Gonadotropin-Releasing Hormone Antagonist

Aka: Gonadotropin-Releasing Hormone Antagonist, Gonadotropin Releasing Hormone Antagonist, GnRH Antagonist, LHRH Antagonist, Degarelix, Firmagon, Relugolix, Orgovyx, Elagolix, Orilissa, Abarelix, Plenaxis, Ganirelix, Fyremadel, Antagon, Cetrorelix, Cetrotide

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II. Indications

  1. Fertility Treatment - Inhibits premature LH surge in controlled Ovarian Hyperstimulation (women)
    1. Ganirelix (Fyremadel, Antagon)
    2. Cetrorelix (Cetrotide)
  2. Endometriosis (moderate to severe pain in women)
    1. Elagolix (Orilissa)
  3. Advanced Prostate Cancer (Men)
    1. Degarelix (Firmagon)
    2. Relugolix (Orgovyx)
    3. Abarelix (Plenaxis)

III. Contraindications

  1. Pregnancy
  2. Osteoporosis
  3. Severe liver disease (Elagolix)

IV. Mechanism

  1. Gonadotropin-Releasing Hormone (GnRH)
    1. GnRH is generated within hypothalamic Neurons (infundibular nucleus, arcuate nucleus)
    2. GnRH is released typically in pulses in men and women
      1. GnRH is also released in a surge before Ovulation
    3. GnRH binds receptors on the Pituitary Gland triggering release of gonadotropins
      1. Luteinizing Hormone (LH)
      2. Follicle Stimulating Hormone (FSH)
    4. Gonadotropins (LH, FSH) stimulate release of sex Hormones (e.g. Estrogen, Testosterone)
  2. GnRH Antagonist
    1. GnRH Antagonists are synthetic peptides that block GnRH receptors on the surface of Gonadotroph cells in the anterior pituitary
    2. Decrease LH and FSH release from the anterior Pituitary Gland's Gonadotroph cells
    3. Results in decreased Estrogen synthesis (ovaries) and Testosterone synthesis (Testes)
  3. Images
    1. hypothalamusPituitaryHormones.png

V. Medications: Women

  1. Elagolix (Orilissa)
    1. Endometriosis: 150 mg orally once daily (<=24 months, <=6 months in liver disease) or 200 mg orally twice daily (<=6 months)
  2. Ganirelix (Fyremadel, Antagon)
    1. Infertility: Start day 5-6 of cycle (after FSH therapy on Day 2-3), giving 250 mcg SQ daily during the mid-late Follicular Phase
  3. Cetrorelix (Cetrotide)
    1. Infertility: Start day 5-6 of cycle (after FSH therapy on Day 2-3), giving 0.25 mcg SQ daily during the mid-late Follicular Phase

VI. Medications: Prostate Cancer (Men)

  1. Degarelix (Firmagon)
    1. Prostate Cancer: Start with 240 mg SQ, then 80 mg SQ every 28 days
  2. Relugolix (Orgovyx)
    1. Prostate Cancer: Start with 360 mg orally day 1, then 120 mg orally daily at same time each day
  3. Abarelix (Plenaxis)
    1. Older agent, replaced by newer agents (e.g. Degarelix)

VII. Adverse Effects: Women

  1. Menopausal symptoms
    1. Hot Flashes
    2. Insomnia
    3. Emotional changes (includes Major Depression)
  2. Liver Function Test abnormalities (Elagolix)
    1. Increased transaminases
  3. Bone density loss with prolonged use
  4. Other adverse effects
    1. Headache
    2. Nausea
    3. Arthralgias

VIII. Adverse Effects: Prostate Cancer (Men)

  1. Hypersensitivity including Anaphylaxis (Degarelix, Relugolix)
  2. QTc Prolongation (Degarelix, Relugolix)
  3. Bone density loss with prolonged use
  4. Liver Function Test abnormalities (Degarelix, Relugolix)
    1. Increased transaminases
  5. Other adverse effects
    1. Injection site reactions (Degarelix)
    2. Hot Flashes
    3. Altered bowel habits (Relugolix)
    4. Musculoskeletal pain (Relugolix)

IX. Safety

  1. Avoid in Pregnancy
  2. Avoid in Lactation

X. Drug Interactions

  1. Strong P-gp Inhibitors (esp. combined with strong CYP3A Inducers)
    1. Avoid with Relugolix (or separate doses by at least 6 hours)
  2. OATP 1B1 Inhibitors
    1. Avoid with Elagolix (significantly increases drug levels)

XI. Resources

  1. Degarelix (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab11dd8a-0fd9-4013-89ab-e114557c7e4b
  2. Relugolix (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=077a92f6-9f1b-479a-87c7-c92b5db6aa9c
  3. Elagolix (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a86757b3-09c5-fd3b-1223-244e94f50a66
  4. Ganirelix (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=32fb74ff-993a-49fe-8943-e029372b863e
  5. Cetrorelix (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=aca7768e-28a7-4027-b1d8-e66247665f79

XII. References

  1. (2022) Presc Lett, Medications to treat Prostate Cancer, Resource #380108
  2. Fairchild (2015) AJR Am J Roentgenol 204(6):W620-30 +PMID: 26001251 [PubMed]

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Related Studies

Cost: Medications

orilissa (on 10/12/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ORILISSA 150 MG TABLET $36.15 each
ORILISSA 200 MG TABLET $18.11 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Ontology: ganirelix (C0073629)

Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH C061018
SnomedCT 326088005, 395728002
English D-Alaninamide, N-acetyl-3-(1-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-L-tyrosyl-N6-(bis(ethylamino)methylene)-D-lysyl-L-leucyl-N6-(bis(ethylamino)methylene)-L-lysyl-L-prolyl-, GnRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Et2-hArg(6,8)-AlaNH2(10)-, LHRH, N-acetyl-2-naphthylalanyl(1)-(4-chlorophenylalanyl)(2)-3-pyrdinylalanyl(3)-diethylhomoarginyl(6,8)-alaninamide(10)-, N-Ac-(2-naphthyl)Ala-2-(4-Cl-Phe)-3-(3-pyridinyl-Ala)-6,8-Et2-hArg-10-AlaNH2-LHRH, ganirelix, LHRH,N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Et2-hArg(6,8)-AlaNH2(10)-, ganirelix [Chemical/Ingredient], Ganirelix (product), Ganirelix (substance), Ganirelix, GANIRELIX
Spanish ganirelix (producto), ganirelix (sustancia), ganirelix
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: cetrorelix (C0209366)

Definition (NCI) Cetrorelix is a synthetic decapeptide which is structurally related to gonadotrophin-releasing hormone (luteinising-hormone releasing hormone). It acts as an LHRH antagonist. (from ASTA Medica)
Definition (NCI_NCI-GLOSS) A synthetic luteinizing hormone-releasing hormone (LH-RH) antagonist that suppresses LH and sex steroid levels.
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH C062876
SnomedCT 326083001, 395906005
English LHRH, N-Ac-1-Nal(2)-2-Phe(pCl)-3-Pal(3)-6-Cit-10-Ala-, LHRH, N-acetyl-1-(3-(2-naphthyl)alanyl)-2-(4-chlorophenylalanyl)-3-(3-(3-pyridyl)alanyl)-6-citrulline-10-alanine-, N-acetyl-1-(3-(2-naphthyl)alanine)-2-(4-chlorophenylalanine)-3-(3-(3-pyridyl)alanine)-6-citrulline-10-alanine-LHRH, cetrorelix, cetrorelix [Chemical/Ingredient], CETRORELIX, Cetrorelix (product), Cetrorelix (substance), Cetrorelix
Spanish cetrorelix (producto), cetrorelix (sustancia), cetrorelix
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: abarelix (C0965390)

Definition (NCI_NCI-GLOSS) A drug used to reduce the amount of testosterone made in patients with advanced symptomatic prostate cancer for which no other treatment options are available. It belongs to the family of drugs called gonadotropin-releasing hormone (GnRH) antagonists.
Definition (NCI) A synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth.
Definition (PDQ) A synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=415570&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=415570&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2015" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH C423508
SnomedCT 407128008, 407129000
English ABARELIX @ @ UNIDENTIFIED, ABARELIX UNIDENTIFIED, gonadotropin releasing hormone antagonist abarelix, abarelix (medication), N-acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-N-methyl-L-tyrosyl-D-asparaginyl-L-leucyl-N(6)-(1-methylethyl)-L-lysyl-L-prolyl-D-alaninamide, abarelix [Chemical/Ingredient], abarelix, Abarelix, Abarelix (product), Abarelix (substance), ABARELIX
Spanish abarelix (producto), abarelix (sustancia), abarelix
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Gonadotropin releasing hormone antagonist (C1268855)

Definition (NCI) A synthetic peptide that competes with the neurohormone GnRH for its receptor, thus decreasing or blocking GnRH action. As a result endogenous pituitary output of FSH and LH is shut down.(Wikipedia)
Concepts Hormone (T125) , Pharmacologic Substance (T121)
SnomedCT 395962005, 116101001
English gonadotropin releasing hormone antagonists (GNRH-AN), gonadotropin releasing hormone antagonists (GNRH-AN) (medication), Gonadotropin Releasing Hormone Inhibitor, GnRH Antagonist, Gonadotropin Releasing Hormone Antagonist, Gonadotrophin releasing hormone antagonist, Gonadotropin releasing hormone antagonist, Gonadotropin releasing hormone antagonist (product), Gonadotropin releasing hormone antagonist (substance)
Spanish antagonista de GNRH, antagonista de hormona liberadora de gonadotrofinas (producto), antagonista de hormona liberadora de gonadotrofinas (sustancia), antagonista de hormona liberadora de gonadotrofinas, antagonista de hormona liberadora de gonadotropinas
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: degarelix (C1455035)

Definition (NCI) A long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes.
Definition (NCI_NCI-GLOSS) A drug that is used to treat advanced prostate cancer and is also being studied in the treatment of benign prostatic hyperplasia. Degarelix binds to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland. This causes the body to stop making testosterone, which prostate cancer needs to grow. Degarelix is a type of GnRH antagonist.
Definition (PDQ) A long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=441235&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=441235&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48385" NCI Thesaurus)
Concepts Hormone (T125) , Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C431566
SnomedCT 441864003, 441758000
English N-acetyl-3-(naphtalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-L-seryl-4-((((4S)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-L-leucyl-N6-(1-methylethyl)-L-lysyl-L-prolyl-D-alaninamide, degarelix, DEGARELIX, Degarelix (substance), Degarelix (product), Degarelix
Spanish degarelix, degarelix (producto), degarelix (sustancia)
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: elagolix (C2714632)

Concepts Organic Chemical (T109)
MSH C539351
English elagolix
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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