A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field an ...

which modulates the

GnRH receptor The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin ...

, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of the

hypothalamic hormone The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...

gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...

(GnRH; also known as luteinizing-releasing hormone, or LHRH). They include

GnRH agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...

s and

GnRH antagonist Gonadotropin-releasing hormone antagonists (GnRH antagonists) are a class of medications that antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH). They are used in ...

s. These medications may be GnRH analogues like

leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical castr ...

and cetrorelix –

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

s that are structurally related to GnRH – or

small-molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...

s like

elagolix Elagolix, sold under the brand name Orilissa, is a gonadotropin-releasing hormone antagonist (GnRH antagonist) medication which is used in the treatment of pain associated with endometriosis in women. It is also under development for the treatme ...

and relugolix, which are structurally distinct from and unrelated to GnRH analogues. GnRH modulators affect the

secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...

of the

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chori ...

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (Gn ...

(LH) and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, ...

(FSH), which in turn affects the

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces ...

s, influencing their function and hence

fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Ferti ...

as well as the production of

sex steroid Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects ar ...

s, including that of

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

and

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

in women and of

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteris ...

in men. As such, GnRH modulators can also be described as progonadotropic or antigonadotropic, depending on whether they act to increase or decrease gonadotropins. Shortly after the discovery of GnRH by

Nobel laureates The Nobel Prizes ( sv, Nobelpriset, no, Nobelprisen) are awarded annually by the Royal Swedish Academy of Sciences, the Swedish Academy, the Karolinska Institutet, and the Norwegian Nobel Committee to individuals and organizations who make ...

Guillemin and Schally, researchers tried to modify the GnRH decapeptide with the intent to create analogues that could activate or

block Block or blocked may refer to: Arts, entertainment and media Broadcasting * Block programming, the result of a programming strategy in broadcasting * W242BX, a radio station licensed to Greenville, South Carolina, United States known as ''96.3 ...

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 are

contraindicated In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reas ...

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

(

pregnancy category The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...

X).

GnRH agonists

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.

Peptides (analogues)

Buserelin Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis. It is also used for other indications such as the treatment of premenopausal breast canc ...

* Deslorelin * Fertirelin *

Gonadorelin Gonadorelin is a gonadotropin-releasing hormone agonist (GnRH agonist) which is used in fertility medicine and to treat amenorrhea and hypogonadism. It is also used in veterinary medicine. The medication is a form of the endogenous GnRH and is i ...

Goserelin Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer. It is an injectable gon ...

Histrelin Histrelin acetate, sold under the brand names Vantas and Supprelin LA among others, is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency.

* Lecirelin *

Leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical castr ...

* Nafarelin * Peforelin *

Triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is ...

GnRH antagonists

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 in IVF treatments to block natural ovulation.

Peptides (analogues)

* Abarelix * Cetrorelix *

Degarelix Degarelix, sold under the brand name Firmagon among others, is a hormonal therapy used in the treatment of prostate cancer. Testosterone is a male hormone that promotes growth of many prostate tumours and therefore reducing circulating testoster ...

Ganirelix Ganirelix acetate (or diacetate), sold under the brand names Orgalutran and Antagon among others, is an injectable competitive gonadotropin-releasing hormone antagonist (GnRH antagonist). It is primarily used in assisted reproduction to control o ...

Non-peptides (small-molecules)

Elagolix Elagolix, sold under the brand name Orilissa, is a gonadotropin-releasing hormone antagonist (GnRH antagonist) medication which is used in the treatment of pain associated with endometriosis in women. It is also under development for the treatme ...

Linzagolix Linzagolix, sold under the brand name Yselty, is a medication used in the treatment of uterine fibroids.https://www.ema.europa.eu/en/documents/product-information/yselty-epar-product-information_en.pdf Linzagolix is a small-molecule, non-pept ...

^a * Relugolix ^a = Under development; not yet marketed.

References

External links

History of GnRH agonist and antagonist development
{{Use dmy dates, date=December 2020 Antigonadotropins Fertility medicine Gonadotropin-releasing hormone and gonadotropins Hormonal antineoplastic drugs Progonadotropins

GnRH agonists

Peptides (analogues)

GnRH antagonists

Peptides (analogues)

Non-peptides (small-molecules)

See also

References

External links