Related Experiment Videos
Cyclosporine-induced alterations in the hypothalamic hypophyseal gonadal axis in transplant patients
G Ramirez1, J Narvarte, P A Bittle
1Department of Internal Medicine, James A. Haley Veterans Administration Hospital, Tampa, Fla.
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.
Insights
Immunosuppressants like cyclosporine may impair the hypothalamic-pituitary axis in transplant patients, leading to low prolactin, blunted hormone responses, and low testosterone levels, potentially due to direct gonad toxicity.
Area of Science:
- Endocrinology
- Transplant Medicine
- Pharmacology
Background:
- Organ transplant recipients often receive immunosuppressive therapy.
- The endocrine effects of these medications, particularly on the hypothalamic-pituitary axis, require further investigation.
Purpose of the Study:
- To evaluate the hormonal responses to gonadotropin-releasing hormone (GnRH) and thyrotropic-releasing hormone (TRH) in male transplant patients.
- To assess the impact of immunosuppressive agents, including cyclosporine, on the hypothalamic-pituitary-gonadal axis and testosterone levels.
Main Methods:
- Administration of GnRH and TRH to 20 male kidney and heart transplant recipients.
- Measurement of plasma prolactin, TSH, LH, FSH, and testosterone levels.
- Assessment of hormonal response before and after immunosuppressive therapy and human chorionic gonadotropin (HCG) administration.
Main Results:
- Cyclosporine-treated patients showed decreased prolactin and blunted responses of prolactin and TSH to TRH.
- Heart transplant patients exhibited blunted LH and FSH responses to GnRH.
- All patients had low testosterone levels, unresponsive to HCG in most cases, suggesting potential gonad toxicity.
Conclusions:
- Cyclosporine may selectively affect the hypothalamus/hypophysis, causing reduced prolactin and pituitary insensitivity to TRH.
- Impaired hypothalamic-pituitary-gonadal axis function is indicated by low gonadotropin levels despite low testosterone.
- Immunosuppressants might have a direct toxic effect on the gonads, leading to low testosterone and HCG unresponsiveness.