Pharm

Gonadotropin-Releasing Hormone Agonist

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Gonadotropin-Releasing Hormone Agonist, Gonadotropin Releasing Hormone Agonist, Gonadotropin-Releasing Hormone Analog, GnRH Agonist, Gonadorelin, Nafarelin Acetate, Synarel, Leuprolide, Lupron, Goserelin, Zoladex, Histrelin, Vantas, Triptorelin, Trelstar

  • Indications
  1. Endometriosis
    1. Nafarelin Acetate (Synarel)
    2. Leuprolide (Lupron)
    3. Goserelin (Zoladex)
  2. Central Precocious Puberty
    1. Nafarelin Acetate (Synarel)
    2. Leuprolide (Lupron)
    3. Histrelin (Vantas)
    4. Triptorelin (Trelstar)
  3. Uterine Fibroids
    1. Leuprolide (Lupron)
  4. Prostate Cancer (Men with regionally advanced or metastatic cancer)
    1. Leuprolide (Lupron)
    2. Goserelin (Zoladex)
    3. Histrelin (Vantas)
  • Contraindications
  1. Pregnancy
  • 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 Agonist
    1. GnRH Agonists are synthetic analogs of GnRH
    2. When GnRH (e.g. Gonadorelin) is given in IV pulses, 90 min apart, they trigger Ovulation
      1. Pulsatile GnRH release mimics in vivo GnRH release that triggers FSH and LH release
      2. May be used in Female Infertility due to central Hypogonadism to trigger Ovulation
    3. When GnRH Agonists are used continuously they disrupt normal pulsatile release of GnRH
      1. Hyperstimulates receptors (with initial transient increase in LH and FSH release)
      2. Results in Desensitization and down regulation of GnRH receptors
      3. Ultimately decreases LH and FSH release from the pituitary
      4. Results in hypoestrogenism or pseudo-Menopause and is used in Prostate Cancer and Endometriosis
  3. Images
    1. hypothalamusPituitaryHormones.png
  • Medications
  1. Leuprolide (Lupron)
  2. Goserelin (Zoladex)
  3. Histrelin (Vantas)
  4. Triptorelin (Trelstar)
  5. Nafarelin Acetate (Synarel)
    1. Endometriosis
      1. Dose 200 mg (1 spray) micro-g intranasally twice daily (alternating nostrils)
      2. Duration: 6 months
    2. Central Precocious Puberty
      1. Dose 2 sprays in each nostril twice daily (800 mcg twice daily)
  • Dosing
  1. See other references
  • Efficacy
  1. Endometriosis (Nafarelin)
    1. Effective at regression of lesions and relief of pain
    2. Does not cause the same androgenic effects as Danazol
    3. No proven effect on fertility
  • Adverse Effects
  • Women
  1. Menopausal symptoms
    1. Hot Flashes
    2. Insomnia
    3. Emotional changes (includes Major Depression)
  2. Bone density loss with prolonged use
    1. Consider add-back therapy with Norethindrone to reduce bone loss risk
  3. Ovarian Cysts
    1. May develop in first 2 months of medication use
  4. Other effects
    1. Vaginal Bleeding (initial first 1-2 months)
    2. Weight gain
    3. Fatigue
    4. Hyperglycemia
    5. Dyslipidemia
    6. Cognitive effects (decreased mental sharpness)
    7. QTc Prolongation (Leuprolide)
  1. Prostate Cancer initial flare
    1. Occurs with initial, transient increase in Testosterone
  2. Hot Flashes
  3. Erectile Dysfunction
  4. Testicular atrophy
  5. Gynecomastia
  6. Alopecia
  7. Other effects (similar to women)
    1. Weight gain
    2. Fatigue
    3. Hyperglycemia
    4. Dyslipidemia
    5. Cognitive effects (decreased mental sharpness)
  • Safety
  1. Pregnancy Category X
    1. Use reliable Contraception
  2. Avoid in Lactation
  • Resources
  1. Nafarelin Acetate (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0aa57cb-d2f4-46d7-af43-7c8b06aa81a6
  2. Leuprolide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bec9077a-3f04-4887-856d-dde2de24584d
  3. Goserelin (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4cb3c20-2738-400a-b522-3f36f71fe6c5
  4. Histrelin (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8fb000e-3cc9-4803-b71d-2cc597661977
  5. Triptorelin (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f41380e7-b830-432d-a5f5-a872932f107e
  • 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]