KEY POINTS * Puberty suppression using gonadotropin-releasing hormone analogues is prescribed to relieve the distress associated with pubertal development in adolescents with gender

dysphoria, in order to provide time for further exploration * Treating prepubertal individuals with gender dysphoria is particularly controversial owing to their unstable pattern of gender

variance compared with gender-dysphoric adolescents and adults * The absence of robust data in support of or against the use of puberty suppression in childhood-onset gender dysphoria has

led to inconsistencies between health-care pathways across different centres * The paucity of evidence of the effect of puberty suppression on health-related outcome measures calls for

increasingly accepted as an intervention during the early stages of puberty (Tanner stage 2–3) in individuals with clear signs of childhood-onset gender dysphoria. However, lowering the age

threshold for using medical intervention for children with gender dysphoria is still a matter of contention, and is more controversial than treating the condition in adolescents and adults,

as children with gender dysphoria are more likely to express an unstable pattern of gender variance. Furthermore, concerns have been expressed regarding the risks of puberty suppression,

which are poorly understood, and the child's ability to make decisions and provide informed consent. However, even if the limited data available mean that it is not possible to make a

conclusive treatment recommendation, some safety criteria for puberty suppression can be identified and applied. Access through your institution Buy or subscribe This is a preview of

subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only

$17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout

ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS GONADOTROPIN-RELEASING

HORMONE ANALOGS TREATMENT IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AND EARLY FAST PUBERTY Article 07 November 2023 EFFECT OF GONADOTROPIN-RELEASING HORMONE AGONIST MONOTHERAPY AND

COMBINATION THERAPY WITH GROWTH HORMONE ON FINAL ADULT HEIGHT IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY Article Open access 23 January 2023 TESTOSTERONE THERAPY IN CHILDREN AND ADOLESCENTS:

TO WHOM, HOW, WHEN? Article 07 January 2022 REFERENCES * Sohn, M. & Bosinski, H. A. Gender identity disorders: diagnostic and surgical aspects. _J. Sex. Med._ 4, 1193–1207 (2007). PubMed

  Google Scholar  * Benjamin, H. _The Transsexual Phenomenon_ (Julian Press, 1966). Google Scholar  * Coleman, E. _ et al_. Standards of care (SOC) for the health of transsexual,

transgender, and gender nonconforming people, 7th version. _Int. J. Transgenderism_ 13, 165–232 (2012). Google Scholar  * Hidalgo, M. A. _ et al_. The gender affirmative model: what we know

and what we aim to learn. _Hum. Dev._ 56, 285–290 (2013). Google Scholar  * American Psychiatric Association. _Quick Reference to the Diagnostic Criteria From DSM-III_ (American Psychiatric

Association, 1980). * American Psychiatric Association. _Diagnostic Criteria From DSM-IV_ (American Psychiatric Association, 1994). * American Psychiatric Association. _Diagnostic Criteria

From DSM-IV-TR_ (American Psychiatric Association, 2000). * American Psychiatric Association. _Desk Reference to the Diagnostic Criteria From DSM-5_ (American Psychiatric Association, 2013).

* Drescher, J. Queer diagnoses: parallels and contrasts in the history of homosexuality, gender variance, and the diagnostic and statistical manual. _Arch. Sex. Behav._ 39, 427–460 (2010).

PubMed  Google Scholar  * Money, J. & Tucker, P. _Sexual Signatures: On Being a Man or a Woman_ (Little Brown & Co., 1975). Google Scholar  * Fagot, B. L. & Leinbach, M. D.

Gender identity: some thoughts on an old concept. _J. Am. Acad. Child Psychiatry_ 24, 684–688 (1985). CAS  PubMed  Google Scholar  * Stoller, R. J. A contributiuon to the study of gender

identity. _Int. J. Psychoanal._ 45, 220–226 (1964). CAS  PubMed  Google Scholar  * Maccoby, E. E. _The Two Sexes: Growing Up Apart, Coming Together_ (Harvard Univ. Press, 1998). Google

Scholar  * Szkrybalo, J. & Ruble, D. N. “God made me a girl”: sex-category constancy judgments and explanations revisited. _Dev. Psychol._ 35, 392–402 (1999). CAS  PubMed  Google Scholar

  * Ruble, D. N., Martin, C. L. & Berenbaum, S. A. _Handbook of Child Psychology Wiley Online Library_ http://onlinelibrary.wiley.com/doi/10.1002/9780470147658.chpsy0314/abstract (2007).

Google Scholar  * Zucker, K. J. _ et al_. Gender constancy judgments in children with gender identity disorder: evidence for a developmental lag. _Arch. Sex. Behav._ 28, 475–502 (1999). CAS

  PubMed  Google Scholar  * Durkin, K. _Developmental Social Psychology: From Infancy to Old Age_ (Blackwell, 1995). Google Scholar  * Martin, C. L., Ruble, D. N. & Szkrybalo, J.

Cognitive theories of early gender development. _Psychol. Bull._ 128, 903–933 (2002). PubMed  Google Scholar  * Goldner, V. Trans: gender in free fall. _Psychoanal. Dialogues_ 21, 159–171

(2011). Google Scholar  * Egan, S. K. & Perry, D. G. Gender identity: a multidimensional analysis with implications for psychosocial adjustment. _Dev. Psychol._ 37, 451–463 (2001). CAS 

PubMed  Google Scholar  * Zucker, K. J., Lawrence, A. A. & Kreukels, B. P. Gender dysphoria in adults. _Annu. Rev. Clin. Psychol._ 28, 217–247 (2016). Google Scholar  * Zucker, K. J.

& Lawrence, A. A. Epidemiology of gender identity disorder. _Int. J. Transgenderism_ 11, 8–18 (2009). Google Scholar  * Bonifacio, H. J. & Rosenthal, S. M. Gender variance and

dysphoria in children and adolescents. _Pediatr. Clin. North Am._ 62, 1001–1016 (2015). PubMed  Google Scholar  * Cohen-Kettenis, P. T. & Klink, D. Adolescents with gender dysphoria.

_Best Pract. Res. Clin. Endocrinol. Metab._ 29, 485–495 (2015). PubMed  Google Scholar  * Arcelus, J. _ et al_. Systematic review and meta-analysis of prevalence studies in transsexualism.

_Eur. Psychiatry_ 30, 807–815 (2015). CAS  PubMed  Google Scholar  * Aitken, M. _ et al_. Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. _J. Sex.

Med._ 12, 756–763 (2015). PubMed  Google Scholar  * Achenbach, T. M., Howell, C. T., Quay, H. C. & Conners, C. K. National survey of problems and competencies among four- to

sixteen-year-olds: parents' reports for normative and clinical samples. _Monogr. Soc. Res. Child Dev._ 56, 1–131 (1991). CAS  PubMed  Google Scholar  * Sandberg, D. E., Meyerbahlburg,

H. F. L., Ehrhardt, A. A. & Yager, T. J. The prevalence of gender atypical behavior in elementary-school-children. _J. Am. Acad. Child Adolesc. Psychiatry_ 32, 306–314 (1993). CAS 

PubMed  Google Scholar  * Kuyper, L. & Wijsen, C. Gender identities and gender dysphoria in the Netherlands. _Arch. Sex. Behav._ 43, 377–385 (2014). PubMed  Google Scholar  * Wallien, M.

S. C. & Cohen-Kettenis, P. T. Psychosexual outcome of gender-dysphoric children. _J. Am. Acad. Child Adolesc. Psychiatry_ 47, 1413–1423 (2008). PubMed  Google Scholar  * Zucker, K.

