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 medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmacotherapy) is an imp ...
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 ...
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 treatm ...
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 c ...
and
cetrorelix
Cetrorelix (, ), or cetrorelix acetate (, ), sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing ...
–
peptides 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 ...
s like
elagolix and
relugolix, which are structurally distinct from and unrelated to GnRH analogues.
GnRH modulators affect the
secretion 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/chorionic ...
s,
luteinizing hormone (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, and ...
(FSH), which in turn affects the
gonads, influencing their function and hence
fertility as well as the
production
Production may refer to:
Economics and business
* Production (economics)
* Production, the act of manufacturing goods
* Production, in the outline of industrial organization, the act of making products (goods and services)
* Production as a stat ...
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 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 of ...
and
progesterone 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 characteristic ...
in men. As such, GnRH modulators can also be described as
progonadotropic
A progonadotropin, or hypergonadotropin, also known as a gonad stimulant, is a type of drug which increases the secretion of one or both of the major gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This, in turn, re ...
or
antigonadotropic
An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituita ...
, depending on whether they act to increase or decrease gonadotropins.
Shortly after the discovery of GnRH by
Nobel laureates 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 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 reason to use a certain tre ...
in
pregnancy (
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 cancer ...
*
Deslorelin
Deslorelin, sold under the brand names Ovuplant, SucroMate, and Suprelorin among others, is an injectable gonadotropin releasing hormone superagonist (GnRH agonist) which is used in veterinary medicine for various indications.
Uses
Veterinary
...
*
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
*
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 c ...
*
Nafarelin
Nafarelin, sold under the brand name Synarel among others, is a gonadotropin-releasing hormone agonist (GnRH agonist) medication which is used in the treatment of endometriosis and early puberty.https://www.accessdata.fda.gov/drugsatfda_docs/label ...
*
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
In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) fr ...
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) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing ...
*
Degarelix
*
Ganirelix
Non-peptides (small-molecules)
*
Elagolix
*
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-pepti ...
a
*
Relugolix
a = Under development; not yet marketed.
See also
*
Steroidogenesis inhibitor
A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of the enzymes that are involved in the process of steroidogenesis, the biosynthesis of endogenous steroids and steroid horm ...
*
List of investigational sex-hormonal agents § GnRH/gonadotropins
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