The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Androgens; Brain function; Brain structure; Complete androgen insensitivity syndrome; Estrogens; Magnetic resonance imaging; Sex differences; Sexual development

Abstract :

[en] Men and women differ, not only in their anatomy but also in their behavior. Research using animal models has convincingly shown that sex differences in the brain and behavior are induced by sex hormones during a specific, hormone-sensitive period during early development. Thus, male-typical psychosexual characteristics seem to develop under the influence of testosterone, mostly acting during early development. By contrast, female-typical psychosexual characteristics may actually be organized under the influence of estradiol during a specific prepubertal period. The sexual differentiation of the human brain also seems to proceed predominantly under the influence of sex hormones. Recent studies using magnetic resonance imaging have shown that several sexually differentiated aspects of brain structure and function are female-typical in women with complete androgen insensitivity syndrome (CAIS), who have a 46 XY karyotype but a female phenotype due to complete androgen resistance, suggesting that these sex differences most likely reflect androgen action, although feminizing effects of estrogens or female-typical socialization cannot be ruled out. By contrast, some male-typical neural characteristics were also observed in women with CAIS suggesting direct effects of sex chromosome genes in the sexual differentiation of the human brain. In conclusion, the sexual differentiation of the human brain is most likely a multifactorial process including both sex hormone and sex chromosome effects, acting in parallel or in combination.

Disciplines :

Neurosciences & behavior

Author, co-author :

Bakker, Julie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau

Language :

English

Title :

The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Publication date :

2019

Journal title :

Current Topics in Behavioral Neurosciences

ISSN :

1866-3370

eISSN :

1866-3389

Publisher :

Springer, Germany

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 April 2019

Statistics

Number of views

772 (15 by ULiège)

