Early androgen exposure and human gender development

Biology of Sex Differences

Volumn 6, Issue 1, 2015, Pages

  Hines, Melissa ^a   Constantinescu, Mihaela ^a   Spencer, Debra ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Amniotic; Androgen; Autism; Behavior; Gender; Human; Mini puberty; Play; Sex; Testosterone

Indexed keywords

EID: 84924974561     PISSN: None     EISSN: 20426410     Source Type: Journal    
DOI: 10.1186/s13293-015-0022-1     Document Type: Review

References (82)

1. Arnold AP. The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm Behav. 2009;55:570-8.
2. Hines M. Brain gender. New York: Oxford University Press; 2004.
3. Arnold AP, Gorski RA. Gonadal steroid induction of structural sex differences in the central nervous system. Annu Rev Neurosci. 1984;7:413-42.
4. McCarthy MM, De Vries GJ, Forger NG. Sexual differentiation of the brain: mode, mechanisms, and meaning. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT, editors. Hormones, brain and behavior, vol. 3. 2nd ed. San Diego: Academic; 2009. p. 1707-44.
5. Maccoby EE, Jacklin CN. The psychology of sex differences. Stanford, CA: Stanford University Press; 1974.
6. Simmons JP, Nelson LD, Simonsohn U. False-positive psychology: undisclosed flexibility in data collection and analysis allows presenting anything as significant. Psychol Sci. 2011;22:1359-66.
7. Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2:e124.
8. Hyde JS. The gender similarities hypothesis. Am Psychol. 2005;60:581-92.
9. Hines M. Gendered development. In: Lerner RM, Lamb ME, editors. Handbook of Child Development and Developmental Science. 7th ed. Hoboken, NJ: Wiley; 2015.
10. Hines M. Sex-related variation in human behavior and the brain. Trends Cogn Sci. 2010;14:448-56.
11. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, N.J.: Lawrence Erlbaum Associates; 1988.
12. Rutter M, Caspi A, Moffitt TE. Using sex differences in psychopathology to study causal mechanisms: unifying issues and research strategies. J Child Psychol Psychiatry. 2003;44:1092-115.
13. Forest MG, Cathiard AM, Bertrand JA. Evidence of testicular activity in early infancy. J Clin Endocrinol Metabol. 1973;41:751-60.
14. Winter JSD, Hughes IA, Reyes FI, Faiman C. Pituitary-gonadal relations in infancy. 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metabol. 1976;42:679-86.
15. Kuiri-Hanninen T, Seuri R, Tyrvainen E, Turpeinen U, Hamalainen E, Stenman UH, et al. Increased activity of the hypothalamic-pituitary-testicular axis in infancy results in increased androgen action in premature boys. J Clin Endocrinol Metabol. 2011;96:98-105.
16. Constantinescu M, Hines M. Relating prenatal testosterone exposure to postnatal behavior in typically developing children: methods and findings. Child Dev Perspect. 2012;6:407-13.
17. Berenbaum SA, Bryk KK, Nowak N, Quigley CA, Moffat S. Fingers as a marker of prenatal androgen exposure. Endocrinology. 2009;150:5119-24.
18. Hines M. Gender development and the human brain. Annu Rev Neurosci. 2011;34:67-86.
19. Ehrhardt AA, Money J. Progestin-induced hermaphroditism: IQ and psychosexual identity in a study of ten girls. J Sex Res. 1967;3:83-100.
20. Ehrhardt AA, Meyer-Bahlburg HFL, Feldman JF, Ince SE. Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens. Arch Sex Behav. 1984;13:457-77.
21. Ehrhardt AA, Grisanti GC, Meyer-Bahlburg HFL. Prenatal exposure to medroxyprogesterone acetate (MPA) in girls. Psychoneuroendocrinology. 1977;2:391-8.
22. Meyer-Bahlburg HFL, Grisanti GC, Ehrhardt AA. Prenatal effects of sex hormones on human male behavior: medroxyprogesterone acetate (MPA). Psychoneuroendocrinology. 1977;2:383-90.
23. Hines M, Ahmed SF, Hughes I. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch Sex Behav. 2003;32:93-101.
24. Jurgensen M, Hiort O, Holterhus P-M, Thyen U. Gender role behavior in children with XY karyotype and disorders of sex development. Horm Behav. 2007;51:443-53.
25. Dittmann RW, Kappes ME, Kappes MH. Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia. Psychoneuroendocrinology. 1992;17:153-70.
26. Frisén J, Nordenstrom A, Falhammar H, Filipsson H, Holmdahl G, Janson PO, et al. Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency. J Clin Endocrinol Metabol. 2009;94:3432-9.
27. Meyer-Bahlburg HFL, Dolezal C, Baker SW, New MI. Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav. 2008;37:85-99.
28. Hines M, Brook C, Conway GS. Androgen and psychosexual development: core gender identity, sexual orientation and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH). J Sex Res. 2004;41:75-81.
29. Wisniewski AB, Migeon CJ, Meyer-Bahlburg HFL, Gearhart JP, Berkovitz B, Brown TJ, et al. Complete androgen insensitivity syndrome. Long-term medical, surgical, and psychosexual outcome. J Clin Endocrinol Metabol. 2000;85:2664-9.
30. Diamond M, Sigmundson HK. Sex reassignment at birth: long-term review and clinical implications. Arch Pediatr Adolesc Med. 1997;151:298-304.
31. Bradley SJ, Oliver GD, Chernick AB, Zucker KJ. Experiment of nurture: ablatio penis at 2 months, sex reasignment at 7 months and a psychosexual follow-up in young adulthood. Pediatrics. 1998;102(1):e9.
32. Dessens AB, Slijper FME, Drop SLS. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav. 2005;34:389-97.
33. Meyer-Bahlburg HFL, Gruen RS, New MI, Bell JJ, Morishima A, Shimshi M, et al. Gender change from female to male in classical congenital adrenal hyperplasia. Horm Behav. 1996;30:319-32.
34. Slijper FME, Drop SLS, Molenaar JC, Keizer-Schrama SMPFM. Long-term psychological evaluation of intersex children. Arch Sex Behav. 1998;27:125-44.
35. Cohen-Kettenis PT. Gender change in 46, XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005;34:399-410.
36. Zucker KJ, Bradley SJ, Oliver G, Blake J, Fleming S, Hood J. Psychosexual development of women with congenital adrenal hyperplasia. Horm Behav. 1996;30:300-18.
37. Pasterski VL, Zucker KJ, Hindmarsh PC, Hughes IA, Acerini CL, Spencer D, et al. Increased cross-gender identification independent of gender role behavior in girls with congenital adrenal hyperplasia: results from a standardized assessment of 4-11-year-old children. Arch Sex Behav. 2015; in press.
38. Berenbaum SA, Bailey JM. Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia. J Clin Endocrinol Metabol. 2003;88:1102-6.
39. Mazur T. Gender dysphoria and gender change in androgen insensitivity or micropenis. Arch Sex Behav. 2005;34:411-21.
40. Mathews GA, Fane BA, Conway GS, Brook C, Hines M. Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure. Horm Behav. 2009;55:285-91.
41. Berenbaum SA, Resnick SM. Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia. Psychoneuroendocrinology. 1997;22:505-15.
42. Pasterski VL, Hindmarsh P, Geffner M, Brook C, Brain C, Hines M. Increased aggression and activity level in 3- to 11-year-old girls with congenital adrenal hyperplasia (CAH). Horm Behav. 2007;52:368-74.
