GnRH-antagonists in reproductive medicine

Suppression of sex steroid production based on desensitisation and down-regulation of pituitary gonadotropin-releasing hormone (GnRH)-receptors by agonistic GnRH-analogues resulting in the blockage of gonadotropin release from the anterior pituitary gland is a well-established approach in a variety of clinical conditions. Antagonistic analogues of GnRH exert their effect by competing with endogenous GnRH for pituitary binding sites. Because of the lack of any intrinsic activity of these compounds, the characteristic initial ‘flare-up’ effect of GnRH-agonist administration is absent. A more rapid suppression of gonadotropin release from the pituitary gland can be achieved, enabling shorter treatment regimes in ovarian hyperstimulation for assisted reproduction. As yet, GnRH-antagonists have attained market approval only for the indication of premature luteinizing hormone (LH) surge prevention in controlled ovarian hyperstimulation and palliative treatment of advanced prostatic cancer. However, GnRH-antagonists may be useful in a variety of other malignant and non-malignant indications where rapid sex steroid suppression is desired, such as uterine leiomyomas, endometriosis, gynaecological cancers or benign prostatic hyperplasia. In the context of infertility treatment, available data on the application of GnRH-antagonists in the treatment of endometriosis and uterine leiomyomas are reviewed.