A gonadotropin-releasing hormone agonist (GnRH agonist, GnRH–A) is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH.
GnRH agonists are pregnancy category X drugs.
GnRH agonists are synthetically modeled after the natural GnRH decapeptide with specific amino acid substitutions typically in position 6 and 10. These substitutions inhibit rapid degradation. Agonists with 2 substitutions include:
- leuprolide (Lupron, Eligard)
- buserelin (Suprefact, Suprecor)
- nafarelin (Synarel)
- histrelin (Supprelin LA, Vantas)
- goserelin (Zoladex)
- deslorelin (Suprelorin, Ovuplant)
Triptorelin is an agonist with only a single substitution at position 6.
Gonadotrophin-releasing hormone (GnRH) antagonists (receptor blockers) are a class of compounds that 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. In men, the reduction in LH subsequently leads to rapid suppression of testosterone release from the testes; in women it leads to suppression of estrogen release from the ovaries.
Unlike the GnRH agonists, which cause an initial stimulation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to a surge in testosterone or oestrogen levels, GnRH antagonists have an immediate onset of action, rapidly reducing sex hormone levels without an initial surge.
Currently approved GnRH antagonists include the following: