Behavioral effects of prenatal versus postnatal androgen excess in children with 21-hydroxylase-deficient congenital adrenal hyperplasia

Abstract

Systematic behavioral studies show that females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) are masculinized and defeminized in several ways; compared to their sisters, they play more with boys' toys, are more likely to use aggression when provoked, and show less interest in infants. We studied the extent to which these behavioral changes could be attributed to high levels of androgens in the prenatal vs. postnatal periods in 23 girls with CAH, aged 3-12 yr. Sex-atypical behavior was significantly associated with degree of inferred prenatal, but not postnatal, androgen excess; marked boy-typical play was associated with severe salt-wasting CAH, early age at diagnosis, and moderate genital masculinization at birth, but not with bone age advance, concurrent or cumulative high levels of 17-hydroxyprogesterone, or accelerated growth velocity in early childhood. Aggression and interest in infants were not consistently associated with indicators of prenatal or postnatal androgen excess, probably because those behaviors were measured less reliably than was toy play. The results are consistent with the idea that behavioral masculinization in girls with CAH results from high levels of androgens during fetal development and not in postnatal life.