Gonadotrophin-releasing hormone (GnRH) antagonists are similar in structure to natural GnRH (a hormone made by neurons in the hypothalamus) but that have an antagonistic effect. GnRH antagonists are peptide molecules that are made up multiple, often synthetically produced amino acids. GnRH antagonists compete with natural GnRH for binding to GnRH receptors, thus decreasing or blocking GnRH action in the body.
GnRH antagonists competitively and reversibly bind to GnRH receptors in the pituitary gland, blocking the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. Inwomen it leads to suppression of oestrogen release from the ovaries.
Currently approved GnRH antagonists include Cetrorelix, Ganirelix, Abarelix, Degarelix.
GnRH antagonists are administered by either intramuscular injection (abarelix) or subcutaneous injection (cetrorelix, degarelix and ganirelix).
GnRH antagonists are also being investigated in the treatment of women with hormone-sensitive breast cancer and some benign disorders such as endometriosis and uterine fibroids. In endometriosis, the GnRH antagonist JV-1-36 has been shown to inhibit endometriotic cell proliferation and survival.
As with all hormonal therapies, GnRH antagonists are commonly associated with hormonal side effects such as hot flushes, headache, nausea and weight gain. When used in fertility treatment they can also be associated with abdominal pain and ovarian hyperstimulation. Subcutaneously administered agents are also associated with injection-site reactions and abarelix has been linked with immediate-onset systemic allergic reactions.