Spatial abilities contribute to life and occupational competencies, and certain spatial skills differ, on average, between males and females, typically favoring males when differences occur. Factors contributing to spatial skills could include prenatal as well as experiential/cultural influences, with biological and social influences likely interacting and difficult to disentangle. This meta-analysis examined the potential influence of prenatal androgen exposure on spatial skill by examining studies of patients with congenital adrenal hyperplasia (CAH). CAH involves elevated adrenal androgens prenatally, with overall androgen concentrations higher for females with CAH versus same-sex controls but with little overall difference between males with CAH versus controls. We hypothesized that, if androgens contribute prenatally to neurobehavioral development in humans as in many other species, females with CAH would show spatial enhancement versus control females, but with no definitive hypothesis for males. Meta-analysis of 12 studies examining overall spatial skill and three spatial subcategories failed to support enhanced spatial performance for females with CAH; males with CAH showed lower spatial ability compared to control males, at least for the category of overall spatial skill. Although statistical logic precludes accepting the null hypothesis for females, the meta-analysis failed to support the idea that prenatal exposure to androgens explains spatial gender/sex differences in humans. Alternative explanations for average gender/sex differences in some spatial tasks could include androgen exposure at other times, such as mini-puberty, or different social factors experienced by males and females. We also discuss possible explanations for the different outcomes seen in females versus males with CAH.
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Debate exists concerning whether to use the term “sex” or “gender,” with some arguing that “sex” should be reserved for biological distinctions and “gender” for social or cultural ones. Others contend that the distinction is irrelevant due to the intertwining of these factors. For a variety of reasons, including our inability to know the origins of most characteristics, we will typically use the terms “gender/sex” or “gender/sex difference” (see Hyde, Bigler, Joel, Tate, & van Anders, 2019).
Alexander, G. M. (2014). Postnatal testosterone concentrations and male social development. Frontiers in Endocrinology,5, 15. https://doi.org/10.3389/fendo.2014.00015.
Arnold, A. P. (2009). The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Hormones and Behavior,55, 570–578. https://doi.org/10.1016/j.yhbeh.2009.03.011.
Baker, S. K. W. (1993). An exploratory family study of IQ and specific cognitive abilities in classical congenital adrenal hyperplasia: Examined by family, genetic, and salt wasting subgroups. Unpublished doctoral dissertation, Columbia University, New York.
Baker, S. W., & Ehrhardt, A. A. (1974). Prenatal androgen, intelligence and cognitive sex differences. In R. C. Friedman, R. M. Richart, & R. L. Vande Wiele (Eds.), Sex differences in behavior (pp. 53–76). New York: Wiley.
Begg, C. B., & Mazumdar, M. (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics,50, 1088–1101.
Berenbaum, S. A., Bryk, K. L., & Beltz, A. M. (2012). Early androgen effects on spatial and mechanical abilities: Evidence from congenital adrenal hyperplasia. Behavioral Neuroscience,126, 86–96.
Berenbaum, S. A., Bryk, K. K., & Duck, S. C. (2010). Normal intelligence in female and male patients with congenital adrenal hyperplasia. International Journal of Pediatric Endocrinology. https://doi.org/10.1155/2010/853103.
Berenbaum, S. A., & Hines, M. (1992). Early androgens are related to childhood sex-typed toy preferences. Psychological Science,3, 203–206.
Borenstein, M., Hedges, L., Higgins, J., & Rothstein, H. (2005). Comprehensive meta-analysis, version 2. Englewood, NJ: Biostat. www.meta-analysis.com.
Borenstein, M., Hedges, L., Higgins, J., & Rothstein, H. (2009). Introduction to meta-analysis. Chichester, UK: Wiley.
Browne, W. V., Hindmarsh, P. C., Pasterski, V., Hughes, I. A., Acerini, C. L., Spencer, D., & Hines, M. (2015). Working memory performance is reduced in children with congenital adrenal hyperplasia. Hormones and Behavior,67, 83–88.
Carr, B. R. (1998). Disorders of the ovaries and female reproductive tract. In J. D. Wilson, D. W. Foster, H. M. Kronenberg, & P. R. Larsen (Eds.), Williams textbook of endocrinology (9th ed., pp. 751–817). Philadelphia: Saunders.
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Lawrence Erlbaum.
Collaer, M. L., Hindmarsh, P. C., Pasterski, V., Fane, B. A., & Hines, M. (2016). Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance. Psychoneuroendocrinology,64, 164–173. https://doi.org/10.1016/j.psyneuen.2015.11.010.
Constantinescu, M., Moore, D. S., Johnson, S. P., & Hines, M. (2018). Early contributions to infants’ mental rotation abilities. Developmental Science,21, e12613. https://doi.org/10.1111/desc.12613.
Dittmann, R. W., Kappes, M. H., & Kappes, M. E. (1993). Cognitive functioning in female patients with 21-hydroxylase deficiency. European Child and Adolescent Psychiatry,2, 34–43. https://doi.org/10.1007/BF02098828.
Dittmann, R. W., Kappes, M. H., Kappes, M. E., Börger, D., Stegner, H., Willig, R. H., & Wallis, H. (1990). Congenital adrenal hyperplasia I: Gender-related behavior and attitudes in female patients and sisters. Psychoneuroendocrinology,15, 401–420.
Dubois, J., Dehaene-Lambertz, G., Kulikova, S., Poupon, C., Huppi, P. S., & Hertz-Pannier, L. (2014). The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants. Neuroscience,276, 48–71. https://doi.org/10.1016/j.neuroscience.2013.12.044.
Duval, S., & Tweedie, R. (2000a). A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. Journal of the American Statistical Association,95, 89–98. https://doi.org/10.1080/01621459.2000.10473905.
Duval, S., & Tweedie, R. (2000b). Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics,56, 455–463.
El-Maouche, D., Arlt, W., & Merke, D. P. (2017). Congenital adrenal hyperplasia. Lancet,390(10108), 2194–2210. https://doi.org/10.1016/s0140-6736(17)31431-9.
Gilligan, K. A., Flouri, E., & Farran, E. K. (2017). The contribution of spatial ability to mathematics achievement in middle childhood. Journal of Experimental Child Psychology,163, 107–125. https://doi.org/10.1016/j.jecp.2017.04.016.
Halpern, D. F., Benbow, C. P., Geary, D. C., Gur, R. C., Hyde, J. S., & Gernsbacher, M. A. (2007). The science of sex differences in science and mathematics. Psychological Science in the Public Interest,8, 1–51.
Halpern, D. F., & Collaer, M. L. (2005). Sex differences in visuospatial abilities: More than meets the eye. In P. Shah & M. Akira (Eds.), The Cambridge handbook of visuospatial thinking (pp. 170–212). New York: Cambridge University Press.
Hamed, S. A., Metwalley, K. A., & Farghaly, H. S. (2018). Cognitive function in children with classic congenital adrenal hyperplasia. European Journal of Pediatrics,177(11), 1633–1640. https://doi.org/10.1007/s00431-018-3226-7.
Hampson, E., & Rovet, J. F. (2015). Spatial function in adolescents and young adults with congenital adrenal hyperplasia: Clinical phenotype and implications for the androgen hypothesis. Psychoneuroendocrinology,54, 60–70. https://doi.org/10.1016/j.psyneuen.2015.01.022.
Hampson, E., Rovet, J. F., & Altmann, D. (1998). Spatial reasoning in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Developmental Neuropsychology,14, 299–320.
Healy, W. (1914). A Pictorial Completion Test. Psychological Review,21, 189–203. https://doi.org/10.1037/h0075712.
Hedges, L. V. (1992). Modeling publication selection effects in meta-analysis. Statistical Science,7, 246–255.
Helleday, J., Bartfai, A., Ritzen, E. M., & Forsman, M. (1994). General intelligence and cognitive profile in women with congenital adrenal hyperplasia (CAH). Psychoneuroendocrinology,19, 343–356.
Hier, D. B., & Crowley, W. F., Jr. (1982). Spatial ability in androgen-deficient men. New England Journal of Medicine,306, 1202–1205.
Hines, M. (2004). Brain gender. Oxford: Oxford University Press.
Hines, M. (2011). Gender development and the human brain. Annual Review of Neuroscience,34, 67–86.
Hines, M. (2015). Gendered development. In M. E. Lamb & R. M. Lerner (Eds.), Handbook of child psychology and developmental science (7th ed., Vol. 3, pp. 842–887). Hoboken, NJ: Wiley.
Hines, M., Constantinescu, M., & Spencer, D. (2015). Early androgen exposure and human gender development. Biology of Sex Differences,6, 3. https://doi.org/10.1186/s13293-015-0022-1.
Hines, M., Fane, B. A., Pasterski, V. L., Mathews, G. A., Conway, G. S., & Brook, C. (2003). Spatial abilities following prenatal androgen abnormality: Targeting and mental rotations performance in individuals with congenital adrenal hyperplasia. Psychoneuroendocrinology,28, 1010–1026.
