Peer-reviewed article

SUN-071 Prenatal and Post-Natal Influence of Androgens in the Psychosexual Development in Individuals with 21-hydroxylase Congenital Adrenal Hyperplasia

Batista R, Inacio M, de Miranda M, Gomes P, Cabral H et al. · 8 May 2020

Abstract

Abstract Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up of 90% of CAH. It is caused by several mutations in the CYP21A2 gene. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess, either with salt-wasting or simple virilizing forms. Androgens play a crucial role in the human psychosexual development favoring male psychosexuality. This study was designed to evaluate the impact of androgens on psychosexuality of a cohort of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort is made up of 94 four individuals with proved molecular defect of the CYP21A2 gene. External genitalia virilization was scored using Prader scale. Clinical phenotype, age at diagnosis, sex assignment, gender reassignment and gender change were all assessed. The gender role at childhood was assessed through the playmates and favorite toys at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report and sexual attractiveness. Compliance of glucocorticoid replacement was assessed by serum testosterone and 17OHP levels. Results: CAH was diagnosed at neonatal time in 67% (61 out 94). 51% (n=48) had the salt-wasting form (SW) and 49% (n=46) had the simple virilizing form (SV). While all cases of SW were diagnosed at neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (F 38.9; p=<.001). A total of 84.5% were assigned as female at birth. The median of Prader score was 3 in both phenotypes. Male sex assignment was associated with more virilized external genitalia (Prader 4 and 5) while the opposite (Prader 1 and 2) was associated with female sex assignment (X2 16, p=.002, V=0.44). Gender change from female to male occurred in 7 cases (7.4%). All cases of gender change had SV form (p=.006). The mean age at diagnosis of those who changed gender was 7.92 yr and 2.67 yr for those who kept the assigned gender, p=.04). There was a strong association between male toys at childhood and male gender identity at adulthood (X2 28, p=.0001, V=0.59). A total of 11% defined themselves as homosexual. External genitalia virilization was associated with gynophilic sexual attractiveness (X2 82, p=0.001, V=0.59). Compliance issues were identified in 60% of individuals who changed their gender. Inappropriate hormonal control between 2 and 11 years of age was also associated with gender change (p=.04). Conclusion: Prenatal androgen exposure favors male psychosexuality in CAH. This influence is substantiated by post-natal androgen exposure since gender changed from female to male occurred in individuals with late diagnosis and bad compliance.