GONADOTROPHIN RESPONSES TO GnRH PULSES IN HYPOGONADOTROPHIC HYPOGONADISM: LH RESPONSIVENESS IS MAINTAINED IN THE PRESENCE OF LUTEAL PHASE CONCENTRATIONS OF OESTROGEN AND PROGESTERONE

Abstract

LH pulse secretion changes during the menstrual cycle from a rapid regular pattern in the follicular phase to a slower and irregular pattern in the luteal phase. To determine whether the irregular LH pulse pattern in the luteal phase reflects altered GnRH secretion or altered pituitary responsiveness to GnRH, we gave low dose GnRH pulses (25 ng/kg i.v.) every 2 h or every hour for 10 or 12 d to three women with isolated GnRH deficiency. After 4 d of GnRH alone, oestradiol (E 2 ) was given and after 6 d progesterone (P) was added to mimic the hormonal milieu of the luteal phase. LH and FSH were measured every 4 h throughout and also every 20 min for 6 or 12 h, before and after GnRH alone (day 0 and day 4), after E 2 (day 6), and after E 2 + P (day 10 and day 12). Both GnRH pulse frequencies resulted in a rapid increase in plasma FSH to peaks on day 4 (every 2 h) and day 2 and 3 (every hour). FSH concentrations then declined as plasma E 2 rose to 50–80 pg/ml reflecting the selective inhibitory effect of E 2 on FSH release. Plasma LH was also increased after the hourly GnRH injections and this regimen was associated with a more rapid rise in E 2 reflecting follicular maturation. In contrast to the differences in mean hormone concentrations, administration of GnRH at both frequencies resulted in sustained one-on-one responsiveness of LH that was maintained in the presence of both oestrogen and progesterone at mid-luteal phase concentrations. We conclude that the slow frequency of LH pulses observed during the luteal phase reflects decreased GnRH pulse frequency rather than impaired pituitary responsiveness to GnRH.