Behavioral and physical masculinization are related to genotype in girls with congenital adrenal hyperplasia.
Girls with congenital adrenal hyperplasia (CAH) exhibit behavioral masculinization. There is controversy about the roles of pre- and postnatal androgens, social factors, and chronic illness in its etiology. To assess the effect of chronic illness, we compared behavioral masculinity in 24 CAH girls and 25 diabetic girls aged 3-12 yr from Manchester using two sensitive questionnaires, and an overall masculinity score M (high = masculine) was derived. To assess the contributions of pre- and postnatal androgens, the CAH subjects were categorized into genotype groups (G) according to the reported severity of loss of CYP21 function: G1 (n = 10, null mutations), G2 (n = 9, intron 2G), G3 (n = 3, I172N), and G4 (n = 2, unknown loss of function). In CAH girls, relationships between G, Prader degree of genital masculinization at birth, bone age advance, and M were assessed. CAH girls were less feminine and more masculine than diabetic girls (P < 0.001), who were not significantly different from U.S. controls. Among the CAH girls, those in G1 and 2 were more genitally masculinized than those in G3 and 4 (P < 0.009) and had higher M (P < 0.025). M was negatively correlated with advanced bone age (r = -0.5; P = 0.02). CAH girls, but not diabetic girls, demonstrated behavioral masculinization. Both physical and behavioral masculinization were related to each other and to genotype, indicating that behavioral masculinization is a consequence of prenatal androgen exposure.
Hall
Catherine M
CM
Royal Manchester Children's Hospital, Manchester M27 4HA, United Kingdom. catherine.hall@cmmc.nhs.uk
Jones
Julie A
JA
Meyer-Bahlburg
Heino F L
HF
Dolezal
Curtis
C
Coleman
Michelle
M
Foster
Peter
P
Price
David A
DA
Clayton
Peter E
PE
D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D000728:Androgens / Q000502:physiology; D001519:Behavior; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage; D005836:Genitalia, Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D009154:Mutation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000502:physiology; D011795:Surveys and Questionnaires; D014770:Virilism / Q000235:genetics*
D000728:Androgens; D013255:Steroid 21-Hydroxylase; D005438:Fludrocortisone; D006854:Hydrocortisone