Number of downloads

1704 (13 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Boehmer, A.L., Brüggenwirth, H., van Assendelft, C., Otten, B.J., Verleun-Mooijman, M.C., Niermeijer, M.F., Brunner, H.G., Drop, S.L., Genotype versus phenotype in families with androgen insensitivity syndrome (2001) J Clin Endocrinol Metab, 86, pp. 4151-4160
Breedlove, S.M., Prenatal influences on human sexual orientation: Expectations versus data (2017) Arch Sex Behav, 46, pp. 1583-1592
Brock, O., Douhard, Q., Baum, M.J., Bakker, J., Reduced prepubertal expression of progesterone receptor in the hypothalamus of female aromatase knockout mice (2010) Endocrinology, 151, pp. 1814-1821
Brock, O., Baum, M.J., Bakker, J., The development of female sexual behavior requires prepubertal estradiol (2011) J Neurosci, 31, pp. 5574-5578
Brunner, F., Fliegner, M., Krupp, K., Rall, K., Brucker, S., Richter-Appelt, H., Gender role, gender identity and sexual orientation in CAIS (“XY-women”) compared with subfertile and infertile 46,XX women (2016) J Sex Res, 53, pp. 109-124
Butler, T., Imperato-McGinley, J., Pan, H., Voyer, D., Cordero, J., Zhu, Y.-S., Stern, E., Silbersweig, D., Sex differences in mental rotation: Top-down versus bottom-up processing (2006) Neuroimage, 32, pp. 445-456
Byne, W., Tobet, S., Mattiace, L.A., Lasco, M.S., Kemether, E., Edgar, M.A., Morgello, S., Jones, L.B., The interstitial nuclei of the human anterior hypothalamus: An investigation of variation with sex, sexual orientation, and HIV status (2001) Horm Behav, 40, pp. 86-92
Carrel, L., Willard, H.F., X-inactivation profile reveals extensive variability in X-linked gene expression in females (2005) Nature, 434, pp. 400-404
Carrel, L., Cottle, A.A., Goglin, K.C., Willard, H.F., A first-generation X-inactivation profile of the human X chromosome (1999) Proc Natl Acad Sci U S A, 96, pp. 14440-14444
Chang, S.C., Tucker, T., Thorogood, N.P., Brown, C.J., Mechanisms of X-chromosome inactivation (2006) Front Biosci, 11, pp. 852-866
Chou, K.-H., Cheng, Y., Chen, I.-Y., Lin, C.-P., Chu, W.-C., Sex-linked white matter microstructure of the social and analytic brain (2011) Neuroimage, 54, pp. 725-733
Collaer, M.L., Hines, M., Human behavioral sex differences: A role for gonadal hormones during early development? (1995) Psychol Bull, 118, pp. 55-107
Connor, J.M., Serbin, L.A., Behaviorally based masculine-and feminine-activity-preference scales for preschoolers: Correlates with other classroom behaviors and cognitive tests (1977) Child Dev, 48, pp. 1411-1416
Cools, M., Drop, S.L.S., Wolffenbuttel, K.P., Oosterhuis, J.W., Looijenga, L.H.J., Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers (2006) Endocr Rev, 27, pp. 468-484
Corre, C., Friedel, M., Vousden, D.A., Metcalf, A., Spring, S., Qiu, L.R., Lerc, J.P., Palmert, M.R., Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation of the Four Core Genotype mouse model (2016) Brain Struct Funct, 221, pp. 997-1016
Cosgrove, K.P., Mazure, C.M., Staley, J.K., Evolving knowledge of sex differences in brain structure, function, and chemistry (2007) Biol Psychiatry, 62, pp. 847-855
Davis, H., An active process in cochlear mechanics (1983) Hear Res, 9, pp. 79-90
Davis, S.M., Rogol, A.D., Ross, J.L., Testis development and fertility potential in boys with klinefelter syndrome (2015) Endocrinol Metab Clin N Am, 44, pp. 843-865
de Vries, G.J., Rissman, E.F., Simerly, E.B., Yang, L.Y., Scordalakes, E.M., Auger, C.J., Swain, A., Arnold, A.P., A model system for sex chromosome effects on sexually dimorphic neural and behavioral traits (2002) J Neurosci, 22, pp. 9005-9014
Delisi, L.E., Maurizio, A.M., Svetina, C., Ardekani, B., Szulc, K., Nierenberg, J., Leonard, J., Harvey, P.D., Klinefelter’s syndrome (XXY) as a genetic model for psychotic disorders (2005) Am J Med Genet B Neuropsychiatr Genet, 135B, pp. 15-23
