Phenotypical expression in XX males correlates with testicular response to exogenous choriogonadotropin in early infancy: does a variable degree of testicular failure determine the degree of genital ambiguity?

The 46,XX male syndrome is characterized by the presence of testicular development in subjects who lack a Y chromosome. The majority of patients have male external genitalia without ambiguity; however, 10-15% show diverse degrees of hypospadias. Testicular function is normal at birth but deteriorates thereafter. However, it has not been clarified why some cases exhibit genital ambiguity. This study examined 10 affected patients, including 4 prepubertal (< 1 year old) with hypospadias (1 glandular, 1 penile, and 2 penoscrotal). In all subjects, testicular function was evaluated by performing a stimulation with choriogonadotropin. In the postpubertal individuals, basal and poststimuli testosterone were below the reference values. Prepubertal patients had age-appropriate basal test-osterone concentrations. All responded to the choriogonadotropin challenge; however, the most significant response was observed in the patient with the glandular hypospadias, the second highest response was presented by the patient with the penile hypospadias, while both patients with the penoscrotal hypospadias had the poorest responses. These results suggest that the degree of genital ambiguity is correlated with the impairment in testosterone response to choriogonadotropin in early infancy, indicating a defect in testosterone production in XX males with genital ambiguity.