The frequency of androgen receptor deficiency in infertile men

To ascertain the frequency of androgen resistance as the cause of male infertility and to determine whether endocrine abnormalities are a universal feature of the disorder, we measured the androgen receptor in fibroblasts cultured from the genital skin of 28 unrelated phenotypically normal men with idiopathic azoospermia or oligospermia. The amounts of androgen receptor were compared with those in genital skin fibroblasts from a variety of other subjects, including 10 men with azoospermia of known cause, 5 normal men, 28 subjects with disorders of androgen formation of metabolism of known cause, and 28 persons with documented disorders of the androgen receptor (testicular feminization and Reifenstein syndrome). The mean androgen receptor Bmax (amount of high affinity binding) was 12 fmol/mg protein or greater in 10 infertile men with azoospermia of known cause and in 6 infertile men with mild oligospermia. In fibroblasts from 1 to 4 individuals with severe oligospermia of unknown cause (less than 1 million/ml) and 8 of 18 subjects with idiopathic azoospermia, the androgen receptor Bmax was less than 12 fmol/mg protein. The mean value in these 9 men was not significantly different from that in subjects with testicular feminization or Reifenstein syndrome. Serum concentrations of testosterone and LH were normal in 6 of these 9 infertile men, and plasma production rates of testosterone were elevated in only 2 of the 6 men studied in whom the Bmax values in genital skin fibroblasts were less than 12 fmol/mg protein. We conclude that androgen resistance may be the cause of a significant fraction (40% or more) or idiopathic male infertility due to azoospermia or severe oligospermia, and that this disorder may not be manifested by a functional defect in the pituitary-testicular axis.