| Gonadotropin-releasing hormone modulator | |
|---|---|
| Drug class | |
 Leuprorelin, aGnRH agonist and GnRH analogue and a prototypical GnRH modulator. | |
| Class identifiers | |
| Synonyms | GnRH receptor modulator; GnRH analogue; GnRH agonist; GnRH antagonist; GnRH blocker; LHRH modulator; LHRH receptor modulator; LHRH analogue; LHRH agonist; LHRH antagonist; LHRH blocker |
| Use | Infertility;prostate cancer;precocious puberty;breast cancer;endometriosis;uterine fibroids;transgender people |
| Biological target | GnRH receptor |
| Chemical class | Peptide;small-molecule (non-peptide) |
| Legal status | |
| In Wikidata | |
AGnRH modulator, orGnRH receptor modulator, also known as anLHRH modulator orLHRH receptor modulator, is a type ofmedication whichmodulates theGnRH receptor, thebiological target of thehypothalamic hormonegonadotropin-releasing hormone (GnRH; also known as luteinizing-releasing hormone, or LHRH).[1][2] They includeGnRH agonists andGnRH antagonists. These medications may beGnRH analogues likeleuprorelin andcetrorelix –peptides that are structurally related to GnRH – orsmall-molecules likeelagolix andrelugolix, which are structurally distinct from and unrelated to GnRH analogues.
GnRH modulators affect thesecretion of thegonadotropins,luteinizing hormone (LH) andfollicle-stimulating hormone (FSH), which in turn affects thegonads, influencing their function and hencefertility as well as theproduction ofsex steroids, including that ofestradiol andprogesterone in women and oftestosterone in men. As such, GnRH modulators can also be described asprogonadotropic orantigonadotropic, depending on whether they act to increase or decrease gonadotropins.
Shortly after the discovery of GnRH byNobel laureatesGuillemin andSchally, researchers tried to modify the GnRHdecapeptide with the intent to createanalogues that couldactivate orblock the receptor. Subsequent to the development and introduction of GnRH analogues, non-peptide or small-molecule GnRH modulators were developed and introduced.
All GnRH modulators arecontraindicated inpregnancy (pregnancy category X).
A gonadotropin-releasing hormone agonist (GnRH agonist) is a GnRH modulator that activates the GnRH receptor resulting in increased secretion of FSH and LH. Initially it was thought that GnRH agonists could be used as potent and prolonged stimulators of pituitary gonadotropin release, but it was soon recognized that GnRH agonists, after their initial stimulating action – termed a "flare" effect – eventually caused a paradoxical and sustained drop in gonadotropin secretion. This second effect was termed "downregulation" and can be observed after about 10 days. While this phase is reversible upon stopping the medication, it can be maintained when GnRH agonists use is continued for a long time. GnRH agonists can also be administered in a pulsatile manner through the use of a pump to produce a long-term stimulation of gonadotropin secretion, for instance to induce puberty.
A gonadotropin-releasing hormone antagonist (GnRH antagonist) is a GnRH modulator that blocks the GnRH receptor resulting in an immediate drop in gonadotropin (FSH, LH) secretion. GnRH antagonists are primarily used inIVF treatments to block natural ovulation.
a = Under development; not yet marketed.