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.