Enduring prenatal androgen effects on the female brain

Structural sex differences in the brain have been reported as early as infancy. Prenatal androgens have been hypothesized to contribute to these sex differences but the available evidence is inconclusive. Congenital adrenal hyperplasia (CAH) is a genetic variant that causes high levels of androgens during gestation in females and more male-typical behaviour after birth, whereas androgen levels and behaviour in males with CAH are largely typical. To assess whether prenatal androgens affect brain anatomy, we studied the largest CAH sample to date, matched pair-wise to a control group for sex, age, education and verbal intelligence. Anatomical sex differences were quantified using T1-weighted brain scans and a relevance-vector machine, which generated a continuous probabilistic brain sex index. Females with CAH exhibited significantly more male-like brain characteristics than control females, whereas no differences were observed between males with CAH and control males. This observed shift towards a male-typical brain anatomy in females with CAH supports the hypothesis that prenatal androgen exposure has formative effects on the human brain that persist into adulthood.