Gonadotropin-releasing-hormone-receptor antagonists.
Pulsatile gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH) and thus controls the hormonal and reproductive function of the gonads. Blockade of GnRH effects may be wanted for a variety of reasons-eg, to prevent untimely luteinisation during assisted reproduction or in the treatment of sex-hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. Only recently have GnRH-receptor antagonists, that immediately block GnRH's effects, been developed for clinical use with acceptable pharmacokinetic, safety, and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All current indications for GnRH-agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence so far has been in assisted reproduction and prostate cancer.
Huirne
J A
JA
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Centre, PO Box 7057, 1007MB, Amsterdam, Netherlands.
Lambalk
C B
CB
D000328:Adult; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone