Skip to main content
SpringerLink
Log in

The Role of Pubertal Hormones in the Development of Gender Identity: fMRI Studies

  • Chapter
  • First Online:
Brain Crosstalk in Puberty and Adolescence

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI,volume 13))

Abstract

The present study is the first to demonstrate that sex differences in hypothalamic activation upon smelling the chemo-signal androstadienone are not acquired during sexual maturation, under the influence of gonadal hormones during puberty, but might be considered hard-wired responses, which already can be observed in prepubertal children. Moreover, the current study is the first to explore sex-atypical hypothalamic responses to androstadienone in male and female individuals with GD at two different developmental stages. Our results suggest that individuals with GD possess certain functional brain characteristics of their experienced gender and might have undergone atypical neuronal sexual differentiation, most likely during early brain development and not during puberty. Additional analyses in other functional (e.g., mental rotation, emotional face matching, resting state data) and structural (e.g., gray and white matter volumes or diffusion tensor imaging data) MRI measures, which are in preparation, should corroborate the present preliminary findings.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. DSM-5, 5th edn. American Psychiatric Association, Arlington

    Google Scholar 

  • Bakker J, Brock O (2010) Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development. J Neuroendocrinol 22:728–732

    CAS  PubMed  Google Scholar 

  • Bao A-M, Swaab DF (2011) Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Front Neuroendocrinol 32:214–226

    Article  PubMed  Google Scholar 

  • Baroncini M, Jissendi P, Balland E, Besson P, Pruvo J-P, Francke J-P, Dewailly D, Blond S, Prevot V (2012) MRI atlas of the human hypothalamus. Neuroimage 59:168–180

    Article  PubMed  Google Scholar 

  • Baum MJ (2006) Mammalian animal models of psychosexual differentiation: when is “translation” to the human situation possible? Horm Behav 50:579–588

    Article  PubMed  Google Scholar 

  • Bentz E-K, Hefler LA, Kaufmann U, Huber JC, Kolbus A, Tempfer CB (2008) 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 90:56–59

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Brett M, Anton J, Valabregue R, Poline J-B (2002) Region of interest analysis using an SPM toolbox (abstract). In: Presented at the 8th international conference on functional mapping of the human brain. Sendai (available on CD–RO NeuroImage, Vol 16, No 2)

    Google Scholar 

  • Brock O, Baum MJ, Bakker J (2011) The development of female sexual behavior requires prepubertal estradiol. J Neurosci 31:5574–5578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burke SM, Veltman DJ, Gerber J, Hummel T, Bakker J (2012) Heterosexual men and women both show a hypothalamic response to the chemo-signal androstadienone. PLoS One 7:e40993

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carrillo B, Gómez-Gil E, Rametti G, Junque C, Gomez A, Karadi K, Segovia S, Guillamon A (2010) Cortical activation during mental rotation in male-to-female and female-to-male transsexuals under hormonal treatment. Psychoneuroendocrinology 35:1213–1222

    Article  PubMed  Google Scholar 

  • Coates S (1990) Ontogenesis of boyhood gender identity disorder. J Am Acad Psychoanal 18:414–438

    CAS  PubMed  Google Scholar 

  • Coates S, Person ES (1985) Extreme boyhood femininity: isolated behavior or pervasive disorder? J Am Acad Child Psychiatry 24:702–709

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Kettenis PT, Gooren LJ (1999) Transsexualism: a review of etiology, diagnosis and treatment. J Psychosom Res 46:315–333

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Kettenis PT, van Goozen SH (1998) Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur Child Adolesc Psychiatry 7:246–248

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Kettenis PT, van Goozen SH, Doorn CD, Gooren LJ (1998) Cognitive ability and cerebral lateralisation in transsexuals. Psychoneuroendocrinology 23:631–641

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • De Vries ALC, Cohen-Kettenis PT (2012) Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex 59:301–320

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Downey J, Ehrhardt AA, Gruen R, Bell JJ, Morishima A (1989) Psychopathology and social functioning in women with Turner syndrome. J Nerv Ment Dis 177:191–201

    Article  CAS  PubMed  Google Scholar 

  • Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E, Haro-Mora J-J, Guillamón A, Pásaro E (2013) The (CA)n polymorphism of ERβ gene is associated with FtM transsexualism. J Sex Med 11:720–728

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Gizewski ER, Krause E, Schlamann M, Happich F, Ladd ME, Forsting M, Senf W (2009) 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

    Article  PubMed  Google Scholar 

  • Gooren L (2006) The biology of human psychosexual differentiation. Horm Behav 50:589–601

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ, Spack NP, Tangpricha V, Montori VM (2009) Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 94:3132–3154