Dewing, P., Chiang, C.W.K., Sinchak, K., Sim, H., Fernagut, P.-O., Kelly, S., Chesselet, M.-F., Vilain, E., Direct regulation of adult brain function by the male specific factor SRY (2006) Curr Biol, 16, pp. 415-420
Disteche, C.M., Dosage compensation of the sex chromosomes (2012) Annu Rev Genet, 46, pp. 537-560
Doehnert, U., Bertelloni, S., Werner, R., Dati, E., Hiort, O., Characteristic features of reproductive hormone profiles in late adolescent and adult females with complete androgen insensitivity syndrome (2015) Sex Dev, 9, pp. 69-74
Dörner, G., Neuroendocrine response to estrogen and brain differentiation in heterosexuals, homosexuals, and transsexuals (1988) Arch Sex Behav, 17, pp. 57-75
Downey, J., Ehrhardt, A.A., Gruen, R., Bell, J.J., Morishima, A., Psychopathology and social functioning in women with Turner syndrome (1989) J Nerv Ment Dis, 177, pp. 191-201
Feder, H.H., Whalen, R.E., Feminine behavior in neonatally castrated and estrogen-treated male rats (1964) Science, 147, pp. 306-307
Feng, J., Spence, I., Pratt, J., Playing an action video game reduces gender differences in spatial cognition (2007) Psychol Sci, 18, pp. 850-855
Finkelstein, J.S., Lee, H., Burnett-Bowie, S.A., Pallais, J.C., Yu, E.W., Borges, L.F., Jones, B.F., Leder, B.Z., Gonadal steroids and body composition, strength, and sexual function in men (2013) N Engl J Med, 369, pp. 1011-1022
Garcia-Falgueras, A., Swaab, D.F., A sex difference in the hypothalamic uncinate nucleus: Relationship to gender identity (2008) Brain, 131, pp. 3132-3146
Gizewski, E.R., Krause, E., Wanke, I., Forsting, M., Senf, W., Gender-specific cerebral activation during cognitive tasks using functional MRI: Comparison of women in mid-luteal phase and men (2006) Neuroradiology, 48, pp. 14-20
Gizewski, E.R., Krause, E., Schlamann, M., Happich, F., Ladd, M.E., Forsting, M., Senf, W., Specific cerebral activation due to visual erotic stimuli in male-to-female transsexuals compared with male and female controls: An fMRI study (2009) J Sex Med, 6, pp. 440-448
Gong, G., He, Y., Evans, A.C., Brain connectivity: Gender makes a difference (2011) Neuroscientist, 17, pp. 575-591
Grady, K.L., Phoenix, C.H., Young, W.C., Role of the developing rat testis in differentiation of the neural tissues mediating mating behavior (1965) J Comp Physiol Psychol, 59, pp. 176-182
Halari, R., Hines, M., Kumari, V., Mehrotra, R., Wheeler, M., Ng, V., Sharma, T., Sex differences and individual differences in cognitive performance and their relationship to endogenous gonadal hormones and gonadotropins (2005) Behav Neurosci, 119, pp. 104-117
Hamann, S., Herman, R.A., Nolan, C.L., Wallen, K., Men and women differ in amygdala response to visual sexual stimuli (2004) Nat Neurosci, 7, pp. 411-416
Hamann, S., Stevens, J., Vick, J.H., Bryk, K., Quigley, C.A., Berenbaum, S.A., Wallen, K., Brain responses to sexual images in 46XY, women with complete androgen insensitivity syndrome are female-typical (2014) Horm Behav, 66, pp. 724-730
Hare, L., Bernard, P., Sanchez, F.J., Baird, P.N., Vilain, E., Kennedy, T., Harley, V.R., Androgen receptor repeat length polymorphism associated with male-to-female transsexualism (2009) Biol Psychiatry, 65, pp. 93-96
Hausmann, M., Schoofs, D., Rosenthal, H.E.S., Jordan, K., Interactive effects of sex hormones and gender stereotypes on cognitive sex differences – a psychobiosocial approach (2009) Psychoneuroendocrinology, 34, pp. 389-401
Hier, D.B., Crowley, W.F., Spatial ability in androgen-deficient men (1982) N Engl J Med, 306, pp. 1202-1205
Hines, M., Ahmed, S.F., Hughes, I.A., Psychological outcomes and gender-related development in complete androgen insensitivity syndrome (2003) Arch Sex Behav, 32, pp. 93-101
