Androgen Insensitivity as a Cause of Infertility in Otherwise Normal Men

To ascertain if androgen insensitivity causes severe oligospermia or azoospermia we studied three unrelated, phenotypically normal men with long histories of infertility. The mean plasma concentrations and production rates of testosterone were 14.3 ng per milliliter and 10.1 mg per day, respectively, values approximately twice the average found in normal men. Serum luteinizing hormone concentrations were elevated in two of the three subjects. The specific high-affinity dihydrotestosterone binding capacity of cultured genital-skin fibroblasts was 8, 0 and 10 fmol per milligram of cellular protein, values half (or less) of those from normal men and women but similar to values in subjects with partial androgen insensitivity manifested by incomplete testicular feminization or Reifenstein syndrome. The low amount of androgen receptor and the combination of high serum gonadotropins and plasma testosterone production rates suggest that the defective spermatogenesis in these infertile men was the consequence of androgen insensitivity. (N Engl J Med 300:223–227, 1979) SEVERAL hereditary disorders that result in resistance to androgen action have been characterized in detail.^{1 2 3 4 5 6 7} In the syndromes of complete testicular feminization^{1 2 3} and incomplete testicular feminization⁴ and in the Reifenstein syndrome,^{5 6 7} there is a deficiency of the cytosolic receptor protein responsible for the transport of dihydrotestosterone into the nucleus.^{8 9 10 11} In all three of these syndromes, persons affected manifest variable abnormalities of phenotypic differentiation. The nature of the factor (or factors) governing the variable phenotypic expression in these disorders despite similar levels of androgen receptor is unknown. We now report data obtained in three unrelated, normal phenotypic men that expand the.