Hines, M., Golombok, S., Rust, J., Johnston, K. J., & Golding, J. (2002). Testosterone during pregnancy and gender role behavior of preschool children: A longitudinal, population study. Child Development,73, 1678–1687. https://doi.org/10.1111/1467-8624.00498.
Hines, M., Pasterski, V., Spencer, D., Neufeld, S., Patalay, P., Hindmarsh, P. C., … Acerini, C. L. (2016a). Prenatal androgen exposure alters girls’ responses to information indicating gender-appropriate behaviour. Philosophical Transactions of the Royal Society of London. Series B, Biological sciences, 371(1688), 20150125. https://doi.org/10.1098/rstb.2015.0125.
Hines, M., Spencer, D., Kung, K. T., Browne, W. V., Constantinescu, M., & Noorderhaven, R. M. (2016b). The early postnatal period, mini-puberty, provides a window on the role of testosterone in human neurobehavioural development. Current Opinion in Neurobiology,38, 69–73. https://doi.org/10.1016/j.conb.2016.02.008.
Hirvikoski, T., Nordenström, A., Lindholm, T., Lindblad, F., Ritzén, E. M., Wedell, A., & Lajic, S. (2007). Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone. Journal of Clinical Endocrinology and Metabolism,92, 542–548. https://doi.org/10.1210/jc.2006-1340.
Hyde, J. S. (2005). The gender similarities hypothesis. American Psychologist,60(6), 581–592.
Hyde, J. S., Bigler, R. S., Joel, D., Tate, C. C., & van Anders, S. M. (2019). The future of sex and gender in psychology: Five challenges to the gender binary. American Psychologist,74, 171–193. https://doi.org/10.1037/amp0000307.
Inozemtseva, O., Matute, E., & Juárez, J. (2008). Learning disabilities spectrum and sexual dimorphic abilities in girls with congenital adrenal hyperplasia. Journal of Child Neurology,23, 862–869. https://doi.org/10.1177/0883073808315618.
Ioannidis, J. P. A., & Trikalinos, T. A. (2007). The appropriateness of asymmetry tests for publication bias in meta-analyses: A large survey. Canadian Medical Association Journal,176, 1091–1096. https://doi.org/10.1503/cmaj.060410.
Isgor, C., & Sengelaub, D. R. (2003). Effects of neonatal gonadal steroids on adult CA3 pyramidal neuron dendritic morphology and spatial memory in rats. Journal of Neurobiology,55, 179–190. https://doi.org/10.1002/neu.10200.
Johannsen, T. H., Ripa, C. P. L., Reinisch, J. M., Schwartz, M., Mortensen, E. L., & Main, K. M. (2006). Impaired cognitive function in women with congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism,91, 1376–1381. https://doi.org/10.1210/jc.2005-1959.
Kelso, W. M., Nicholls, M. E. R., Warne, G. L., & Zacharin, M. (2000). Cerebral lateralization and cognitive functioning in patients with congenital adrenal hyperplasia. Neuropsychology,14, 370–378.
Kuiri-Hänninen, T., Sankilampi, U., & Dunkel, L. (2014). Activation of the hypothalamic-pituitary-gonadal axis in infancy: Minipuberty. Hormone Research in Paediatrics,82, 73–80. https://doi.org/10.1159/000362414.
Kung, K. T. F., Browne, W. V., Constantinescu, M., Noorderhaven, R. M., & Hines, M. (2016). Early postnatal testosterone predicts sex-related differences in early expressive vocabulary. Psychoneuroendocrinology,68, 111–116. https://doi.org/10.1016/j.psyneuen.2016.03.001.
Lamminmäki, A., Hines, M., Kuiri-Hänninen, T., Kilpeläinen, L., Dunkel, L., & Sankilampi, U. (2012). Testosterone measured in infancy predicts subsequent sex-typed behavior in boys and in girls. Hormones and Behavior,61, 611–616.
Lau, J., Ioannidis, J. P., & Schmid, C. H. (1997). Quantitative synthesis in systematic reviews. Annals of Internal Medicine,127, 820–826.
Linn, M. C., & Petersen, A. C. (1985). Emergence and characterization of sex differences in spatial ability: A meta-analysis. Child Development,56, 1479–1498.
Lipsey, M. W., & Wilson, D. B. (2001). Practical meta-analysis (Vol. 49). Thousand Oaks, CA: Sage.
