[Transient hyperprolactinemia during ovulation induction with gonadotropin releasing hormone (GnRH) pulsatile...

Seven clomiphene-resistant normoprolactinemic anovulatory patients were treated with GnRH pulsatile administration (total 15 treatment cycles). Several problems with GnRH pulse therapy were raised through 6 unsuccessful cases. In 5 cases (10/15 treatment cycles), transient hyperprolactinemia (50-100 ng/ml) appeared immediately after the initiation of the treatment and persisted for 6-10 days. Follicle maturation and ovulation was not induced in these cases. Frequent blood sampling failed to demonstrate GnRH-induced LH secretion in 3 cases. Synchronous secretion of PRL with LH was observed when serum PRL levels were low, but not in situations with elevated serum PRL levels. The lack of GnRH-induced LH secretion indicates the down-regulation of the pituitary with increased frequency of GnRH pulses due to intrinsic and exogenous GnRH. The synchrony of LH and PRL suggests the contribution of GnRH-mediated PRL releasing factor (PRF) through a paracrine system between gonadotrophs and lactotrophs. Transient hyperprolactinemia observed in the current study might be attributable to a relative increase in GnRH to a GnRH-associated peptide (GAP), a constituent of GnRH prohormone and possessing an intrinsic effect of PRL suppression, by exogenously administered GnRH, causing overwhelming superiority of GnRH-mediated PRF. Transient hyperprolactinemia and regulation of the pituitary may hamper ovulation induction with GnRH pulse therapy when applied to cases with intact hypothalamic-pituitary axis.