PITUITARY-RESPONSIVENESS AFTER ADMINISTRATION OF A GNRH AGONIST DEPOTFORMULATION - DECAPEPTYL-CR

OBJECTIVE This study was focused on the pattern of LH release from the pituitary during the initial response to high dose GnRH agonist admin istration. Secondly, the pattern of LH release and the pituitary respo nsiveness to physiological and pharmacological stimulation during long -term pituitary suppression by a high dose GnRH agonist was studied. I n addition, the relation between serum agonist levels and pituitary fu nction and responsiveness was investigated. DESIGN DTrp6GnRH in microc apsules (Decapeptyl CR) was administered i.m. to 12 women on the third day of the cycle. High-rate blood sampling was carried out during the first 48 hours after the injection. Secondly, high-rate blood samplin g for 6 hours and a GnRH challenge were performed before and weekly af ter administration, from week 4 till week 9. All samples were assayed for LH and FSH. LH patterns were analysed by applying a computerized p ulse detection program. In the second or third week an oestradiol benz oate test was performed. Finally, triptorelin levels were measured bef ore and weekly after administration. PATIENTS Twelve patients, sufferi ng from tubal infertility and recruited from the waiting list for in-v itro fertilization/embryo transfer (IVF/ET) participated in the study. RESULTS During the first 48-hour period, LH and FSH levels demonstrat ed a rapid rise to peak values after 4 hours, subsequently declining t o nearly normal levels. E2 rose to peak values at 12 hours and returne d to the follicular range thereafter. LH pulse patterns showed a rapid increase in pulse intervals leading to a near absence of LH pulses at the end of the 48-hour period. From the fourth till the seventh week after agonist administration, LH pulse patterns showed a markedly incr eased pulse interval, decreased pulse amplitude, and a severely decrea sed mean LH level. In the same period, LH responses to GnRH were sever ely blunted or absent. Restoration of the pre-injection LH pulse patte rn and the LH response to GnRH was observed during the eighth and nint h week. Oestradiol benzoate challenges showed an E2 rise to preovulato ry levels in response to the injections. However, no changes were obse rved in LH and FSH concentrations. Triptorelin levels showed a peak wi thin 48 hours and gradual decline towards pretreatment values in week eight. CONCLUSIONS It is concluded from the study, that after administ ration of triptorelin depot in the early follicular phase, desensitiza tion of the pituitary starts to develop within 24 hours. Pituitary res ponsiveness is completely absent in the second week and continues to e xist until the eighth week after injection, when the agonist has disap peared from the circulation. These findings suggest profound alteratio ns in GnRH receptor availability and post-receptor pathways, that prev ent the pituitary from responding to physiological stimuli.