Maccoby, E. E., & Jacklin, C. N. (1974). The psychology of sex differences. Stanford, CA: Stanford University Press.
Malouf, M. A., Migeon, C. J., Carson, K. A., Petrucci, L., & Wisniewski, A. B. (2006). Cognitive outcome in adult women affected by congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hormone Research,65, 142–150. https://doi.org/10.1159/000091793.
Martin, C. L., & Ruble, D. N. (2010). Patterns of gender development. Annual Review of Psychology,61, 353–381.
McGuire, L. S., & Omenn, G. S. (1975). Congenital adrenal hyperplasia. I. Family studies of IQ. Behavior Genetics,5, 165–173.
McGuire, L. S., Ryan, K. O., & Omenn, G. S. (1975). Congenital adrenal hyperplasia. II. Cognitive and behavioral studies. Behavior Genetics,5, 175–188.
Meaney, M. J. (1988). The sexual differentiation of social play. Trends in Neurosciences,11, 54–58. https://doi.org/10.1016/0166-2236(88)90164-6.
Merke, D. P., Fields, J. D., Keil, M. F., Vaituzis, A. C., Chrousos, G. P., & Giedd, J. N. (2003). Children with classic congenital adrenal hyperplasia have decreased amygdala volume: Potential prenatal and postnatal hormonal effects. Journal of Clinical Endocrinology and Metabolism,88, 1760–1765. https://doi.org/10.1210/jc.2002-021730.
Miller, W. L., & Auchus, R. J. (2011). The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews,32, 81–151.
Money, J., & Lewis, V. (1966). IQ, genetics and accelerated growth: Adrenogenital syndrome. Bulletin of the Johns Hopkins Hospital,118, 365–373.
Nass, R., & Baker, S. (1991). Learning disabilities in children with congenital adrenal hyperplasia. Journal of Child Neurology,6, 306–312.
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. Journal of Clinical Endocrinology and Metabolism,87, 5119–5124. https://doi.org/10.1210/jc.2001-011531.
Nuttall, R. L., Casey, M. B., & Pezaris, E. (2005). Spatial ability as a mediator of gender differences on mathematics tests. In A. M. Gallagher & J. C. Kaufman (Eds.), Gender differences in mathematics: An integrative psychological approach (pp. 121–142). Cambridge: Cambridge University Press.
Pang, S., Levine, L. S., Cederqvist, L. L., Fuentes, M., Riccardi, V. M., Holcombe, J. H., & New, M. I. (1980). Amniotic fluid concentrations of steroids in fetuses with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and in anencephalic fetuses. Journal of Clinical Endocrinology and Metabolism,51, 223–229.
Pang, S., Levine, L. S., Chow, D. M., Faiman, C., & New, M. I. (1979). Serum androgen concentrations in neonates and young infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinical Endocrinology,11, 373–384.
Pasterski, V., Acerini, C. L., Dunger, D. B., Ong, K. K., Hughes, I. A., Thankamony, A., & Hines, M. (2015). Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys. Hormones and Behavior,69, 98–105. https://doi.org/10.1016/j.yhbeh.2015.01.002.
Pazzaglia, F., & Moè, A. (2013). Cognitive styles and mental rotation ability in map learning. Cognitive Processing,14, 391–399. https://doi.org/10.1007/s10339-013-0572-2.
Perlman, S. M. (1973). Cognitive abilities of children with hormone abnormalities: Screening by psychoeducational tests. Journal of Learning Disabilities,6, 21–29.
Puts, D. A., McDaniel, M. A., Jordan, C. L., & Breedlove, S. M. (2008). Spatial ability and prenatal androgens: Meta-analyses of congenital adrenal hyperplasia and digit ratio (2D:4D) studies. Archives of Sexual Behavior,37, 100–111.
Resnick, S. M. (1982). Psychological functioning in individuals with congenital adrenal hyperplasia: Early hormonal influences on cognition and personality. Unpublished doctoral dissertation, University of Minnesota, Minneapolis.
Resnick, S. M., Berenbaum, S. A., Gottesman, I. I., & Bouchard, T. J. (1986). Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia. Developmental Psychology,22, 191–198.
Roof, R. L. (1993). Neonatal exogenous testosterone modifies sex difference in radial arm and Morris water maze performance in prepubescent and adult rats. Behavioural Brain Research,53(1–2), 1–10.
Roof, R. L., & Havens, M. D. (1992). Testosterone improves maze performance and induces development of a male hippocampus in females. Brain Research,572, 310–313.
