Background: Disorders of sex developmebt (DSD) are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex atypical. In 46 XY DSD, the genotype is XY, but the external genitalia is incompletely virilized, ambiguous or completely female.

Design and Setting: This is a retrospective, hospital-based study, conducted at the King Saud University Medical City (KSUMC), pediatric endocrine division.

Objectives: The management of 46 XY DSD is challenging. We aimed to highlight the interplay of clinical, genetic, and cultural /religious factors, related to this, over three decades of time. Emphasizing the need to individualized approaches to management.

Materials and Methods: A retrospective review of medical records of patients, who were diagnosed with 46 XY DSD, over more than three decades were included. The diagnosis was based on recommendation.

Results: Sixty-seven patients with 46 XY DSD, aged 0-12 years were included. A wide spectrum of clinical presentation was seen with Androgen Insensivity Syndrome (AIS) was present in 20 (29.9 %), 12 (17.9 %) patients were having 5-alpha-reductase deficiency. Other testosterone biosynthesis defects were diagnosed in nine (13.4%) patients. Hypogonadotropic Hormone deficiency was the diagnosis in four (6%). Unfortunately, four of our patients, who were diagnosed with 5-alpha-reductase deficiency were wrongly assigned female sex which later re-assigned as males.

Conclusion: Management of patients with 46 XY DSD is complex, and often facing controversy. Social, cultural, and religious beliefs, often causing challenges. In suspected cases, early sex assignment should be avoided, Emphasizing the need for individualizing our approach in management of 46 XY DSD, by a trained multidisciplinary team. Parents should be involved in the decision that is based on extensive counselling.