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

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

which modulates the GnRH receptor, 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

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 rele ...

(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 receptor antagonist, antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH ...

s. These medications may be GnRH analogues like leuprorelin and

cetrorelix Cetrorelix (, ), or cetrorelix acetate (, ), sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) gonadotropin-releasing hormone antagonist, antagonist. A synthetic compound, synthetic decapeptide, it is us ...

–

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s that are structurally related to GnRH – or small-molecules 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 Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer, uterine fibroids and endometriosis. ...

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

secretion 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 classical mec ...

of the gonadotropins,

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 (G ...

(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, puberty, pubertal maturat ...

(FSH), which in turn affects the

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

s, influencing their function and hence

fertility Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...

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 a ...

s, including that of

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

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 male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

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 (, ) 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 outstanding contributions in th ...

Guillemin and Schally, researchers tried to modify the GnRH

decapeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...

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 rea ...

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

(

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 * 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 ...

* Goserelin * Histrelin * Lecirelin * Leuprorelin * 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 a ...

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 Cetrorelix (, ), or cetrorelix acetate (, ), sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) gonadotropin-releasing hormone antagonist, antagonist. A synthetic compound, synthetic decapeptide, it is us ...

* Degarelix * Ganirelix

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^a *

Relugolix Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer, uterine fibroids and endometriosis. ...

^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