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.
Contents
- 1 Medical uses
- 2 Side effects
- 3 Flare effect and downregulation
- 4 Agonists with double and single substitutions
- 5 Administration
- 6 See also
- 7 External links
- 8 References
Medical uses
GnRH agonists are useful in:
- Suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, which is an essential component in in vitro fertilisation (IVF). Typically, after GnRH agonists have induced a state of hypoestrogenism, exogenous FSH is given to stimulate ovarian follicle, followed by human chorionic gonadotropins (hCG) to trigger oocyte release. GnRH agonists routinely used for this purpose are: buserelin, leuprorelin, nafarelin, and triptorelin.[1]
- Final maturation induction after having performed controlled ovarian hyperstimulation. Usage of GnRH agonist for this purpose necessitates using a GnRH antagonist instead of a GnRH agonist for suppression of spontaneous ovulation, because using GnRH agonist for that purpose as well inactivates the axis for which it is intended to work for final maturation induction.
- Treatment of cancers that are hormonally sensitive and where a hypogonadal state decreases the chances of a recurrence. Thus they are commonly employed in the medical management of prostate cancer and have been used in patients with breast cancer.
- Treatment of delaying puberty in individuals with precocious puberty.
- Delaying puberty pending treatment decisions in children with gender dysphoria
- Management of female disorders that are dependent on estrogen productions. Women with menorrhagia, endometriosis, adenomyosis, or uterine fibroids may receive GnRH agonists to suppress ovarian activity and induce a hypoestrogenic state.
- Suppressing hormone levels in transsexual people, especially trans women.
- Severe cases of congenital adrenal hyperplasia
- Temporary Suppression of Fertility in Female Dogs
- Induction of Ovulation in Mares
Women of reproductive age who undergo cytotoxic chemotherapy have been pretreated with GnRH agonists to reduce the risk of oocyte loss during such therapy and preserve ovarian function. Further studies are necessary to prove that this approach is useful.
Side effects
Side effects of the GnRH agonists are signs and symptoms of hypoestrogenism, including hot flushes, headaches, and osteoporosis. In patients under long-term therapy, small amounts of estrogens could be given back (“add-back regimen”) to combat such side effects and to prevent bone wastage. Generally, long-term patients, both male and female, tend to undergo annual DEXA scans to appraise bone density.
There is also a report that GnRH agonists used in the treatment of advanced prostate cancer may increase the risk of heart problems by 30%.[2]
Flare effect and downregulation
Agonists do not quickly dissociate from the GnRH receptor. As a result initially there is an increase in FSH and LH secretion (so-called "flare effect").
However after about ten days, a profound hypogonadal effect (i.e. decrease in FSH and LH) is achieved through receptor downregulation by internalization of receptors. Generally this induced and reversible hypogonadism is the therapeutic goal.
Agonists with double and single substitutions
GnRH agonists are synthetically modeled after the natural GnRH decapeptide with specific modifications, typically in position 6 (amino acid substitution), 9 (alkylation) and 10 (deletion). These substitutions inhibit rapid degradation. Agonists with two substitutions include: leuprolide (Lupron, Eligard), buserelin (Suprefact, Suprecor), histrelin (Supprelin LA, Vantas), goserelin (Zoladex), and deslorelin (Suprelorin, Ovuplant). The agents nafarelin (Synarel) and triptorelin are agonists with single substitutions at position 6.
Administration
These medications can be administered intranasally, by injection, or by implant. Injectables have been formulated for daily, monthly, and quarterly use; and implants can last from 1 to 12 months.
See also
- Gonadotropin-releasing hormone antagonist
External links
- Buserelin website
- Use of agonists in endometriosis
- Lupron, by manufacturer
- Lupron victims hub, website against use of this drug.
- 10th International Symposium on GnRH
- SupprelinLA, by Endo Pharmaceuticals, Inc.
- Information of use of Zoladex in prostate cancer
References
- ^ van Loenen AC, Huirne JA, Schats R, Hompes PG, Lambalk CB (November 2002). "GnRH agonists, antagonists, and assisted conception". Semin. Reprod. Med. 20 (4): 349–64. doi:10.1055/s-2002-36713. PMID 12536358.