Hines, M., Pasterski, V., Spencer, D., Neufeld, S., Patalay, P., Hindmarsh, P.C., Hughes, I.A., Acerini, C.L., Prenatal androgen exposure alters girls’ responses to information regarding gender-appropriate behaviour (2016) Philos Trans R Soc B Biol Sci, 371
Holzapfel, M., Barnea-Goraly, N., Eckert, M.A., Kesler, S.R., Reiss, A.L., Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in Turner syndrome (2006) J Neurosci, 26, pp. 7007-7013
Hönekopp, J., Watson, S., Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand (2010) Am J Hum Biol, 22, pp. 619-630
Hoppe, C., Fliessbach, K., Stausberg, S., Stojanovic, J., Trautner, P., Elger, C.E., Weber, B., A key role for experimental task performance: Effects of math talent, gender and performance on the neural correlates of mental rotation (2012) Brain Cogn, 78, pp. 14-27
Hsiao, P.W., Lin, D.L., Nakao, R., Chang, C., The linkage of Kennedy’s neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator (1999) J Biol Chem, 274, pp. 20229-20234
Hughes, I.A., Deeb, A., Androgen resistance (2006) Best Pract Res Clin Endocrinol Metab, 20, pp. 577-598
Hughes, I.A., Houk, C., Ahmed, S.F., Lee, P.A., Consensus statement on management of intersex disorders (2006) J Pediatr Urol, 2, pp. 148-162
Hughes, I.A., Davies, J.D., Bunch, T.I., Pasterski, V., Mastroyannopoulou, K., Macdougall, J., Androgen insensitivity syndrome (2012) Lancet, 380, pp. 1419-1428
Imperato-McGinley, J., Pichardo, M., Gautier, T., Voyer, D., Bryden, M.P., Cognitive abilities in androgen-insensitive subjects: Comparison with control males and females from the same kindred (1991) Clin Endocrinol, 34, pp. 341-347
Inano, S., Takao, H., Hayashi, N., Abe, O., Ohtomo, K., Effects of age and gender on white matter integrity (2011) AJNR am J Neuroradiol, 32, pp. 2103-2109
Irvine, R.A., Ma, H., Yu, M.C., Ross, R.K., Stallcup, M.R., Coetzee, G.A., Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length (2000) Hum Mol Genet, 9, pp. 267-274
Jordan, K., Wüstenberg, T., Heinze, H.J., Peters, M., Jäncke, L., Women and men exhibit different cortical activation patterns during mental rotation tasks (2002) Neuropsychologia, 40, pp. 2397-2408
Kemp, D.T., Stimulated acoustic emissions from within the human auditory system (1978) J Acoust Soc Am, 64, pp. 1386-1391
Kemp, D.T., Otoacoustic emissions: Concepts and origins (2008) Active Processes and Otoacoustic Emissions in Hearing, pp. 1-38. , Manley GA, Fay RR, Popper AN, Springer handbook of auditory research. Springer, New York
Koopman, P., Munsterberg, A., Capel, B., Vivian, N., Lovell-Badge, R., Expression of a candidate sex-determining gene during mouse testis differentiation (1990) Nature, 348, pp. 450-452
Kruijver, F.P., Zhou, J.N., Pool, C.W., Hofman, M.A., Gooren, L.J., Swaab, D.F., Male-to-female transsexuals have female neuron numbers in a limbic nucleus (2000) J Clin Endocrinol Metab, 85, pp. 2034-2041
Kucian, K., Loenneker, T., Dietrich, T., Martin, E., von Aster, M., Gender differences in brain activation patterns during mental rotation and number related cognitive tasks (2005) Psychol Sci, 47, pp. 112-131
Kuiri-Hänninen, T., Sankilampi, U., Dunkel, L., Activation of the hypothalamic-pituitary-gonadal axis in infancy: Minipuberty (2014) Horm Res Paediatr, 82, pp. 73-80
Lamprecht, S.A., Kohen, F., Ausher, J., Zor, U., Lindner, H.R., Hormonal stimulation of oestradiol-17 beta release from the rat ovary during early postnatal development (1976) J Endocrinol, 68, pp. 343-344
Lee, P.A., Nordenström, A., Houk, C.P., Ahmed, S.F., Auchus, R., Baratz, A., Baratz Dalke, K., Witchel, S., Global disorders of sex development update since 2006: Perceptions, approach and care (2016) Horm Res Paediatr, 85, pp. 158-180
Lentini, E., Kasahara, M., Arver, S., Savic, I., Sex differences in the human brain and the impact of sex chromosomes and sex hormones (2012) Cereb Cortex, 23, pp. 2322-2336
