Sexual Differentiation of the Human Brain and Male/Female Behaviour

  • Dick F. SwaabEmail author


Once the differentiation of our sexual organs into male or female is settled, the next thing to be differentiated is the brain. The difference in brain structures resulting from the interaction of sex hormones and developing brain cells, is thought to be the basis of sex differences in behaviour, in gender identity, in gender roles, in our sexual orientation (hetero-, bi- or homosexuality) and in the obvious sex differences in cognition and aggressive behaviour. Our sexual orientation is determined during early foetal development, under the influence of our genetic background and of factors that affect the complex interactions between sex hormones and the developing brain. Although it has often been postulated that postnatal development is also important for the direction of our sexual differentiation, any solid proof for this is lacking. The broadly accepted view on the importance of the social environment on sexual differentiation has been extensively put into words by Simone de Beauvoir and others. It turns out, however, that sex differences revealed through play, drawings and aggression are determined by exposure to hormones in the womb rather than by what society demands later on. The apparent impossibility to get someone to change their sexual orientation is a major argument against the importance of the social environment in the emergence of homosexuality, as well as against the idea that homosexuality is a lifestyle choice. Our sexual orientation is fixed during prenatal development and is beyond influencing in adulthood. Apparently, and despite the feminist ideals, we tend to choose what best fits our programmed (by natural sexual selection developed) brains. Our sexually differential brains will not lend themselves for a completely equal division of tasks between men and women in the family or on the labour market. There is great public interest in research of the brain and in research of our sexual behaviour, but the combination of these two subjects has turned out to be dynamite.


Sexual Orientation Gender Identity Congenital Adrenal Hyperplasia Sexual Differentiation Heterosexual Woman 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



I want to thank Mrs. Wilma Verweij for her professional help with the English.


  1. Alexander, G.M., & Hines, M. (2002). Sex differences in response to children’s toys in nonhuman primates (Cercopithecus aethiops sabaeus). Evolution and Human Behavior, 23, 467–479.CrossRefGoogle Scholar
  2. Allen, L.S., & Gorski, R.A. (1992). Sexual orientation and the size of the anterior commissure in the human brain. Proceedings of the National Academy of Sciences of the United States of America, 89, 7199–7202.CrossRefGoogle Scholar
  3. Bailey, J.M., & Bell, A.P. (1993). Familiality of female and male homosexuality. Behavior Genetics, 23, 313–322.CrossRefGoogle Scholar
  4. Bailey, J.M., Willerman, L., & Parks, C. (1991). A test of the maternal stress theory of human male homosexuality. Archives of Sexual Behavior, 20, 277–293.CrossRefGoogle Scholar
  5. Bakker, J., De Mees, C., Douhard, Q., Balthazart, J., Gabant, P., Szpirer, J., & Szpirer, C. (2006). Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nature Neuroscience, 9, 220–226.CrossRefGoogle Scholar
  6. Berglund, H., Lindström, P., & Savic, I. (2006). Brain response to putative pheromones in lesbian women. Proceedings of the National Academy of Sciences of the United States of America, 103, 8269–8274.CrossRefGoogle Scholar
  7. Blanchard, R. (2001). Fraternal birth order and the maternal immune hypothesis of male homosexuality. Hormones and Behavior, 40, 105–114.CrossRefGoogle Scholar