- ^ http://www.genengnews.com/news/bnitem.aspx?name=63455946&source=genwire "Researchers Suggest Hormone Therapy for Prostate Cancer Can Cause Serious Heart Problems and Death"
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Gonadotropins and GnRH (G03G)
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Gonadotropin
preparations |
| Gonadotropins |
- Follicle-stimulating hormone
- Human chorionic gonadotropin
- Luteinizing hormone
- Menotropin
- Urofollitropin
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| Antigonadotropins |
- Sex steroids (via negative feedback on the HPG axis): Androgens (incl. anabolic steroids, e.g., nandrolone, oxandrolone)
- Estrogens
- Progestogens (incl., allylestrenol, chlormadinone acetate, cyproterone acetate, delmadinone acetate, dydrogesterone, medroxyprogesterone acetate, megestrol acetate, nomegestrol acetate, norethisterone acetate, progesterone, spironolactone)
- Steroid synthesis inhibitors: Danazol
- Gestrinone
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| GnRH analogues |
| Agonists |
- Buserelin
- Deslorelin
- GnRH (gonadorelin)
- Goserelin
- Histrelin
- Leuprorelin
- Nafarelin
- Triptorelin
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| Antagonists |
- Abarelix
- Cetrorelix
- Degarelix
- Ganirelix
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Index of reproductive medicine
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| Description |
- Anatomy
- Physiology
- Development
- sex determination and differentiation
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| Disease |
- Infections
- Congenital
- Neoplasms and cancer
- male
- female
- gonadal
- germ cell
- Other
- Symptoms and signs
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| Treatment |
- Procedures
- Drugs
- benign prostatic hypertrophy
- erectile dysfunction and premature ejaculation
- sexual dysfunction
- infection
- hormones
- androgens
- estrogens
- progestogens
- GnRH
- prolactin
- Assisted reproduction
- Birth control
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Assisted reproductive technology
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| Infertility |
- Female
- Male
- Fertility clinic
- Fertility testing
- Fertility tourism
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| Fertility medication |
- Estrogen antagonists
- aromatase inhibitor
- clomifene
- FSH
- GnRH agonists
- Gonadotropins
- hCG
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In vitro fertilisation (IVF)
and expansions |
- Assisted zona hatching
- Autologous endometrial coculture
- Cytoplasmic transfer
- Egg donation
- Embryo transfer
- Gestational carrier
- In vitro maturation
- Intracytoplasmic sperm injection
- Oocyte selection
- Ovarian hyperstimulation
- Preimplantation genetic diagnosis
- Transvaginal ovum retrieval
- Zygote intrafallopian transfer
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| Other methods |
- Artificial insemination
- Cryopreservation
- embryos
- oocyte
- ovarian tissue
- semen
- Gamete intrafallopian transfer
- Reproductive surgery
- Semen collection
- Sex selection
- Surrogacy
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| Donation |
- Donor registration
- Donor Sibling Registry
- Egg
- Embryo
- Sperm
- Sperm bank
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| Ethics |
- Accidental incest
- Religious response to ART
- Three-parent babies
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| In fiction |
- See subsection in sperm donation
- Reproduction and pregnancy in speculative fiction
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Index of reproductive medicine
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| Description |
- Anatomy
- Physiology
- Development
- sex determination and differentiation
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| Disease |
- Infections
- Congenital
- Neoplasms and cancer
- male
- female
- gonadal
- germ cell
- Other
- Symptoms and signs
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| Treatment |
- Procedures
- Drugs
- benign prostatic hypertrophy
- erectile dysfunction and premature ejaculation
- sexual dysfunction
- infection
- hormones
- androgens
- estrogens
- progestogens
- GnRH
- prolactin
- Assisted reproduction
- Birth control
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Index of obstetrics
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| Description |
- Pregnancy
- Development
- Anatomy
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| Disease |
- Pregnancy and childbirth
- Placenta and neonate
- Infections
- Symptoms and signs
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| Treatment |
- Procedures
- Drugs
- oxytocins
- labor repressants
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