Gonadotropin-releasing hormone antagonists: pharmacology and clinical use in women

Gonadotropin-releasing hormone (GnRH) antagonists are now widely used in protocols of patients with controlled ovarian hyperstimulation to treat infertility. By competitively binding to the pituitary GnRH receptor, they lead to a rapid suppression of gonadotropins and consecutively sex hormones. In the past, GnRH agonists have been exclusively used for these patients, with the disadvantage of an initial rise of gonadotropins--the flare-up effect. Several trials comparing the agonistic and antagonistic analogs of GnRH found no significant differences in oocyte quality, fertilization and pregnancy rates. Slightly lower implantation and pregnancy rates, and estradiol levels, in patients treated with GnRH antagonists has raised concern about eventual extrapituitary adverse effects. However, no convincing evidence has yet been found for any detrimental ovarian effects of GnRH antagonists. The lower rate of ovarian hyperstimulation syndrome, a potentially severe disadvantage of infertility treatment, is a positive feature of GnRH antagonists. The key point is that GnRH antagonists have been proven to be as effective and safe as GnRH agonists. This broadens the spectrum of indications for GnRH antagonists to sex hormone-dependent disorders like endometriosis, uterine fibroids, and gynecological cancers such as breast and ovarian cancer.