  8. Bogaert, A.F. (2003). The interaction of fraternal birth order and body size in male sexual orientation. Behavioral Neuroscience, 117, 381–384.CrossRefGoogle Scholar
  9. Burns, J.M., & Swerdlow, R.H. (2003). Right orbitofrontal tumor with pedophilia symptom and constructional apraxia sign. Archives of Neurology, 60, 437–440.CrossRefGoogle Scholar
  10. Camperio-Ciani, A., Corna, F., & Capiluppi, C. (2004). Evidence for maternally inherited factors favouring male homosexuality and promoting female fecundity. Proceedings of the Royal Society B: Biological Sciences, 271, 2217–2221.CrossRefGoogle Scholar
  11. Chung, W.C., De Vries, G.J., & Swaab, D.F. (2002). Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. The Journal of Neuroscience, 22, 1027–1033.Google Scholar
  12. Cohen-Kettenis, P.T. (2005). Gender change in 46, XY persons with 5α-Reductase-2 deficiency and 17β-hydroxysteroid dehydrogenase-3 deficiency. Archives of Sexual Behavior, 34, 399–410.CrossRefGoogle Scholar
  13. Cohen-Kettenis, P.T., & Gooren, L.J.G. (1999). Transsexualism: a review of etiology, diagnosis and treatment. Journal of Psychosomatic Research, 46, 315–333.CrossRefGoogle Scholar
  14. Colapinto, J. (2001). As Nature Made Him. The Boy Who Was Raised As a Girl. New York, NY: Harper Collins Publishers Inc.Google Scholar
  15. Coolidge, F.L., Thede, L.L., & Young, S.E. (2002). The heritability of gender identity disorder in a child and adolescent twin sample. Behavior Genetics, 32, 251–257.CrossRefGoogle Scholar
  16. Dessens, A.B., Cohen-Kettenis, P.T., Mellenbergh, G.J., Van de Poll, N.E., Koppe, J.G., & Boer, K. (1999). Prenatal exposure to anticonvulsants and psychosexual development. Archives of Sexual Behavior, 28, 31–44.CrossRefGoogle Scholar
  17. Dessens, A.B., Slijper, F.M., & Drop, S.L. (2005). Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Archives of Sexual Behavior, 34, 389–397.CrossRefGoogle Scholar
  18. Dewing, P., Shi, T., Horvath, S., & Vilain, E. (2003). Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Molecular Brain Research, 118, 82–90.CrossRefGoogle Scholar
  19. De Zegher, F., Devlieger, H., & Veldhuis, J.D. (1992). Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth. Pediatric Research, 32, 605–607.Google Scholar
  20. Diamond, M., & Sigmundson, H.K. (1997). Sex reassignment at birth. Long-term review and clinical implications. Archives of Pediatrics & Adolescent Medicine, 151, 298–304.Google Scholar
  21. Dieckmann, G., & Hassler, R. (1977). Treatment of sexual violence by stereotactic hypothalamotomy. In W.H. Sweet, S. Obrador, & J.G. Martin-Rodriguez (Eds.), Neurosurgical Treatment in Psychiatry, Pain, and Epilepsy (451–462). Baltimore, MD: University Park Press.Google Scholar
  22. Ehrhardt, A.A., Meyer-Bahlburg, H.F.L., Rosen, L.R., Feldman, J.F., Veridiano, N.P., Zimmerman, I., & McEwen, B.S. (1985). Sexual orientation after prenatal exposure to exogenous estrogen. Archives of Sexual Behavior, 14, 57–75.CrossRefGoogle Scholar
  23. Ellis, L., Ames, M.A., Peckham, W., & Burke, D. (1988). Sexual orientation of human offspring may be altered by severe maternal stress during pregnancy. Journal of Sexual Research, 25, 152–157.CrossRefGoogle Scholar
  24. Ellis, L., & Cole-Harding, S. (2001). The effects of prenatal stress, and of prenatal alcohol and nicotine exposure, on human sexual orientation. Physiology & Behavior, 74, 213–226.CrossRefGoogle Scholar
  25. Ellis, L., & Hellberg, J. (2005). Fetal exposure to prescription drugs and adult sexual orientation. Personality and Individual Differences, 38, 225–236.CrossRefGoogle Scholar
  26. Finegan, J.-A., Bartleman, B., & Wong, P.Y. (1989). A window for the study of prenatal sex hormone influences on postnatal development. The Journal of General Psychology, 150, 101–112.CrossRefGoogle Scholar
  27. Garcia-Falgueras, A., & Swaab, D.F. (2008). A sex difference in the hypothamaic uncinate nucleus: relationship to gender identity. Brain, 131, 3132–3146.CrossRefGoogle Scholar
  28. Green, R. (1978). Sexual identity of 37 children raised by homosexual or transsexual parents. The American Journal of Psychiatry, 135, 692–697.Google Scholar
  29. Hare, L., Bernard, P., Sánchez, F.J., et al. (2009). Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biological Psychiatry, 65, 93–96.CrossRefGoogle Scholar
  30. Henningsson, S., Westberg, L., Nilsson, S., Lundstrom, B., Ekselius, L., Bodlund, O., Lindstrom, E., Hellstrand, M., Rosmond, R., Eriksson, E., & Landen, M. (2005). Sex steroid-related genes and male-to-female transsexualism. Psychoneuro endocrinology, 30, 657–664.CrossRefGoogle Scholar
  31. Hughes, I.A., Houk, C., Ahmed, S.F., Lee, P.A., & LWPES/ESPE Consensus Group. (2006). Consensus statement on management of intersex disorders. Archives of Diseases in Childhood, 91, 554–563.CrossRefGoogle Scholar
  32. Iijima, M., Arisaka, O., Minamoto, F., & Arai, Y. (2001). Sex differences in children’s free drawings: a study on girls with congenital adrenal hyperplasia. Hormones and Behavior, 40, 90–104.CrossRefGoogle Scholar
  33. Imperato-McGinley, J., Peterson, R.E., Gautier, T., & Sturla, E. (1979). Male pseudohermaphroditism secondary to 5αReductase deficiency – a model for the role of androgens in both the development of the male phenotype and the evolution of a male gender identity. Journal of Steroid Biochemistry, 11(1B), 637–645.CrossRefGoogle Scholar
  34. Kellermann, A.L., & Mercy, J.A. (1992). Men, women, and murder: gender-specific differences in rates of fatal violence and victimization. The Journal of Trauma, 33, 1–5.CrossRefGoogle Scholar
  35. Kinnunen, L.H., Moltz, H., Metz, J., & Cooper, M. (2004). Differential brain activation in exclusively homosexual and heterosexual men produced by the selective serotonin reuptake inhibitor, fluoxetine. Brain Research, 1024, 251–254.CrossRefGoogle Scholar
  36. Kranz, F., & Ishai, A. (2006). Face perception is modulated by sexual preference. Current Biology, 16, 63–68.CrossRefGoogle Scholar
  37. Kruijver, F.P.M., Zhou, J.N., Pool, C.W., Hofman, M.A., Gooren, L.J.G., & Swaab, D.F. (2000). Male-to-female transsexuals have female neuron numbers in a limbic nucleus. The Journal of Clinical Endocrinology and Metabolism, 85, 2034–2041.CrossRefGoogle Scholar
  38. LeVay, S. (1991). A difference in hypothalamic structure between heterosexual and homosexual men. Science, 253, 1034–1037.CrossRefGoogle Scholar
  39. LeVay, S. (1996). Queer Science. The Use and Abuse of Research into Homosexuality. Cambridge, MA: The MIT Press.Google Scholar
  40. LeVay, S., & Hamer, D.H. (1994). Evidence for a biological influence in male homosexuality. Scientific American, 270, 44–49.CrossRefGoogle Scholar
  41. Mayer, A., Swaab, D.F., Pilgrim, C., Reisert, I., & Lahr, G. (1998). Genes involved in male sex determination are expressed in adult human brain. Neurogenetics, 1, 281–288.CrossRefGoogle Scholar
  42. Meyer-Bahlburg, H.F.L., Ehrhardt, A.A., Rosen, L.R., Gruen, R.S., Veridiano, N.P., Van, F.H., & Neuwalder, H.F. (1995). Prenatal estrogens and the development of homosexual orientation. Developmental Psychology, 31, 12–21.CrossRefGoogle Scholar
  43. Meyer-Bahlburg, H.F.L., Gruen, R.S., New, M.I., Bell, J.J., Morishima, A., Shimshi, M., Bueno, Y., Vargas, I., & Baker, S.W. (1996). Gender change from female to male in classical congenital adrenal hyperplasia. Hormones and Behavior, 30, 319–332.CrossRefGoogle Scholar
  44. Miller, B.L., Cummings, J.L., McIntyre, H., Ebers, G., & Grode, M. (1986). Hypersexuality or altered sexual preference following brain injury. Journal of Neurology, Neurosurgery, and Psychiatry, 49, 867–873.CrossRefGoogle Scholar
  45. Money, J. (1975). Ablatio penis: normal male infant sex-reassigned as a girl. Archives of Sexual Behavior, 4, 65–71.CrossRefGoogle Scholar
  46. Money, J., & Erhardt, A.A. (1972). Man and Woman, Boy and Girl: The Differentiation and Dimorphism of Gender Identity from Conception to Maturity. Baltimore, MD: Johns Hopkins University Press.Google Scholar
  47. Nordenström, A., Servin, A., Bohlin, G., Larsson, A., & Wedell, A. (2002). Sex-typed toy play behavior correlates with the degree of prenatal androgen exposure assessed by CYP21 genotype in girls with congenital adrenal hyperplasia. The Journal of Clinical Endocrinology and Metabolism, 87, 5119–5124.CrossRefGoogle Scholar
  48. Quigley, C.A. (2002). The postnatal gonadotropin and sex steroid surge – insights from the androgen insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism, 87, 24–28.CrossRefGoogle Scholar
  49. Savic, I., Berglund, H., & Lindstrom, P. (2005). Brain response to putative pheromones in homosexual men. Proceedings of the National Academy of Sciences of the United States of America, 102, 7356–7361.CrossRefGoogle Scholar
  50. Swaab, L.I. (1964). Enige resultaten bij de toepassing van orale ovulatieremmers (orale anticonceptie). Nederlands Tijdschrift voor Geneeskunde, 108(22), 1070–1076.Google Scholar
  51. Swaab, D.F. (2004). The human hypothalamus. Basic and Clinical Aspects. Part II: Neuropathology of the Hypothalamus and Adjacent Brain Structures. Handbook of Clinical Neurology. M.J. Aminoff, F. Boller, & D.F. Swaab. (Series Editors). Amsterdam: Elsevier, 596 pp.Google Scholar
  52. Swaab, D.F., & Fliers, E. (1985). A sexually dimorphic nucleus in the human brain. Science, 228, 1112–1115.CrossRefGoogle Scholar
  53. Swaab, D.F., & Hofman, M.A. (1990). An enlarged suprachiasmatic nucleus in homosexual men. Brain Research, 537, 141–148.CrossRefGoogle Scholar
  54. Swaab, D.F., Slob, A.K., Houtsmuller, E.J., Brand, T., & Zhou, J.N. (1995). Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of ‘bisexual’ adult male rats following perinatal treatment with the aromatase blocker ATD. Developmental Brain Research, 85, 273–279.CrossRefGoogle Scholar
  55. Titus-Ernstoff, L., Perez, K., Hatch, E.E., Troisi, R., Palmer, J.R., Hartge, P., Hyer, M., Kaufman, R., Adam, E., Strohsnitter, W., Noller, K., Pickett, K.E., & Hoover, R. (2003). Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology, 14, 155–160.CrossRefGoogle Scholar
  56. Williams, M.A., & Mattingley, J.B. (2006). Do angry men get noticed? Current Biology, 16, R402–R404.CrossRefGoogle Scholar
  57. Wilson, J.D., Griffin, J.E., & Russell, D.W. (1993). Steroid 5a-reductase 2 deficiency. Endocrine Reviews, 14, 577–593.Google Scholar
  58. Wisniewski, A.B., Migeon, C.J., Meyer-Bahlburg, H.F.L., Gearhart, J.P., Berkovitz, G.D., Brown, T.R., & Money, J. (2000). Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. The Journal of Clinical Endocrinology and Metabolism, 85, 2664–2669.CrossRefGoogle Scholar
  59. Zhou, J.N., Hofman, M.A., Gooren, L.J.G., & Swaab, D.F. (1995). A sex difference in the human brain and its relation to transsexuality. Nature, 378, 68–70.CrossRefGoogle Scholar
  60. Zucker, K.J., Bradley, S.J., Oliver, G., Blake, J., Fleming, S., & Hood, J. (1996). Psychosexual development of woman with congenital adrenal hyperplasia. Hormones and Behavior, 30, 300–318.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.University of AmsterdamAmsterdamThe Netherlands
  2. 2.Netherlands Institute for NeuroscienceAmsterdamThe Netherlands

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