    Article  CAS  PubMed  Google Scholar 

  • Henningsson S, Westberg L, Nilsson S, Lundström B, Ekselius L, Bodlund O, Lindström E, Hellstrand M, Rosmond R, Eriksson E, Landén M (2005) Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology 30:657–664

    Article  CAS  PubMed  Google Scholar 

  • Heylens G, De Cuypere G, Zucker KJ, Schelfaut C, Elaut E, Vanden Bossche H, De Baere E, T’Sjoen G (2012) Gender identity disorder in twins: a review of the case report literature. J Sex Med 9:751–757

    Article  PubMed  Google Scholar 

  • Hines M (2010) Sex-related variation in human behavior and the brain. Trends Cogn Sci 14:448–456

    Article  PubMed Central  PubMed  Google Scholar 

  • Houk CP, Lee PA (2006) The diagnosis and care of transsexual children and adolescents: a pediatric endocrinologists’ perspective. J Pediatr Endocrinol Metab 19:103–109

    Article  PubMed  Google Scholar 

  • Hummel T, Kobal G, Gudziol H, Mackay-Sim A (2007) Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Oto-Rhino-Laryngol 264:237–243

    Article  CAS  Google Scholar 

  • Kobal G, Hummel T, Sekinger B, Barz S, Roscher S, Wolf S (1996) “Sniffin’ sticks”: screening of olfactory performance. Rhinology 34:222–226

    CAS  PubMed  Google Scholar 

  • Kobal G, Klimek L, Wolfensberger M, Gudziol H, Temmel A, Owen CM, Seeber H, Pauli E, Hummel T (2000) Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol 257:205–211

    Article  CAS  PubMed  Google Scholar 

  • Korte A, Lehmkuhl U, Goecker D, Beier KM, Krude H, Grüters-Kieslich A (2008) Gender identity disorders in childhood and adolescence: currently debated concepts and treatment strategies. Dtsch Arztebl Int 105:834–841

    PubMed Central  PubMed  Google Scholar 

  • Kreukels BPC, Cohen-Kettenis PT (2011) Puberty suppression in gender identity disorder: the Amsterdam experience. Nat Rev Endocrinol 7:466–472

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Kuyper E, Wijsen C (2014) Gender identities and gender dysphoria in the Netherlands. Arch Sex Behav 43:377–385

    Article  PubMed  Google Scholar 

  • Lemieux L, Salek-Haddadi A, Lund TE, Laufs H, Carmichael D (2007) Modelling large motion events in fMRI studies of patients with epilepsy. Magn Reson Imaging 25:894–901

    Article  PubMed  Google Scholar 

  • 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 46:904–907

    Article  PubMed Central  PubMed  Google Scholar 

  • Makris N, Swaab DF, van der Kouwe A, Abbs B, Boriel D, Handa RJ, Tobet S, Goldstein JM (2013) Volumetric parcellation methodology of the human hypothalamus in neuroimaging: normative data and sex differences. Neuroimage 69:1–10

    Article  PubMed Central  PubMed  Google Scholar 

  • Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meyenburg B (1999) Gender identity disorder in adolescence: outcomes of psychotherapy. Adolescence 34:305–313

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Nieder TO, Herff M, Cerwenka S, Preuss WF, Cohen-Kettenis PT, De Cuypere G, Haraldsen IRH, Richter-Appelt H (2011) Age of onset and sexual orientation in transsexual males and females. J Sex Med 8:783–791

    Article  PubMed  Google Scholar 

  • Rametti G, Carrillo B, Gomez-Gil E, Junque C, Segovia S, Gomez A, Guillamon A (2011a) White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J Psychiatr Res 45:199–204

    Article  PubMed  Google Scholar 

  • Rametti G, Carrillo B, Gomez-Gil E, Junque C, Zubiarre-Elorza L, Segovia S, Gomez A, Guillamon A (2011b) The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. J Psychiatr Res 45:949–954

    Article  PubMed  Google Scholar 

  • Rolstad SG, Moller A, Byrman I, Boman UW (2007) Sexual functioning and partner relationships in women with turner syndrome: some empirical data and theoretical considerations regarding sexual desire. J Sex Marital Ther 33:231–247

    Article  PubMed  Google Scholar 

  • Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB (1998) Effects of estrogen on nonverbal processing speed and motor function in girls with Turner’s syndrome. J Clin Endocrinol Metab 83:3198–3204

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Savic I, Berglund H, Gulyas B, Roland P (2001) Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Neuron 31:661–668

    Article  CAS  PubMed  Google Scholar 

  • Savic I, Garcia-Falgueras A, Swaab DF (2010) Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Prog Brain Res 186:41–62

    Article  PubMed  Google Scholar 

  • Schagen SEE, Delemarre-van de Waal HA, Blanchard R, Cohen-Kettenis PT (2012) Sibling sex ratio and birth order in early-onset gender dysphoric adolescents. Arch Sex Behav 41:541–549

    Article  PubMed Central  PubMed  Google Scholar 

  • Schöning S, Engelien A, Bauer C, Kugel H, Kersting A, Roestel C, Zwitserlood P, Pyka M, Dannlowski U, Lehmann W, Heindel W, Arolt V, Konrad C (2010) Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. J Sex Med 7:1858–1867

    Article  PubMed  Google Scholar 

  • Seckl JR, Holmes MC (2007) Mechanisms of disease: glucocorticoids, their placental metabolism and fetal “programming” of adult pathophysiology. Nat Clin Pract Endocrinol Metab 3:479–488

    Article  CAS  PubMed  Google Scholar 

  • Shaeffer AT, Lange E, Bondy CA (2008) Sexual function in women with Turner syndrome. J Women’s Health 17:27–33

    Article  Google Scholar 

  • Sisk CL, Schulz KM, Zehr J (2003) Puberty: a finishing school for male social behavior. Ann N Y Acad Sci 1007:189–198

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Steensma TD, McGuire JK, Kreukels BPC, Beekman AJ, Cohen-Kettenis PT (2013) Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry 52:582–590

    Article  PubMed  Google Scholar 

  • Swaab DF (2007) Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab 21:431–444

    Article  PubMed  Google Scholar 

  • Taziaux M, Swaab DF, Bakker J (2012) Sex differences in the neurokinin B system in the human infundibular nucleus. J Clin Endocrinol Metab 97:E2210–E2220

    Article  CAS  PubMed  Google Scholar 

  • Van Goozen SHM, Gooren LJG, Sanders G, Cohen-Kettenis PT, Slabbekoorn D (2002) Organizing and activating effects of sex hormones in homosexual transsexuals. Behav Neurosci 116:982–988

    Article  PubMed  Google Scholar 

  • Viner RM, Brain C, Carmichael P, Di Ceglie D (2005) Sex on the brain: dilemmas in the endocrine management of children and adolescents with gender identity disorder [abstract G200]. Arch Dis Child 90:A77–A81

    Google Scholar 

  • Ward OB, Ward IL, Denning JH, Hendricks SE, French JA (2002) Hormonal mechanisms underlying aberrant sexual differentiation in male rats prenatally exposed to alcohol, stress, or both. Arch Sex Behav 31:9–16

    Article  PubMed  Google Scholar 

  • World Health Organization (1992) International statistical classification of diseases and related health problems. 10th Revision (ICD-10). Chapter V. Mental and behavioural disorders, Geneva, pp F00–F9

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Zubiaurre-Elorza L, Junque C, Gómez-Gil E, Segovia S, Carrillo B, Rametti G, Guillamon A (2013) Cortical thickness in untreated transsexuals. Cereb Cortex 23:2855–2862

    Article  PubMed  Google Scholar 

  • Zubiaurre-Elorza L, Junque C, Gómez-Gil E, Guillamon A (2014) Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J Sex Med 11:1248–1261

    Article  CAS  PubMed  Google Scholar 

  • Zucker KJ, Bradley SJ (1995) Gender identity disorder and psychosexual problems in children and adolescents. Guilford Press, New York

    Google Scholar 

  • Zucker KJ, Lawrence AA (2009) Epidemiology of gender identity disorder. Int J Transgenderism 11:8–18

    Article  Google Scholar 

Download references

Acknowledgments

This study was funded by a VICI grant (453-08-003) from the Dutch Science Foundation (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) to Dr. J. Bakker. Dr. J. Bakker is a senior research associate of the Belgian Fonds National de la Recherche Scientifique.

Author information

Authors and Affiliations

  1. Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1131, 1081 HX, Amsterdam, The Netherlands

    S. M. Burke & J. Bakker

  2. Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands

    S. M. Burke & J. Bakker

  3. GIGA Neuroscience, University of Liege, Avenue de l’Hôpital 1, 4000, Liege, Belgium

    J. Bakker

Authors
  1. S. M. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Bakker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. M. Burke .

Editor information

Editors and Affiliations

  1. Developmental Neuroendocrinology Unit, G GIGA Neurosciences, University of Liège, Liège, Belgium

    Jean-Pierre Bourguignon

  2. Serv. d'endocrinologie diabetol. pédiatr, Hopital Robert Debre, Paris, Paris, France

    Jean-Claude Carel

  3. Fondation Ipsen, Boulogne-Billancourt, France

    Yves Christen

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Burke, S.M., Bakker, J. (2015). The Role of Pubertal Hormones in the Development of Gender Identity: fMRI Studies. In: Bourguignon, JP., Carel, JC., Christen, Y. (eds) Brain Crosstalk in Puberty and Adolescence. Research and Perspectives in Endocrine Interactions, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-09168-6_3

Download citation

Publish with us

Policies and ethics

Search

Navigation