43. Ehrhardt AA, Baker SW. Fetal androgens, human central nervous system differentiation, and behavior sex differences. In: Friedman RC, Richart RM, van de Wiele RL, editors. Sex differences in behavior. New York: Wiley; 1974. p. 33-52.
44. Ehrhardt AA, Epstein R, Money J. Fetal androgens and female gender identity in the early-treated adrenogenital syndrome. Johns Hopkins Med J. 1968;122:160-7.
45. Reinisch JM. Prenatal exposure to synthetic progestins increases potential for aggression in humans. Science. 1981;211:1171-3.
46. Berenbaum SA, Korman Bryk KL, Beltz AM. Early androgen effects on spatial and mechanical abilities: evidence from congenital adrenal hyperplasia. Behav Neurosci. 2012;126:86-96.
47. Resnick SM, Berenbaum SA, Gottesman II, Bouchard T. Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia. Dev Psychol. 1986;22:191-8.
48. Malouf MA, Migeon CJ, Carson KA, Pertrucci L, Wisniewski AB. Cognitive outcome in adult women affected by congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res. 2006;65:142-50.
49. Hines M, Fane BA, Pasterski VL, Mathews GA, Conway GS, Brook C. Spatial abilities following prenatal androgen abnormality: targeting and mental rotations performance in individuals with congenital adrenal hyperplasia (CAH). Psychoneuroendocrinology. 2003;28:1010-26.
50. Helleday J, Bartfai A, Ritzen EM, Forsman M. General intelligence and cognitive profile in women with congenital adrenal hyperplasia (CAH). Psychoneuroendocrinology. 1994;19:343-56.
51. Baker SW, Ehrhardt AA. Prenatal androgen, intelligence and cognitive sex differences. In: Friedman RC, Richart RN, Vande Wiele RL, editors. Sex differences in behavior. New York: Wiley; 1974. p. 53-76.
52. Knickmeyer R, Baron-Cohen S, Fane B, Wheelwright S, Mathews GA, Conway GS, et al. Androgens and autistic traits: a study of individuals with congenital adrenal hyperplasia. Horm Behav. 2006;50:148-53.
53. Hines M, Golombok S, Rust J, Johnston K, Golding J, The ALSPAC Study Team. Testosterone during pregnancy and childhood gender role behavior: a longitudinal population study. Child Dev. 2002;73:1678-87.
54. Udry JR, Morris NM, Kovenock J. Androgen effects on women's gendered behaviour. J Biosoc Sci. 1995;27:359-68.
55. Rodeck CH, Gill D, Rosenberg DA, Collins WP. Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid. Prenat Diagn. 1985;5:175-81.
56. Gitau R, Adams D, Fisk NM, Glover V. Fetal plasma testosterone correlates positively with cortisol. Arch Dis Child Fetal Neonatal Ed. 2005;90:F166-9.
57. Auyeung B, Baron-Cohen S, Chapman E, Knickmeyer R, Taylor K, Hackett G, et al. Fetal testosterone predicts sexually differentiated childhood behavior in girls and in boys. Psychol Sci. 2009;20:144-8.
58. Knickmeyer R, Wheelwright S, Hackett G, Taylor K, Raggatt P, Baron-Cohen S. Gender-typed play and amniotic testosterone. Dev Psychobiol. 2005;41:517-28.
59. van de Beek C, Van Goozen SHM, Buitelaar JK, Cohen-Kettenis PT. Prenatal sex hormones (maternal and amniotic fluid) and gender-related play behavior in 13-month-old infants. Arch Sex Behav. 2009;38:6-15.
60. Grimshaw GM, Sitarenios G, Finegan JK. Mental rotation at 7 years: relations with prenatal testosterone levels and spatial play experiences. Brain Cogn. 1995;29:85-100.
61. Auyeung B, Knickmeyer R, Ashwin E, Taylor K, Hackett G, Baron-Cohen S. Effects of fetal testosterone on visuospatial ability. Arch Sex Behav. 2012;41:571-81.
