Behavioral and Physical Masculinization Are Related to Genotype in Girls with Congenital Adrenal Hyperplasia

• Published in: The journal of clinical endocrinology and metabolism 2004-01, Vol.89 (1), p.419-424
• Main Authors: Hall, Catherine M., Jones, Julie A., Meyer-Bahlburg, Heino F. L., Dolezal, Curtis, Coleman, Michelle, Foster, Peter, Price, David A., Clayton, Peter E.
• Format: Article
• Language: English
• Subjects: Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - genetics; Adrenal Hyperplasia, Congenital - physiopathology; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Androgens - physiology; Behavior; Biological and medical sciences; Child; Child, Preschool; Diabetes Mellitus; Endocrinopathies; Female; Fludrocortisone - administration & dosage; Fundamental and applied biological sciences. Psychology; Genitalia, Female; Genotype; Hormone Replacement Therapy; Humans; Hydrocortisone - administration & dosage; Medical sciences; Mutation; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pregnancy; Prenatal Exposure Delayed Effects; Steroid 21-Hydroxylase - genetics; Steroid 21-Hydroxylase - physiology; Surveys and Questionnaires; Vertebrates: endocrinology; Virilism - genetics
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030696

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.