Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Puberty suppression in gender identity disorder: the Amsterdam experience

Abstract

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

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  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 [online], (2007).

  3. 3

    Zhou, J. N., Hofman, M. A., Gooren, L. J. & Swaab, D. F. A sex difference in the human brain and its relation to transsexuality. Nature 378, 68–70 (1995).

    CAS  Article  Google Scholar 

  4. 4

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

    CAS  Article  Google Scholar 

  5. 5

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

    Article  Google Scholar 

  6. 6

    Rametti, G. et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J. Psychiatr. Res. 4 5, 199–204 (2011).

    Article  Google Scholar 

  7. 7

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

    Article  Google Scholar 

  8. 8

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

    CAS  Article  Google Scholar 

  9. 9

    Gizewski, E. R. 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).

    Article  Google Scholar 

  10. 10

    Schöning, S. 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).

    Article  Google Scholar 

  11. 11

    Coolidge, F. L., Thede, L. L. & Young, S. E. The heritability of gender identity disorder in a child and adolescent twin sample. Behav. Gen. 32, 251–257 (2002).

    Article  Google Scholar 

  12. 12

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

    Article  Google Scholar 

  13. 13

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

    CAS  Article  Google Scholar 

  14. 14

    Bentz, E.-K. 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).

    CAS  Article  Google Scholar 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

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

    CAS  Article  Google Scholar 

  17. 17

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

    CAS  Article  Google Scholar 

  18. 18

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

    Google Scholar 

  19. 19

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

    CAS  Article  Google Scholar 

  20. 20

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

    Article  Google Scholar 

  21. 21

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

    PubMed  Google Scholar 

  22. 22

    Korte, A. et al. Gender identity disorders in childhood and adolescence. Currently debated concepts and treatment strategies. Dtsch. Arztebl. Int. 10 5, 834–841 (2008).

    Google Scholar 

  23. 23

    Cohen-Kettenis, P. T. & van Goozen, S. H. M. Sex reassignment of adolescent transsexuals: a follow-up study. J. Am. Acad. Child Adolesc. Psychiatry 36, 263–271 (1997).

    CAS  Article  Google Scholar 

  24. 24

    Smith, Y. L. S., van Goozen, S. H. M & Cohen-Kettenis, P. T. 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).

    CAS  Article  Google Scholar 

  25. 25

    Gooren, L. J. & Delemarre-van de Waal, H. A. The feasibility of endocrine interventions in juvenile transsexuals. J. Psychol. Human Sex. 8, 69–74 (1996).

    Article  Google Scholar 

  26. 26

    Delemarre-van de Waal, H. A. & Cohen-Kettenis, P. T. 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).

    CAS  Article  Google Scholar 

  27. 27

    Cohen-Kettenis, P. T. & van Goozen, S. H. M. Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur. Child Adolesc. Psychiatry 7, 246–248 (1998).

    CAS  Article  Google Scholar 

  28. 28

    de Vries, A. L. C., Steensma, T. D., Doreleijers, T. A. H. & Cohen-Kettenis, P. T. 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

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

    Google Scholar 

  30. 30

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

    Article  Google Scholar 

  31. 31

    Viner, R. M., Brain, C., Carmichael, P. & Di Ceglie, D. 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).

    Google Scholar 

  32. 32

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

    Article  Google Scholar 

  33. 33

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

    Article  Google Scholar 

  34. 34

    Reed, B. W. D., Cohen-Kettenis, P. T., Reed, T. & Spack, N. Medical care for gender variant young people: dealing with the practical problems. Sexologies 17, 258–264 (2008).

    Article  Google Scholar 

  35. 35

    de Visser, E. & Wong, S. Inside Out (D'Jonge Hond B. V., The Netherlands, 2011).

    Google Scholar 

  36. 36

    Zucker, K. J. & Bradley, S. J. Gender Identity Disorder and Psychosexual Problems in Children and Adolescents. (Guilford Press, New York, 1995).

    Google Scholar 

  37. 37

    Drummond, K. D., Bradley, S. J., Peterson-Badali, M. & Zucker, K. J. A follow-up study of girls with gender identity disorder. Dev. Psychol. 44, 34–45 (2008).

    Article  Google Scholar 

  38. 38

    Wallien, M. S. C. & Cohen-Kettenis, P. T. Psychosexual outcome of gender dysphoric children. J. Am. Acad. Child Adolesc. Psychiat. 47, 1413–1423 (2008).

    Article  Google Scholar 

  39. 39

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

    Article  Google Scholar 

  40. 40

    Steensma, T. D., Biemond, R., De Boer, F. & Cohen-Kettenis, P. T. Desisting and persisting gender dysphoria after childhood: A qualitative follow-up study. Clin. Child Psychol. Psychiatry doi:10.1177/1359104510378303.

  41. 41

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

    Article  Google Scholar 

  42. 42

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

    Article  Google Scholar 

  43. 43

    Baltieri, D. A., Cortez, F. C. P. & de Andrade, A. G. Ethical conflicts over the management of transsexual adolescents—Report of two cases. J. Sex. Med. 6, 3214–3220 (2009).

    Article  Google Scholar 

  44. 44

    Grossman, A. H. & D'Augelli, A. R. Transgender youth and life-threatening behaviors. Suicide Life Threat. Behav. 37, 527–537 (2007).

    Article  Google Scholar 

  45. 45

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

    CAS  Article  Google Scholar 

  46. 46

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

    CAS  Article  Google Scholar 

  47. 47

    de Vries, A. L. C., Kreukels, B. P. C., Steensma, T. D., Doreleijers, T. A. H. & Cohen-Kettenis, P. T. Comparing adult and adolescent transsexuals: an MMPI-2 and MMPI-A study. Psychiatry Res. 186, 414–418 (2011).

    Article  Google Scholar 

  48. 48

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

    Google Scholar 

  49. 49

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

    Google Scholar 

  50. 50

    Kuiper, B. & Cohen-Kettenis, P. T. Sex reassignment surgery: a study of 141 Dutch transsexuals. Arch. Sex. Behav. 17, 439–457 (1988).

    CAS  Article  Google Scholar 

  51. 51

    Smith, Y. L., Van Goozen, S. H. M., Kuiper, A. J. & Cohen-Kettenis, P. T. Sex reassignment: outcomes and predictors of treatment for adolescent and adult transsexuals. Psychol. Med. 35, 89–99 (2005).

    Article  Google Scholar 

  52. 52

    Nuttbrock, L. 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).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

Both authors contributed equally to all aspects of this review.

Corresponding author

Correspondence to Peggy T. Cohen-Kettenis.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kreukels, B., Cohen-Kettenis, P. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat Rev Endocrinol 7, 466–472 (2011). https://doi.org/10.1038/nrendo.2011.78

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing