Mechanisms of Endocrine Dysfunction in Patients With Testicular Cancer

: To determine mechanisms of endocrine dysfunction in patients with testicular cancer, we performed static and dynamic testing of the hypothalamic-pituitary-testicular axis and testicular exocrine function in 13 patients and 11 normal control subjects, as well as in vitro studies of tumor tissue and remaining adjacent "normal" testicular tissue in the 13 patients. In tumor tissue, we demonstrated (a) elevated concentrations of total serum estradiol and serum estradiol not bound to sex hormone-binding globulin, (b) impaired spermatogenesis and sperm motility, and (c) blocking of multiple enzymes necessary for steroidogenesis. The data were consistent with a paracrine-endocrine mechanism in which tumor-produced human chorionic gonadotropin stimulates production of estradiol by "normal" testicular tissue but not tumor tissue, and the high estradiol levels then result in impaired spermatogenesis.