The role of LHRH agonists and antagonists

Administration of GnRH analogues (agonists as well as antagonists) produces suppression of the pituitary---gonadal axis, thus inhibiting the secretion of LH, FSH and sexual steroids. For this reason, analogs are indicated in all those clinical situations where suppression of gonadotrophins (precocious puberty, contraception) or of sexual steroids (endometriosis, prostate hyperplasia, cancer, uterine fibroids) is desired. For several years GnRH agonists have been used in combination with gonadotrophins for ovarian stimulation for assisted reproduction in order to control premature LH surges and to reduce cancellation rate with improvement of the pregnancy rate per cycle. This effect is obtained after 2 weeks of agonist administration. The immediate suppression of the pituitary achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. The prevention of a premature LH surge by GnRH antagonists can be obtained by multiple dose or by a single administration. Both protocols offer the following advantages over the agonists: they require fewer ampoules of gonadotrophins, shorter duration of stimulation, there is a preserved pituitary response to GnRH, less risk of ovarian hyperstimulation syndrome and the luteal phase seems to be more preserved. The main disadvantages of the antagonists are that they are expensive and that pregnancy rate appears to be slightly lower than with the agonists. GnRH antagonists will probably replace agonists in ovarian stimulation treatment for assisted reproduction techniques.