& Bradley, S. _Gender Identity Disorder and Psychosexual Problems in Children and Adolescents_ (Guilford Press, 1995). Google Scholar  * Steensma, T. _From Gender Variance to Gender

Dysphoria. Psychosexual Development of Gender Atypical Children and Adolescents_ (Ridderprint, 2013). Google Scholar  * Menvielle, E., Perrin, E. & Tuerk, C. The beat of a different

drummer: children who do not follow gender-typical expectations: children who do not follow gender-typical expectations. _Contemp. Pediatr._ 22, 38–46 (2005). Google Scholar  * Gray, S. C.,

Carter, A. S. & Levitt, H. A critical review of assumptions about gender variant children in psychological research. _J. Gay Lesbian Mental Health_ 16, 4–30 (2012). Google Scholar  *

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_ 16, 499–516 (2011). PubMed  Google Scholar  * Steensma, T. D., McGuire, J. K., Kreukels, B. P. C., Beekman, A. J. & Cohen-Kettenis, P. T. Factors associated with desistence

and persistence of childhood gender dysphoria: a quantitative follow-up study. _J. Am. Acad. Child Adolesc. Psychiatry_ 52, 582–590 (2013). PubMed  Google Scholar  * 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). PubMed  Google Scholar  * Lawrence, A. A.

Sexual orientation versus age of onset as bases for typologies (subtypes) for gender identity disorder in adolescents and adults. _Arch. Sex. Behav._ 39, 514–545 (2010). PubMed  Google

Scholar  * Byne, W. _ et al_. Report of the American Psychiatric Association Task Force on Treatment of Gender Identity Disorder. _Arch. Sex. Behav._ 41, 759–796 (2012). PubMed  Google

Scholar  * Costa, R. _ et al_. Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. _J. Sex. Med._ 12, 2206–2214 (2015). CAS  PubMed

  Google Scholar  * de Vries, A. L. C. _ et al_. Young adult psychological outcome after puberty suppression and gender reassignment. _Pediatrics_ 134, 696–704 (2014). PubMed  Google Scholar

  * 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._ 8, 2276–2283 (2011). PubMed  Google Scholar  * Zucker, K. J. Children with gender identity disorder: is there a best practice? _Neuropsychiat. Enfan._ 56, 358–364 (2008).

Google Scholar  * Green, R. _The 'Sissy Boy Syndrome' and the Development of Homosexuality_ (Yale Univ. Press, 1987). Google Scholar  * Rekers, G. A. _Growing Up Straight: What

Families Should Know About Homosexuality_ (Moody Press, 1982). Google Scholar  * Cohen-Kettenis, P. T., Steensma, T. D. & de Vries, A. L. C. Treatment of adolescents with gender

dysphoria in the Netherlands. _Child Adolesc. Psychiatr. Clin. N. Am._ 20, 689–700 (2011). PubMed  Google Scholar  * Cohen-Kettenis, P. T., Schagen, S. E., Steensma, T. D., de Vries, A. L.

& Delemarre-van de Waal, H. A. Puberty suppression in a gender-dysphoric adolescent: a 22-year follow-up. _Arch. Sex. Behav._ 40, 843–847 (2011). PubMed  PubMed Central  Google Scholar 

* Staphorsius, A. S. _ et al_. Puberty suppression and executive functioning: an fMRI-study in adolescents with gender dysphoria. _Psychoneuroendocrinology_ 56, 190–199 (2015). PubMed 

Google Scholar  * 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. _Clin. Endocrinol. Metab._ 100, E270–E275 (2015). CAS  Google Scholar  * Ehrensaft, D. Boys will be girls, girls will be

boys: children affect parents as parents affect children in gender nonconformity. _Psychoanal. Psychol._ 28, 528–548 (2011). Google Scholar  * Hill, D. B., Menvielle, E., Sica, K. M. &

Johnson, A. An affirmative intervention for families with gender variant children: parental ratings of child mental health and gender. _J. Sex. Marital Ther._ 36, 6–23 (2010). PubMed  Google

Scholar  * Pleak, R. R. _Ethical Issues in Diagnosing and Treating of Gender-Dysphoric Children and Adolescents_ (ed. Rottnek, M.) (New York Univ. Press, 1999). Google Scholar  *

Meyer-Bahlburg, H. F. L. Gender assignment and reassignment in intersexuality: controversies, data, and guidelines for research. _Adv. Exp. Med. Biol._ 511, 199–223 (2002). PubMed  Google

Scholar  * Edwards-Leeper, L. & Spack, N. P. Psychological evaluation and medical treatment of transgender youth in an interdisciplinary 'gender management service' (GeMS) in a

major pediatric center. _J. Homosex._ 59, 321–336 (2012). PubMed  Google Scholar  * Cohen-Kettenis, P. T. & Gooren, L. J. G. Transsexualism: a review of etiology, diagnosis and

treatment. _J. Psychosom. Res._ 46, 315–333 (1999). CAS  PubMed  Google Scholar  * 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  PubMed  Google Scholar  * Colizzi, M., Costa, R., Pace, V. & Todarello, O. Hormonal treatment reduces psychobiological distress in

gender identity disorder, independently of the attachment style. _J. Sex. Med._ 10, 3049–3058 (2013). PubMed  Google Scholar  * Colizzi, M., Costa, R. & Todarello, O. Transsexual

patients' psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: results from a longitudinal study. _Psychoneuroendocrinology_ 39, 65–73 (2014).

CAS  PubMed  Google Scholar  * Colizzi, M., Costa, R. & Todarello, O. Dissociative symptoms in individuals with gender dysphoria: is the elevated prevalence real? _Psychiatry Res._ 226,

173–180 (2015). PubMed  Google Scholar  * 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, S131–S137 (2006). CAS  Google Scholar  * Smith, Y. L. S., van Goozen, S. H. M. & Cohen-Kettenis, P. T. Adolescents with

gender identity disorder 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  PubMed 

Google Scholar  * Smith, Y. L. S., 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). PubMed  Google Scholar  * Colizzi, M. _ et al_. Concomitant psychiatric problems and hormonal treatment induced metabolic syndrome in gender

dysphoria individuals: a 2 year follow-up study. _J. Psychosom. Res._ 78, 399–406 (2015). PubMed  Google Scholar  * 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  PubMed  Google Scholar  * Kreukels, B. P. C. & Cohen-Kettenis, P. T. Puberty

suppression in gender identity disorder: the Amsterdam experience. _Nat. Rev. Endocrinol._ 7, 466–472 (2011). CAS  PubMed  Google Scholar  * Bockting, W. in _The International Encyclopedia

of Human Sexuality_ (ed Bolin, A.) 583–625 (2015). Google Scholar  * Lothstein, L. M. & Levine, S. B. Expressive psychotherapy with gender dysphoric patients. _Arch. Gen. Psychiatry_ 38,

924–929 (1981). CAS  PubMed  Google Scholar  * Carel, J. C. & Léger, J. Clinical practice. Precocious puberty. _N. Engl. J. Med._ 358, 2366–2377 (2008). CAS  Google Scholar  Download

references ACKNOWLEDGEMENTS Authors would like to thank all patients and colleagues met during their years of clinical research activity. A special thank goes to the Gender Unit at the

University of Bari, Italy, and the Gender Identity Development Service at the Tavistock and Portman NHS Foundation Trust, United Kingdom. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Gender

Identity Development Service, Tavistock and Portman NHS Foundation Trust, Tavistock Centre, 120 Belsize Lane, London, NW3 5BA, UK Rosalia Costa & Polly Carmichael * Department of

Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK Marco Colizzi Authors * Rosalia Costa View

author publications You can also search for this author inPubMed Google Scholar * Polly Carmichael View author publications You can also search for this author inPubMed Google Scholar *

Marco Colizzi View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS R.C. and M.C. researched data for the article, and wrote the manuscript. All

authors made substantial contributions to discussions of content and reviewed and edited the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Rosalia Costa. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE Costa, R., Carmichael, P. & Colizzi, M. To treat or not to treat: puberty suppression in childhood-onset gender dysphoria. _Nat Rev Urol_ 13, 456–462

(2016). https://doi.org/10.1038/nrurol.2016.128 Download citation * Published: 19 July 2016 * Issue Date: August 2016 * DOI: https://doi.org/10.1038/nrurol.2016.128 SHARE THIS ARTICLE Anyone

you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by

the Springer Nature SharedIt content-sharing initiative