed by administration of cross-sex hormones and sex-reassignment surgery) results in physical or psychological harm

  • Additional studies are, however, needed to fully investigate the psychological and physical effects of GnRHa followed by cross-sex hormones and sex-reassignment surgery

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  1. 1.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edn, text revision (DSM-IV-TR) (American Psychiatric Association, Washington, DC, 2000).

  2. 2.

    World Health Organization International statistical classification of diseases and related health problems (ICD) 10th Revision , (2007).

  3. 3.

    , , & A sex difference in the human brain and its relation to transsexuality. Nature 378, 68–70 (1995).

  4. 4.

    et al. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J. Clin. Endocrinol. Metab. 85, 2034–2041 (2000).

  5. 5.

    & A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain 131, 3132–2146 (2008).

  6. 6.

    et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J. Psychiatr. Res. 45, 199–204 (2011).

  7. 7.

    et al. Regional gray matter variation in male-to-female transsexualism. Neuroimage 46, 904–907 (2009).

  8. 8.

    , , & Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb. Cortex 18, 1900–1908 (2008).

  9. 9.

    et al. Specific cerebral activation due to visual erotic stimuli in male-to-female transsexuals compared with male and female controls: an fMRI study. J. Sex. Med. 6, 440–448 (2009).

  10. 10.

    et al. Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. J. Sex. Med. 7, 1858–1867 (2010).

  11. 11.

    , & The heritability of gender identity disorder in a child and adolescent twin sample. Behav. Gen. 32, 251–257 (2002).

  12. 12.

    , & Masculine girls and feminine boys: genetic and environmental contributions to atypical gender development in early childhood. J. Pers. Soc. Psychol. 88, 400–412 (2005).

  13. 13.

    et al. Sex steroid related genes and male-to-female transsexualism. Psychoneuroendocrinology 30, 657–664 (2005).

  14. 14.

    et al. A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism. Fert. Steril. 90, 56–59 (2008).

  15. 15.

    et al. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol. Psychiatry 65, 93–96 (2009).

  16. 16.

    et al. A common polymorphism of the SRD5A2 gene and transsexualism. Reprod. Sci. 14, 705–709 (2007).

  17. 17.

    et al. Association study of gender identity disorder and sex hormone-related genes. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 1241–1244 (2009).

  18. 18.

    et al. WPATH standards of care for gender identity disorders—sixth version. Harry Benjamin International Gender Dysphoria Association , (2001).

  19. 19.

    et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 94, 3132–3154 (2009).

  20. 20.

    et al. The recalled childhood gender identity/gender role questionnaire: Psychometric properties. Sex Roles 54, 469–483 (2006).

  21. 21.

    Ethics and the proposed treatment for a 13-year-old with atypical gender identity. Med. J. Aust. 181, 319–321 (2004).

  22. 22.

    et al. Gender identity disorders in childhood and adolescence. Currently debated concepts and treatment strategies. Dtsch. Arztebl. Int. 105, 834–841 (2008).

  23. 23.

    & Sex reassignment of adolescent transsexuals: a follow-up study. J. Am. Acad. Child Adolesc. Psychiatry 36, 263–271 (1997).

  24. 24.

    , M & Adolescents with gender identity who were accepted or rejected for sex reassignment surgery: a prospective follow-up study. J. Am. Acad. Child Adolesc. Psychiatry 40, 472–481 (2001).

  25. 25.

    & The feasibility of endocrine interventions in juvenile transsexuals. J. Psychol. Human Sex. 8, 69–74 (1996).

  26. 26.

    & Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects. Eur. J. Endocrinol. 155 (Suppl. 1), S131–S137 (2006).

  27. 27.

    & Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur. Child Adolesc. Psychiatry 7, 246–248 (1998).

  28. 28.

    , , & Puberty suppression in adolescents with gender identity disorder: A prospective follow up study. J. Sex. Med. doi: 10.1111/j.1743-6109.2010.01943.x.

  29. 29.

    Gender Dysphoria in Adolescents; Mental Health and Treatment Evaluation. Thesis, VU University Medical Center, Amsterdam, the Netherlands (2010).

  30. 30.

    & The diagnosis and care of transsexual children and adolescents: a pediatric endocrinologists' perspective. J. Pediatr. Endocrinol. Metab. 19, 103–109 (2006).

  31. 31.

    , , & Sex on the brain: Dilemmas in the endocrine management of children and adolescents with gender identity disorder [abstract G200]. Arch. Dis. Child 90 (Suppl. 2), A77–A81 (2005).

  32. 32.

    Early physical intervention for young people with atypical gender identity development. Clin. Child Psychol. Psychiatry. 5, 220–231 (2000).

  33. 33.

    Gender atypical organization in children and adolescents: ethico-legal issues and a proposal for new guidelines. Int. J. Child. Rights 15, 365–390 (2007).

  34. 34.

    , , & Medical care for gender variant young people: dealing with the practical problems. Sexologies 17, 258–264 (2008).

  35. 35.

    & Inside Out (D'Jonge Hond B. V., The Netherlands, 2011).

  36. 36.

    & Gender Identity Disorder and Psychosexual Problems in Children and Adolescents. (Guilford Press, New York, 1995).

  37. 37.

    , , & A follow-up study of girls with gender identity disorder. Dev. Psychol. 44, 34–45 (2008).

  38. 38.

    & Psychosexual outcome of gender dysphoric children. J. Am. Acad. Child Adolesc. Psychiat. 47, 1413–1423 (2008).

  39. 39.

    The DSM diagnostic criteria for gender identity disorder in children. Arch. Sex. Behav. 39, 477–498 (2010).

  40. 40.

    , , & Desisting and persisting gender dysphoria after childhood: A qualitative follow-up study. Clin. Child Psychol. Psychiatry doi:10.1177/1359104510378303.

  41. 41.

    et al. Attitudes of adolescent cancer survivors toward end-of-life decisions for minors. Pediatrics 124, e1142–e1148 (2009).

  42. 42.

    A behavioral scientist looks at the science of adolescent brain development. Brain Cogn. 72, 160–164 (2010).

  43. 43.

    , & Ethical conflicts over the management of transsexual adolescents—Report of two cases. J. Sex. Med. 6, 3214–3220 (2009).

  44. 44.

    & Transgender youth and life-threatening behaviors. Suicide Life Threat. Behav. 37, 527–537 (2007).

  45. 45.

    & Pubertal hormones organize the adolescent brain and behavior. Front. Neuroendocrinol. 26, 163–174 (2005).

  46. 46.

    Lives in a chiaroscuro. Should we suspend the puberty of children with gender identity disorder? J. Med. Ethics 34, 580–584 (2008).

  47. 47.

    , , , & Comparing adult and adolescent transsexuals: an MMPI-2 and MMPI-A study. Psychiatry Res. 186, 414–418 (2011).

  48. 48.

    & Sex Reassignment. Thirty Years of International Follow-up Studies SRS: A Comprehensive Review, 1961–1991 (English edn.) (Symposion Publishing, Düsseldorf, Germany, 1998).

  49. 49.

    & Surgical treatment of gender dysphoria in adults and adolescents: recent developments, effectiveness, and challenges. Annu. Rev. Sex Res. 18, 178–224 (2007).

  50. 50.

    & Sex reassignment surgery: a study of 141 Dutch transsexuals. Arch. Sex. Behav. 17, 439–457 (1988).

  51. 51.

    , , & Sex reassignment: outcomes and predictors of treatment for adolescent and adult transsexuals. Psychol. Med. 35, 89–99 (2005).

  52. 52.

    et al. Psychiatric impact of gender-related abuse across the life course of male-to-female transgender persons. J. Sex Res. 47, 12–23 (2010).

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Author information


  1. Department of Medical Psychology and Medical Social Work and Neuroscience Campus, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    • Baudewijntje P. C. Kreukels
    •  & Peggy T. Cohen-Kettenis


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Both authors contributed equally to all aspects of this review.

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The authors declare no competing financial interests.

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Correspondence to Peggy T. Cohen-Kettenis.

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