Effects of Long-Term Erythropoietin Therapy on the Hypothalamo–Pituitary–Testicular Axis in Male Capd Patients

Abstract

Gonadal dysfunction has been recognized for a long time in uremic male patients. The present study assesses the hypothalamo-pituitary-testicular axis and growth hormone status in male continuous ambulatory peritoneal dialysis (CAPD) patients, before and after recombinant human erythropoietin (rHuEPO) therapy. Single-center prospective study. Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were included in the study. All patients were on CAPD therapy and none had received rHuEPO treatment previously. Blood samples were collected between 0800 and 0900 hr from all patients for the determination of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A luteinizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 microg intravenous as a bolus injection. Blood for FSH, LH, and GH determinations was drawn every 30 minutes during the 3-hour test period. Human chorionic gonadotropin (hCG) test was performed after 48 hours. After estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total and free testosterone levels were measured in blood samples collected before and 48 hours after two injections of hCG. After improvement in anemia with exogenous rHuEPO, LH-RH and hCG tests were repeated. Baseline FSH concentrations before and after rHuEPO treatment were slightly higher in CAPD patients than in healthy volunteers (p = 0.85 and p = 0.70, respectively). Areas-under-the-curve (AUCs) for FSH secretion before and after rHuEPO treatment were also slightly higher in patients than in healthy volunteers (p = 1.00 and p = 0.75, respectively). The pretreatment basal LH levels in patients were significantly higher than in controls (p < 0.001). After the improvement in anemia with rHuEPO, serum LH levels declined significantly (p < 0.05). The AUCs for LH secretion before and after rHuEPO treatment were significantly higher in patients than in controls (p < 0.05). All patients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in healthy subjects (p < 0.001) before rHuEPO treatment. After treatment with rHuEPO, basal GH levels declined but did not normalize, and baseline levels of free testosterone increased significantly (p < 0.05). Anemic uremic male patients on CAPD have normal levels of testosterone with normal response to hCG administration, elevated basal levels of GH, and elevated basal levels of LH, with exaggerated response to LH-RH administration. Improvement in anemia with rHuEPO reduced the basal levels of LH and GH, but exaggerated the LH response; paradoxical GH response to LH-RH administration persisted. These results indicate a defect at the level of the hypothalamus and pituitary gland in uremic male patients undergoing CAPD, and that the improvement in anemia with rHuEPO partially restores some of these endocrine abnormalities.