Cyclosporine-Induced Alterations in the Hypothalamic Hypophyseal Gonadal Axis in Transplant Patients

Abstract

We evaluated the response of 20 male patients, 13 cadaveric kidney and 7 heart transplant recipients, to the administration of 100 micrograms GnRH (gonadotropin-releasing hormone) and 500 micrograms TRH (thyrotropic-releasing hormone). All of the heart transplant recipients and 7 of the kidney transplant patients were receiving a combination of cyclosporine, azathioprine and prednisone; while the 6 remaining kidney transplant patients received azathioprine and prednisone. The patients receiving cyclosporine had decreased plasma levels of prolactin, and manifested a blunted response to TRH administration for prolactin and TSH. The heart transplant patients had a blunted response of LH and FSH to the administration of GnRH. The levels of testosterone were found to be low in all patients regardless of the immunosuppressant therapy. Despite the low testosterone levels, no increment in the concentration of LH or FSH was present. Intramuscular administration of HCG (human chorionic gonadotropin) (Ayerst Laboratories, New York, N.Y.) failed to increase the testosterone concentration in 5 of 6 patients with renal transplants, 3 taking cyclosporine and 3 taking azathioprine. This study suggests that cyclosporine has a selective effect on the hypothalamus and/or hypophysis, resulting in lower baseline levels of plasma prolactin and a pituitary insensitivity to TRH administration. In addition, FSH and LH were low or normal in the presence of low testosterone levels, suggesting that the hypothalamic pituitary gonadal axis is impaired. Furthermore, there may be a direct toxic effect of the immunosuppressant medications on the gonads, manifested as lower testosterone levels and inability to respond to the administration of HCG.