62. Voyer D, Voyer S, Bryden MP. Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables. Psychol Bull. 1995;117:250-70.
63. Linn MC, Petersen AC. A meta-analysis of gender differences in spatial ability: implications for mathematics and science achievement. In: Hyde JS, Linn MC, editors. The Psychology of Gender: Advances through Meta-analysis. Baltimore: Johns Hopkins University; 1986. p. 67-101.
64. Lutchmaya S, Baron-Cohen S, Raggatt P. Foetal testosterone and vocabulary size in 18- and 24-month-old infants. Infant Behav Dev. 2002;24:418-42.
65. Lutchmaya S, Baron-Cohen S, Raggatt P. Foetal testosterone and eye contact in 12-month-old human infants. Infant Behav Dev. 2002;25:327-35.
66. Lutchmaya S. Foetal testosterone and social-communicative development. PhD Thesis, Department of Psychology, University of Cambridge. 2001.
67. Chapman E, Baron-Cohen S, Auyeung B, Knickmeyer R, Taylor K, Hackett G. Fetal testosterone and empathy: evidence from the empathy quotient (EQ) and the "reading the mind in the eyes" test. Soc Neurosci. 2006;1:135-48.
68. Knickmeyer R, Baron-Cohen S, Raggatt P, Taylor K, Hackett G. Fetal testosterone and empathy. Horm Behav. 2006;49:282-92.
69. Knickmeyer R, Baron-Cohen S, Raggatt P, Taylor K. Foetal testosterone, social relationships, and restricted interests in children. J Child Psychol Psychiatry. 2005;45:1-13.
70. Auyeung B, Baron-Cohen S, Chapman E, Knickmeyer R, Taylor K. Foetal testosterone and the child systemizing quotient. Eur J Endocrinol. 2006;155:123-30.
71. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G. Fetal testosterone and autistic traits. Br J Psychol. 2009;100:1-22.
72. Auyeung B, Ahluwalia J, Thomson L, Taylor K, Hackett G, O'Donell KJ, et al. Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age. Mol Autism. 2012;3:17.
73. Baron-Cohen S, Auyeung B, Norgaard-Pedersen B, Hougaard DM, Abdallah MW, Melgaard L, et al. Elevated fetal steroidogenic activity in autism. Mol Psychiatry. 2014;48:1-8.
74. Alexander GM, Peterson BS. Testing the prenatal hormone hypothesis of tic-related disorders: gender identity and gender role behavior. Dev Psychopathol. 2004;16:407-20.
75. Martel MM, Klump K, Nigg JT, Breedlove SM, Sisk CL. Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective. Horm Behav. 2009;55:465-79.
76. Culbert KM, Breedlove SM, Burt SA, Klump KL. Prenatal hormone exposure and risk for eating disorders. Arch Gen Psychiatry. 2008;65:329-36.
77. Raevuori A, Kaprio J, Hoek HW, Sihvola E, Rissanen A, Keski-Rahkonen A. Anorexia and bulimia nervosa in same-sex and opposite-sex twins: lack of an association with twin type in a nationwide study of Finnish twins. Am J Psychiatr. 2008;165:1604-10.
78. Lamminmaki A, Hines M, Kuiri-Hanninen T, Kilpelainen L, Dunkel L, Sankilampi U. Testosterone measured in infancy predicts subsequent sex-typed behavior in boys and in girls. Horm Behav. 2012;61:611-6.
79. Alexander GM, Wilcox T, Farmer ME. Hormone-behavior associations in early infancy. Horm Behav. 2009;56:498-502.
80. Alexander GM, Saenz J. Postnatal testosterone levels and temperament in early infancy. Arch Sex Behav. 2010;40:1287-92.
81. Collaer ML, Hines M. Human behavioral sex differences: a role for gonadal hormones during early development? Psychol Bull. 1995;118:55-107.
82. Cohen-Bendahan CCC, van de Beek C, Berenbaum SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev. 2005;29:353-84.