ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This meta-analysis of studies of classical CAH indicates that prenatal androgen exposure masculinizes and defeminizes play behavior in humans.

Comment: Sex differences in juvenile-play behavior have been documented across a number of animal species, including non-human primates and in humans. It is proposed that juvenile play allows the developing individual to practice skills that are important for survival and adult social roles. In humans, average sex differences in play appear early in life and persist throughout childhood. By 12 months of age, sex-typical toy preferences emerge and by 2-3 years, boys and girls seem to prefer same-sex playmates and sex-segregated play. By 3 years, sex differences in play become more apparent; boys engage in more rough-and tumble and competitive play, whilst girls tend to engage in more verbal and nurturant play. These sex differences persist across the entire childhood (1). Compared to other human behavioral sex-differences, the sex-typical toy play behavior has a large effect size. Sex differences in play behavior are dependent on prenatal and neonatal androgen exposure during critical periods of early fetal and neonatal life, when androgen concentrations in males exceed those in females. There is a linear and positive relationship between androgen exposure and level of male-typical play behavior (2, 3). Areas in the brain that are re-organized by androgen exposure and that might affect the behavioral differences are the sexually dimorphic nucleus of the pre-optic area in rats and rams, the Onuf’s nucleus in rhesus macaques, and the amygdala, all of which are larger in males than females.

This study is a review and meta-analysis of studies investigating sex-typical play behaviour, and the effects of prenatal androgen exposure using congenital adrenal hyperplasia (CAH) as a model system. The meta-analysis included 20 independent samples, in total 517 females with CAH, 556 control females, 176 males with CAH, and 259 control males. Consistently across all 7 male-typical and female-typical play outcomes (male/female play behavior, male/female toy preferences, male playmate preferences, male/female overall play behavior), there were large differences between control males and control females (Hedges’ gs =0.83-2.78), as well as between females with CAH and control females (Hedges’ gs =0.95-1.08). However, differences between males with CAH and control males were mostly negligible and were non-significant for 6 of the 7 outcomes (Hedges’ gs =0.04-0.27). Prader scores or CYP21A2 genotypes were not included as moderators since very few studies reported these parameters.

In summary, the results suggest that females with CAH are between control females and control males when it comes to toy-play behaviors. This supports the notion that prenatal androgen concentrations influence sex-typical play behavior so that androgen exposure masculinizes and defeminizes play behaviour in humans. There was no effect of participant age or publication year, which are crude proxies of socio-cognitive or cultural influences.

References: 1. Davis JTM, Hines M. How large are gender differences in toy preferences? A systematic review and meta-analysis of toy preference research. Arch. Sex. Behav. 2020; 49: 373-394.2. Hines M. Brain gender. Oxford University Press, New York, NY. 200243. Hines M. Human gender development. Neurosci. Biobehav. Rev. 2020; 118: 89-96.