Silink M

The Children's Hospital at Westmead, Sydney, Australia


Intersex is a neonatal emergency. Gender assignment is not possible without urgent investigation in a specialized centre (chromosome analysis, imaging by ultrasound and genitogram contrast studies, hormone studies and subsequent genetic studies if indicated). Life-threatening medical conditions (various forms of congenital adrenal hyperplasia) need rapid exclusion. Decision making is helped by characterizing the chromosomal sex (46 XX, 46 XY, other), gonadal sex (testis, ovary, ovotestis, dysgenetic), internal duct sex (Wolffian, Mullerian) and external duct sex (male, female, indeterminate). Treatment needs to be individualized and may involve gender assignment, hormone replacement and reconstructive surgery. The timing and extent of surgery is a question under vigorous debate with a greater emphasis on the patient's rights to be part of the treatment recommendation.


Sexual differentiation involves many genes controlling a cascade of events affecting gonads, Mullerian and Wolffian structures, urogenital sinus, external genitalia and the CNS. Genes important in the differentiation of the indifferent gonad include WT1 and SF-1. The DSS locus is important for ovarian differentiation. Testis differentiation is dependent on SOX-9 expression. SF-1 also has a role in activating Mullerian Inhibitory Substance gene expression in the developing testis. Wolffian duct and male genital development are dependent on testosterone action (synthesis of testosterone and dihydrotestosterone, binding to androgen receptors, nuclear translocation, and subsequent gene expression). Gender identity seems to be a hormonally dependent process in the CNS.