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Metabolism of androstenedione in skin and serum levels of gonadotrophins and androgens in prepubertal boys with hypospadias.

The metabolism of 4-[1,2-3H]androstene-3,17-dione in the prepuce, axillary skin and skin from the arm was investigated in 27 boys operated for phimosis (controls) and 13 unselected boys with hypospadias (a congenital defect of the male urethra). In all types of skin investigated, androstenedione was metabolized to 5alpha-androstane-3,17-dione, 3alpha-hydroxy-5alpha-androstan-17-one, 3beta-hydroxy-5alpha-androstan-17-one and testosterone. Conversion to testosterone was found in the prepuce of two out of 11 boys with hypospadias. Mild forms of hypospadias in the age group 1--4 years had a higher level of 5alpha-reductase activity in the prepuce than controls in the same age group (P less than 0.05); no such differences were found in the few severe cases of hypospadias in this group. No other differences in 5alpha-reductase activity were found between hypospadic boys and controls. The ratio of 5alpha-reductase activity in the prepuce: 5alpha-reductase activity in skin from the arm was significantly higher (P less than 0.05) in hypospadic boys than in controls in the age group 1--4 years. Serum levels of LH and FSH were the same in normal and hypospadic boys but the concentration of prolactin in the serum was lower in boys with hypospadias compared with control subjects in the age group 1--4 years (P less than 0.005). No differences were found in serum concentrations of androstenedione, testosterone, oestradiol and testosterone-binding globulin.