Frequency-varied versus unvaried pulsatile LH-RH substitution in hypothalamic amenorrhea

In 26 patients with hypothalamic amenorrhea cyclic ovarian function was reestablished by pulsatile LH-RH substitution. Two LH-RH regimens were tested. In group A (n = 13) LH-RH pulses (12 micrograms i.v.) were administered by means of a portable mini-pump (Auto-Syringe) at the unvaried frequency of one pulse every 96 min throughout the follicular phase. In group B (n = 13) LH-RH pulse intervals of 4 h (for 2 consecutive days), 3 h (for 1 day) and 96 min (for the rest of the follicular phase) were selected for initiation of follicle growth. After ovulation pump-assisted pulsatile LH-RH substitution was either maintained at the 96-min rhythm or replaced by LH-RH nasal-spray (200 micrograms/sniff) applied once every 4 h until the onset of menstruation or detection of pregnancy. While in group A patients changes in the pattern of luteal LH-RH support (pump-assisted versus nasal-spray assisted) resulted in rapid luteolysis, such effects did not occur in group B patients. It is suggested that LH-RH pulse frequency at the initial stage of follicular development is of importance for the quality of follicular development and thus luteal function. Both LH-RH regimens resulted in pregnancies (six times singletons and once twins). In the meantime, all children have been born and are healthy.