Advanced indications for gonadotropin-releasing hormone (GnRH) analogues in gynecological oncology (Review)

Abstract

Gonadotropin-releasing hormone (GnRH) analogue has beneficial effects on the size and symptoms of endometriosis and uterine leiomyomas as a result of suppressing ovarian steroidogenesis. GnRH analogues are also the preferred treatment for advanced and even metastatic or recurred carcinomas originated from the reproductive tract. The original rationale for a GnRH analogue in the treatment was to block the endogenous gonadotropin and thereby steroid hormone secretion which was thought to stimulate tumor growth. However, more than 80% of ovarian and endometrial cancers express receptors for GnRH, and the analogues inhibit proliferation of the GnRH receptor-bearing tumor cells both in vivo and in vitro, supporting evidence for a direct antiproliferative effect. These receptors could be used for targeted chemotherapy (by tumoricidal agents linked to GnRH analogues) to improve antitumor effects and reduce side effects compared with conventional systemic chemotherapy. In addition to the anticancer action, GnRH analogues act to protect the gonads during radiation and/or chemotherapy by preferentially steering cells into cell cycle arrest with a decline in responsibility to the chemotherapy and radiation. In women who wish to maintain potential fertility, GnRH analogue therapy is successful in preventing the most critical postoperative complication, adhesion formation. The additional unrecognized benefits may add to the advantage of GnRH analogues in cancer management in gynecology.