Lessov-Schlaggar, C.N., Reed, T., Swan, G.E., Krasnow, R.E., Decarli, C., Marcus, R., Holloway, L., Carmelli, D., Association of sex steroid hormones with brain morphology and cognition in healthy elderly men (2005) Neurology, 65, pp. 1591-1596
Levay, S., A difference in hypothalamic structure between heterosexual and homosexual men (1991) Science, 253, pp. 1034-1037
Linn, M.C., Petersen, A.C., Emergence and characterization of sex differences in spatial ability: A meta-analysis (1985) Child Dev, 56, pp. 1479-1498
Lombardo, M.V., Ashwin, E., Auyeung, B., Chakrabarti, B., Taylor, K., Hackett, G., Bullmore, E.T., Baron-Cohen, S., Fetal testosterone influences sexually dimorphic gray matter in the human brain (2012) J Neurosci, 32, pp. 674-680
Lutchmaya, S., Baron-Cohen, S., Raggatt, P., Knickmeyer, R., Manning, J.T., 2nd to 4th digit ratios, fetal testosterone and estradiol (2004) Early Hum Dev, 77, pp. 23-28
Maccoby, E.E., Jacklin, C.N., (1974) The Psychology of Sex Differences, , Stanford University Press, Palo Alto
Maguire, E.A., Woollett, K., Spiers, H.J., London taxi drivers and bus drivers: A structural MRI and neuropsychological analysis (2006) Hippocampus, 16, pp. 1091-1101
Maki, P.M., Rich, J.B., Shayna Rosenbaum, R., Implicit memory varies across the menstrual cycle: Estrogen effects in young women (2002) Neuropsychologia, 40, pp. 518-529
Masica, D.N., Money, J., Ehrhardt, A.A., Lewis, V.G., IQ, fetal sex hormones and cognitive patterns: Studies in the testicular feminizing syndrome of androgen insensitivity (1969) Johns Hopkins Med J, 124, pp. 34-43
Masica, D.N., Money, J., Ehrhardt, A.A., Fetal feminization and female gender identity in the testicular feminizing syndrome of androgen insensitivity (1971) Arch Sex Behav, 1, pp. 131-142
McFadden, D., Pasanen, E.G., Comparison of the auditory systems of heterosexuals and homosexuals: Click-evoked otoacoustic emissions (1998) Proc Natl Acad Sci U S A, 95, pp. 2709-2713
Melo, K.F.S., Mendonca, B.B., Billerbeck, A.E.C., Costa, E.M.F., Inacio, M., Sliva, F.A.Q., Leal, A.M.O., Arnhold, I.J.P., Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: Five novel mutations in the androgen receptor gene (2003) J Clin Endocrinol Metab, 88, pp. 3241-3250
Merke, D.P., Fields, J.D., Keil, M.F., Vaituzis, A.C., Chrousos, G.P., Giedd, J.N., Children with classic congenital adrenal hyperplasia have decreased amygdala volume: Potential prenatal and postnatal hormonal effects (2003) J Clin Endocrinol Metab, 88, pp. 1760-1765
Meyer-Bahlburg, H.F.L., Dolezal, C., Baker, S.W., New, M.I., Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess (2008) Arch Sex Behav, 37, pp. 85-99
Modi, D.N., Sane, S., Bhartiya, D., Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads (2003) Mol Hum Reprod, 9, pp. 219-225
Morris, J.A., Jordan, C.L., Breedlove, S.M., Sexual differentiation of the vertebrate nervous system (2004) Nat Neurosci, 7, pp. 1034-1039
Nagamani, M., McDonough, P.G., Ellegood, J.O., Mahesh, V.B., Maternal and amniotic fluid steroids throughout human pregnancy (1979) Am J Obstet Gynecol, 134, pp. 674-680
Pasterski, V.L., Geffner, M.E., Brain, C., Hindmarsh, P., Brook, C., Hines, M., Prenatal hormones and postnatal socialization by parents as determinants of male-typical toy play in girls with congenital adrenal hyperplasia (2005) Child Dev, 76, pp. 264-278
Paus, T., Nawaz-Khan, I., Leonard, G., Perron, M., Pike, G.B., Pitiot, A., Richer, L., Pausova, Z., Sexual dimorphism in the adolescent brain: Role of testosterone and androgen receptor in global and local volumes of grey and white matter (2010) Horm Behav, 57, pp. 63-75
Perrin, J.S., Hervé, P.-Y., Leonard, G., Perron, M., Pike, G.B., Pitiot, A., Richer, L., Paus, T., Growth of white matter in the adolescent brain: Role of testosterone and androgen receptor (2008) J Neuro-Oncol, 28, pp. 9519-9524
