Leydig cell responsiveness with germinal cell resistance to gonadotropin therapy in Kallman's syndrome

Abstract

Patient's with Kallman's syndrome have been divided into gonadotropin-sensitive gonadotropin-resistant types. This has been based on the testosterone response of the Leydig cells to human chorionic gonadotropin (HCG) and the resultant sexual characteristics. Whether the germinal epithelium is similarly sensitive has not been previously assessed. The present study was set up to see if a male with anosmia and hypogonadotropic hypogonadism could be made fertile by treating with human menopausal gonadotropins (HMG) in combination with HCG, a regime previously found effective in other types of hypogonadotropic hypogonadism. The patient was previously shown to be HCG-responsive by the induction of secondary sexual characteristics following gonadotropin therapy. This was confirmed by measuring serum testosterone levels before and after the administration of HCG. Therapy with HMG, 75 IU intramuscularly, and HCG, 2,000 intramuscularly three times a week, was started. After six months, despite perfectly normal secondary sexual characteristics and near normal-sized testes, he still showed azoospermia. His HMG was increased to 150 intravenously thrice weekly. After an additional two months of therapy, his count was still zero. A testicular biopsy was performed and disclosed Leydig cell hyperplasia but very little active spermatogenesis. Although this man was gonadotropin-sensitive as far as his Leydig cells are concerned, his germinal epithelium was resistant. Thus, HCG sensitivity does not ensure fertility.