Effects of Erythropoietin on Gonadotropin Responses to Gonadotropin-Releasing Hormone in Uremic Patients

Abstract

Long-term therapy with recombinant human erythropoietin (rhEPO) in uremic male patients undergoing hemodialysis has been followed by an increase in plasma levels of testosterone and a decrease in baseline levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely administered rhEPO on FSH and LH responses to gonadotropin-releasing hormone (GnRH) in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean ± SEM, 45.3 ± 3.9 years) with chronic renal insufficiency and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD therapy for at least 3 months, and none of them received rhEPO therapy. Patients were moderately anemic (hemoglobin 11.0 ± 0.3 g/dl) and showed 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 subject was tested with GnRH (100 μg i.v. as bolus) and with GnRH plus rhEPO (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 baseline FSH 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 FSH values reached a maximum of 25.50 ± 6.19 mU/ml in patients and of 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 value of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were significantly 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 controls (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 GnRH was injected during the rhEPO infusion, a significant (p < 0.02) reduction 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 suggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic male patients on CAPD.