Peters, M., Laeng, B., Latham, K., Jackson, M., Zaiyouna, R., Richardson, C., A redrawn Vanden-berg and Kuse mental rotation test: Different versions and factors that affect performance (1995) Brain Cogn, 28, pp. 39-58
Pierpaoli, C., Basser, P.J., Toward a quantitative assessment of diffusion anisotropy (1996) Magn Reson Med, 36, pp. 893-906
Printzlau, F., Wolstencroft, J., Skuse, D.H., Cognitive, behavioral and neural consequences of sex chromosome aneuploidy (2017) J Neurosci Res, 95, pp. 311-319
Puts, D.A., McDaniel, M.A., Jordan, C.L., Breedlove, S.M., Spatial ability and prenatal androgens: Meta-analyses of congenital adrenal hyperplasia and digit ratio (2D:4D) studies (2008) Arch Sex Behav, 37, pp. 100-111
Raznahan, A., Lee, Y., Stidd, R., Long, R., Greenstein, D., Clasen, L., Addington, A., Giedd, J.N., Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence (2010) Proc Natl Acad Sci U S A, 107, pp. 16988-16993
Reyes, F.I., Boroditsky, R.S., Winter, J.S., Faiman, C., Studies on human sexual development. II. Fetal and maternal serum gonadotropin and sex steroid concentrations (1974) J Clin Endocrinol Metab, 38, pp. 612-617
Rolstad, S.G., Moller, A., Bryman, I., Boman, U.W., Sexual functioning and partner relationships in women with Turner syndrome: Some empirical data and theoretical considerations regarding sexual desire (2007) J Sex Marital Ther, 33, pp. 231-247
Ross, J.L., Roeltgen, D., Feuillan, P., Kushner, H., Cutler, G.B., Effects of estrogen on nonverbal processing speed and motor function in girls with Turner’s Syndrome (1998) J Clin Endocrinol Metab, 83, pp. 3198-3204
Ruigrok, A.N.V., Salimi-Khorshidi, G., Lai, M.-C., Baron-Cohen, S., Lombardo, M.V., Tait, R.J., Suckling, J., A meta-analysis of sex differences in human brain structure (2014) Neurosci Biobehav Rev, 39, pp. 34-50
Sacher, J., Neumann, J., Okon-Singer, H., Gotowiec, S., Villringer, A., Sexual dimorphism in the human brain: Evidence from neuroimaging (2013) Magn Reson Imaging, 31, pp. 366-375
Savic, I., Frisen, L., Manzouri, A., Nordenstrom, A., Lindén Hirschberg, A., Role of testosterone and Y chromosome genes for the masculinization of the human brain (2017) Hum Brain Mapp, 38, pp. 1801-1814
Schirmer, A., Zysset, S., Kotz, S.A., Yves von Cramon, D., Gender differences in the activation of inferior frontal cortex during emotional speech perception (2004) Neuroimage, 21, pp. 1114-1123
Schöning, S., Engelien, A., Kugel, H., Schäfer, S., Schiffbauer, H., Zwitserlood, P., Pletziger, E., Ohrann, P., Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones (2007) Neuropsychologia, 45, pp. 3203-3214
Schoonheim, M.M., Rueda Lopes, F.C., Pouwels, P.J.W., Polman, C.H., Barkhof, F., Geurts, J.J.G., Sex-specific extent and severity of white matter damage in multiple sclerosis: Implications for cognitive decline (2014) Hum Brain Mapp, 35, pp. 2348-2358
Seurinck, R., Vingerhoets, G., de Lange, F.P., Achten, E., Does egocentric mental rotation elicit sex differences? (2004) Neuroimage, 23, pp. 1440-1449
Shaeffer, A.T., Lange, E., Bondy, C.A., Sexual function in women with Turner syndrome (2008) J Womens Health, 17, pp. 27-33
Shephard, R.N., Metzler, J., Mental rotation of three-dimensional objects (1971) Science, 171, pp. 701-703
Shinur, A.W.K., Hampson, E., Sex and ear differences in spontaneous and click-evoked otoacoustic emissions in young adults (2011) Brain Cogn, 77, pp. 40-47
Swaab, D.F., Sexual differentiation of the brain and behavior (2007) Best Pract Res Clin Endocrinol Metab, 21, pp. 431-444
Swaab, D.F., Hofman, M.A., An enlarged suprachiasmatic nucleus in homosexual men (1990) Brain Res, 537, pp. 141-148
T’Sjoen, G., de Cuypere, G., Monstrey, S., Hoebeke, P., Freedman, F.K., Appari, M., Holterhus, P.-M., Cools, M., Male gender identity in complete androgen insensitivity syndrome (2011) Arch Sex Behav, 40, pp. 635-638
Tadokoro-Cuccaro, R., Hughes, I.A., Androgen insensitivity syndrome (2014) Curr Opin Endocrinol Diabetes Obes, 21, pp. 499-503
Takao, H., Hayashi, N., Ohtomo, K., Sex dimorphism in the white matter: Fractional anisotropy and brain size (2014) J Magn Reson Imaging, 39, pp. 917-923
Taziaux, M., Swaab, D.F., Bakker, J., Sex differences in the neurokinin B system in the human infundibular nucleus (2012) J Clin Endocrinol Metab, 97, pp. E2210-E2220
Taziaux, M., Staphorsius, A.S., Ghatei, M.A., Bloom, S.R., Swaab, D.F., Bakker, J., Kisspeptin expression in the human infundibular nucleus in relation to sex, gender identity, and sexual orientation (2016) J Clin Endocrinol Metab, 101, pp. 2380-2389
Thomsen, T., Hugdahl, K., Ersland, L., Barndon, R., Lundervold, A., Smievoll, A.I., Roscher, B.E., Sundberg, H., Functional magnetic resonance imaging (FMRI) study of sex differences in a mental rotation task (2000) Med Sci Monit, 6, pp. 1186-1196
van Hemmen, J., Veltman, D.J., Hoekzema, E., Cohen-Kettenis, P.T., Dessens, A.B., Neural activation during mental rotation in complete androgen insensitivity syndrome: The influence of sex hormones and sex chromosomes (2016) Cereb Cortex, 26, pp. 1036-1045
van Hemmen, J., Cohen-Kettenis, P.T., Steensma, T.D., Veltman, D.J., Bakker, J., Do sex differences in CEOAEs and 2D:4D ratios reflect androgen exposure? A study in women with complete androgen insensitivity syndrome (2017) Biol Sex Differ, 8
van Hemmen, J., Saris, I.M.J., Cohen-Kettenis, P.T., Veltman, D.J., Pouwels, P.J.W., Bakker, J., Sex differences in white matter microstructure in the human brain predominantly reflect differences in sex hormone exposure (2017) Cereb Cortex, 27, pp. 2994-3001
Ventura, T., Gomes, M.C., Pita, A., Neto, M.T., Taylor, A., Digit ratio (2D,4D) in newborns: Influences of prenatal testosterone and maternal environment (2013) Early Hum Dev, 89, pp. 107-112
Wallen, K., Hormonal influences on sexually differentiated behavior in nonhuman primates (2005) Front Neuroendocrinol, 26, pp. 7-26
Weiss, E., Siedentopf, C.M., Hofer, A., Deisenhammer, E.A., Hoptman, M.J., Kremser, C., Golaszewski, S., Delazer, M., Sex differences in brain activation pattern during a visuospatial cognitive task: A functional magnetic resonance imaging study in healthy volunteers (2003) Neurosci Lett, 344, pp. 169-172
Winter, J.S., Hughes, I.A., Reyes, F.I., Faiman, C., Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age (1976) J Clin Endocrinol Metab, 42, pp. 679-686
Wisniewski, A.B., Migeon, C.J., Meyer-Bahlburg, H.F., Gearhart, J.P., Berkovitz, G.D., Brown, T.R., Money, J., Complete androgen insensitivity syndrome: Long-term medical, surgical, and psychosexual outcome (2000) J Clin Endocrinol Metab, 85, pp. 2664-2669
Witte, A.V., Savli, M., Holik, A., Kasper, S., Lanzenberger, R., Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain (2010) Neuroimage, 49, pp. 1205-1212
Zachmann, M., Prader, A., Sobel, E.H., Crigler, J.F., Jr., Ritzen, E.M., Atares, M., Ferrandez, A., Pubertal growth in patients with androgen insensitivity: Indirect evidence for the importance of estrogens in pubertal growth of girls (1986) J Pediatr, 108, pp. 694-697
Zachs, J.M., Neuroimaging studies of mental rotation: A meta-analysis and review (2008) J Cogn Neurosci, 20, pp. 1-19
Zhou, J.N., Hofman, M.A., Gooren, L.J., Swaab, D.F., A sex difference in the human brain and its relation to transsexuality (1995) Nature, 378, pp. 68-70
Zitzmann, M., Weckesser, M., Schober, O., Nieschlag, E., Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal males under testosterone substitution (2001) Exp Clin Endocrinol Diabetes, 109, pp. 302-304