Pulsatile luteinizing hormone releasing hormone treatment for induction of ovulation. Radioimmunoassay of plasma LHRH and comparative study of subcutaneous versus intravenous routes of administration.

To investigate the efficacy of the different routes of luteinizing hormone releasing hormone (LHRH) administration upon pituitary responsiveness, we compared plasma LHRH concentrations and pituitary LH responses in four patients with hypothalamic amenorrhea treated with pulsatile LHRH. A portable computerized infusion pump delivered sc or iv LHRH pulses of 5, 10 or 20 micrograms every 90 min. Comparison of the two modes of LHRH delivery was performed using radioimmunoassay of exogenous LHRH and studying its pharmacokinetics for a 3 pulses period. With 10 micrograms of LHRH given iv, plasma LHRH levels increased between 700 and 1000 pg/ml within 3 min and returned to basal levels in 30 min. When given sc (10 micrograms), plasma LHRH levels peaked between 80 and 100 pg/ml in 15 min and returned to basal levels 60 min later. In one patient treated with 5 micrograms per pulse iv or sc, plasma LHRH increased to 380 and 60 pg/ml respectively. In all patients, computerized analysis of LH pulses was performed during sc and iv LHRH administration. LH pulsatile release displayed a similar rhythm period with both routes. However, for the same dose of LHRH (10 micrograms), the adjusted mean of LH plasma levels was lower with the sc route. In conclusions, the pharmacokinetics of LHRH administered sc or iv displayed a similar pattern but, with equivalent doses, higher plasma LHRH levels are attained with the iv route. Concomitantly, the mean LH levels were also greater after iv administration. Ovulation can be successfully induced by both pulsatile iv and sc LHRH therapy. However, with the sc route, a higher dose of LHRH should be used to prevent a delay of ovulation or a luteal deficiency.