ESPE Yearbook of Paediatric Endocrinology

sumudu@pdt.cmb.ac.lk BMC Pediatrics 2021 21:262. doi: 10.1186/s12887-021-02742-9

Brief Summary: This questionnaire-based case control study showed that girls with classical congenital adrenal hyperplasia (CAH) had more masculinized gender-role behaviour (GRB) and a tendency for ambiguous gender-identity (GI) compared to healthy children. The most likely contributor was prenatal androgen exposure.

The potential effects of CAH on gender-role behaviour (GRB) and gender identity (GI) have been reported mainly in high-income countries (HIC), with variable findings. Few studies have focused on low- and middle-income countries (LMICs). However, while the prenatal effect of CAH on the brain is expected to be similar in HICs and LMICs, the postnatal characteristics of CAH can be very different between HICs and LMICs: later diagnosis in countries without a neonatal screening for CAH, insufficient availability of hydrocortisone and fludrocortisone (implying suboptimal control of androgen secretion and more frequent central precocious puberty) and more common assignment of male gender in girls with CAH. In addition, cultural and societal norms may also differ markedly between HICs and LMICs.

This study confirms that girls with CAH in Sri Lanka report a more masculinized GRB and a higher tendency for ambiguous GI compared to controls. A limitation of the study may be that the healthy control group comprised 25 girls and 25 boys, and the authors did not mention whether the inclusion of boys as controls influenced the results. Interestingly, GI and GRB data were unaffected by postnatal factors, such as diagnosis/treatment related factors, suggesting that prenatal androgen exposure was the likely contributor to these outcomes.

The “more mature” reader will remember that, in 1984, Maguelone Forest proposed that prenatal administration of dexamethasone (which crosses the placenta) to the pregnant mother carrying a female fetus at risk of being affected by CAH could decrease virilization of the genitalia and androgenization of the brain. This approach is presently not recommended for various medical and ethical reasons (1), but a reflection on novel, safe approaches aimed at decreasing androgen secretion by the fetal adrenal in female fetuses at risk for CAH could have both physical and behavioural benefits.

Reference: 1. Dreger A, Feder EK, Tamar-Mattis A. Prenatal dexamethasone for congenital adrenal hyperplasia: an ethics canary in the modern medical mine. J Bioeth Inq. 2012; 9: 277–294. DOI: 10.1007/s11673-012-9384-9.