Gonadotropin-releasing hormone and reproductive medicine

The hypothalamic gonadotropin-releasing hormone (GnRH) is a key regulator of the reproductive system, mainly through its effects on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. Gonadotropin-releasing hormone analogues are modifications of the natural decapeptide, being either agonists (GnRHa) or antagonists. GnRHa may imitate the native hormone and induce an endogenous LH surge; however, sustained treatment with GnRHa results in complete refractoriness of LH and FSH production. This aspect of GnRHa action is the main application of the GnRHa in reproduction today. The hypogonadotropic hypogonadal state that results from the sustained treatment is the basis for additional applications of the GnRHa. The agonists appear to be effective, to some extent, for the treatment of endometriosis and were proved to be beneficial prior to surgery for fibroma uteri. GnRHa is used in assisted reproduction for both induction of an endogenous LH surge and for induction of ovulation, and its capacity to cause refractoriness of the pituitary may be used to avoid a premature LH surge. It is suggested that the GnRHa have a direct effect on ovarian steroidogenesis, which is independent of its action on the pituitary. This unwanted effect and other possible drawbacks of the agonists are thought to be eliminated with the use of the antagonists. The mechanism of action of these antagonists is through competitive blocking of the GnRH receptor, which results in a rapid but reversible suppression of gonadotropin secretion. As for GnRHa, GnRH antagonists have been proven effective to prevent the LH surge and to reduce the incidence of severe ovarian hyperstimulation syndrome in controlled ovarian stimulation cycles.