Male sex assignment in severely virilized 46,XX children with congenital adrenal hyperplasia

Introduction Increased androgen production in 46,XX individuals with congenital adrenal hyperplasia leads to a variable degree of external genital virilization, often complicating the decision regarding sex assignment after birth. Methods In this single tertiary center retrospective study, we analyzed individuals with 46,XX karyotype and 21-hydroxylase deficiency with Prader score V or EMS 8-9, who were assigned and reared as male in the last 40 years. In parallel, we conducted a comprehensive review of published case reports on 46,XX male CAH patients to gain insight into their gender identity outcomes, surgical interventions, and quality of life. Results We identified four severely virilized 46,XX CAH patients, who were assigned and reared as male and have maintained a stable male gender identity. In addition, we found 63 similar published cases in the literature between 1963 and 2025. Outcome data were available in 50 cases. Among them, 43/50 patients were satisfied with male gender identity, although 3/43 underwent male to female and back to male reassignment. Conclusion Our experience with four patients aligns with several published case reports showing that 46,XX CAH infants with severe genital virilization reared as male may develop and maintain a stable male gender identity throughout life. However, if male sex assignment is chosen for a 46,XX child, parents should be counseled about fertility implications, future surgical needs, potential height-related concerns and the possibility of testosterone treatment. Nevertheless, individualized care, shared decision-making, parental involvement and family support appear to be essential for a positive outcome.