Effects of long-term erythropoietin therapy on the hypothalamopituitary-testicular axis in male CAPD patients

Objective: Gonadal dysfunction has been recognized for a long time in uremi c male patients. The present study assesses the hypothalamo-pituitary-testi cular axis and growth hormone status in male continuous ambulatory peritone al dialysis (CAPD) patients, before and after recombinant human erythropoie tin (rHuEPO) therapy. Design: Single-center prospective study. Subjects:Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were includ ed in the study. All patients were on CAPD therapy and none had received rH uEPO treatment previously. Main Outcome Measures: Blood samples were collected between 0800 and 0900 h r from all patients for the determination of basal follicle stimulating hor mone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A lut einizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 mug intravenous as a bolus injection. Blood for FSH, LH, a nd GH determinations was drawn every 30 minutes during the 3-hour test peri od. Human chorionic gonadotropin (hCG) test was performed after 48 hours. A fter estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total an d 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. Results: 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 he althy 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 sign ificantly (p<0.05). The AUCs for LH secretion before and after rHuEPO treat ment were significantly higher in patients than in controls (p<0.05). All p atients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in hea lthy subjects (p<0.001) before rHuEPO treatment. After treatment with rHuEP O, basal GH levels declined but did not normalize, and baseline levels of f ree testosterone increased significantly (p<0.05). Conclusion: Anemic uremic male patients on CAPD have normal levels of testo sterone with normal response to hCG administration, elevated basal levels o f GH, and elevated basal levels of LH, with exaggerated response to LH-RH a dministration. Improvement in anemia with rHuEPO reduced the basal levels o f 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 som e of these endocrine abnormalities.