EFFECTS OF ERYTHROPOIETIN ON GONADOTROPIN RESPONSES TO GONADOTROPIN-RELEASING-HORMONE IN UREMIC PATIENTS

Long-term therapy with recombinant human erythropoietin (rhEPO) in ure mic male patients undergoing hemodialysis has been followed by an incr ease in plasma levels of testosterone and a decrease in baseline level s of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely admin istered rhEPO on FSK and LH responses to gonadotropin-releasing hormon e (GnRH) in a group of uremic patients undergoing continuous ambulator y peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean +/- SEM, 45.3 +/- 3.9 years) with chronic renal insufficien cy and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD ther apy for at least 3 months, and none of them received rhEPO therapy. Pa tients were moderately anemic (hemoglobin 11.0 +/- 0.3 g/dl) and showe d testosterone levels significantly lower than those found in control subjects (3.47 +/- 0.37 vs. 6.91 +/- 0.49 ng/ml, p < 0.001). Each subj ect was tested with GnRH (100 mu g i.v. as bolus) and with GnRH plus r hEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before GnRH injection) on different days. Blood samples for FSH and LH were obtained between -30 and 120 min. In uremic patients the baselin e FSK levels were higher than those found in control subjects (18.88 /- 5.41 vs. 6.41 +/- 1.10 mU/ml, p < 0.05). After GnRH administration FSK values reached a maximum of 25.50 +/- 6.19 mU/ml in patients and o f 12.50 +/- 2.02 mU/ml in controls (p < 0.05). rhEPO infusion produced a significant (p < 0.01) decrease in the area above the baseline Valu e of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were si gnificantly higher in patients than in controls (15.56 +/- 3.41 vs. 2. 58 +/- 0.36 mU/ml, p < 0.001). LH peak and area under the curve of LH secretion after GnRH were significantly higher in patients than in con trols (45.25 +/- 6.28 vs. 26.83 +/- 4.62 mU/ml, p < 0.05, and 77.02 +/ - 11.30 vs. 34.40 +/- 5.22 mU.h/ml, p < 0.005, respectively). When GnR H was injected during the rhEPO infusion, a significant (p < 0.02) red uction in LH concentrations at 60, 90, and 120 min was found in uremic patients. Accordingly, the LH area under the curve was significantly reduced in patients (65.99 +/- 11.44 mU.h/ml, p < 0.05). rhEPO had no effect on GnRH-induced LH release in control subjects. These results s uggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic male patients on CAPD.