Evidence for gonadal desensitization after pulsatile therapy in women with amenorrhoea?

Sixteen women with primary and secondary amenorrhoea were treated with pulsatile GnRH administered subcutaneously. Ovulation was successfully induced in 6/8 women with hypogonadotrophic hypogonadism; and in 2/2 women with idiopathic hyperprolactinaemia; but in only 3/6 women with amenorrhoea associated with an elevated LH:FSH ratio. Using serial blood sampling, we were unable to demonstrate the establishment of a physiological pattern of gonadotrophin secretion in the presence of an apparently normal menstrual cycle. Nor did we observe a consistent relationship between injection of GnRH and the resultant gonadotrophin response. A reduction or total cessation of both pituitary and gonadal sensitivity to GnRH was observed in four women. Possible reasons for these findings are discussed.