Ruble, D. N., Taylor, L. J., Cyphers, L., Greulich, F. K., Lurye, L. E., & Shrout, P. E. (2007). The role of gender constancy in early gender development. Child Development,78, 1121–1136. https://doi.org/10.1111/j.1467-8624.2007.01056.x.
Schaadt, G., Hesse, V., & Friederici, A. D. (2015). Sex hormones in early infancy seem to predict aspects of later language development. Brain and Language,141, 70–76. https://doi.org/10.1016/j.bandl.2014.11.015.
Somajni, F., Sovera, V., Albizzati, A., Russo, G., Peroni, P., Seragni, G., & Lenti, C. (2011). Neuropsychological assessment in prepubertal patients with congenital adrenal hyperplasia: preliminary study. Minerva Pediatrica,63(1), 1–9.
Sorby, S., Veurink, N., & Streiner, S. (2018). Does spatial skills instruction improve STEM outcomes? The answer is ‘yes’. Learning and Individual Differences,67, 209–222. https://doi.org/10.1016/j.lindif.2018.09.001.
Speiser, P. W., Arlt, W., Auchus, R. J., Baskin, L. S., Conway, G. S., Merke, D. P., & White, P. C. (2018). Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism,103, 4043–4088. https://doi.org/10.1210/jc.2018-01865.
Stieff, M., & Uttal, D. (2015). How much can spatial training improve STEM achievement? Educational Psychology Review,27, 607–615. https://doi.org/10.1007/s10648-015-9304-8.
Uttal, D. H., Meadow, N. G., Tipton, E., Hand, L. L., Alden, A. R., Warren, C., & Newcombe, N. S. (2013). The malleability of spatial skills: A meta-analysis of training studies. Psychological Bulletin,139, 352–402. https://doi.org/10.1037/a0028446.
Voyer, D., & Jansen, P. (2017). Motor expertise and performance in spatial tasks: A meta-analysis. Human Movement Science,54, 110–124. https://doi.org/10.1016/j.humov.2017.04.004.
Voyer, D., Voyer, S., & Bryden, M. P. (1995). Magnitude of sex differences in spatial abilities: A meta-analysis and consideration of critical variables. Psychological Bulletin,117, 250–270.
Voyer, D., Voyer, S., & Saint-Aubin, J. (2017). Sex differences in visual-spatial working memory: A meta-analysis. Psychomics Bulletin and Review,24, 307–334. https://doi.org/10.3758/s13423-016-1085-7.
Wenzel, U., Schneider, M., Zachmann, M., Knorr-Mürset, G., Weber, A., & Prader, A. (1978). Intelligence of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, their parents and unaffected siblings. Helvetica Paediatrica Acta,33, 11–16.
White, P. C., & Speiser, P. W. (2000). Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocrine Reviews,21, 245–291. https://doi.org/10.1210/er.21.3.245.
Williams, C. L., Barnett, A. M., & Meck, W. H. (1990). Organizational effects of early gonadal secretions on sexual differentiation in spatial memory. Behavioral Neuroscience,104, 84–97.
Witchel, S. F. (2017). Congenital adrenal hyperplasia. Journal of Pediatric and Adolescent Gynecology,30, 520–534. https://doi.org/10.1016/j.jpag.2017.04.001.
Wong, W. I., & Hines, M. (2015). Preferences for pink and blue: The development of color preferences as a distinct gender-typed behavior in toddlers. Archives of Sexual Behavior,44, 1243–1254. https://doi.org/10.1007/s10508-015-0489-1.
Wright, R., Thompson, W. L., Ganis, G., Newcombe, N. S., & Kosslyn, S. M. (2008). Training generalized spatial skills. Psychonomics Bulletin and Review,15, 763–771. https://doi.org/10.3758/PBR.15.4.763.
Marcia Collaer received support from the Middlebury College Research Leave Program; the A. Barton Hepburn Endowed Professorship; and an Overseas Fellowship from Churchill College, University of Cambridge. Melissa Hines received research support from the United States Public Health Service (HD081720). We thank Elise Park, Middlebury College, for her work extracting data and computing summary statistics for the meta-analysis.
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Collaer, M.L., Hines, M. No Evidence for Enhancement of Spatial Ability with Elevated Prenatal Androgen Exposure in Congenital Adrenal Hyperplasia: A Meta-Analysis. Arch Sex Behav (2020). https://doi.org/10.1007/s10508-020-01645-7
- Spatial ability
- Visuospatial ability
- Congenital adrenal hyperplasia (CAH)
- Gender differences
- Sex differences