Challenges in Sex Assignment in 46,XX Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency and 11β-hydroxylase Deficiency in Developing Countries: Insights from an Expert Center in Indonesia

Abstract

Objective: The absence of newborn screening, insufficient knowledge among medical professionals, and poor treatment adherence in congenital adrenal hyperplasia (CAH) in Indonesia causes late diagnosis. This study presents two decades of experience in gender assignment and diagnosis of 46,XX CAH.

Methods: A cohort study was carried out at a CAH referral center in Central Java, Indonesia. Data regarding clinical outcomes, molecular analysis, and sociodemographic information were taken from medical records. Participants were grouped based on current social gender, females and males. Gender at diagnosis, age at first presentation, age at first diagnosis, age at present, CAH types, virilization, puberty, birth attendant, and gender at birth decision maker significantly predict current gender identity.

Results: Among 131 individuals with 46,XX CAH, 52 (39.7%) with a sex assignment incongruent with their karyotype were included. The majority (49/52; 94.2%) had 21-hydroxylase deficiency (21OHD), while three (5.8%) had 11 beta-hydroxylase deficiency (11OHD). Individuals assigned as males at birth (3/52) had severe virilization. A change of gender occurred in 46 of 52 patients (88.46%). Midwives were the most frequent birth attendants (24/51), while pediatricians were the major decision-makers (19/51) of sex assignment.

Conclusion: In Indonesia, many 46,XX individuals with CAH were initially assigned as males due to late diagnosis, primarily caused by low awareness among healthcare professionals and exacerbated by limited medical resources and a lack of clear guidelines on sex assignment. Therefore, targeted education and standardized guidelines involving a multidisciplinary team are crucial to ensure appropriate sex assignment and care.