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Saturday, August 9, 2025

Gonadotropin-releasing hormone antagonists


Generic and Brand Names

  • Degarelix — Firmagon

  • Relugolix — Orgovyx

  • Cetrorelix — Cetrotide

  • Ganirelix — Antagon

  • Elagolix — Orilissa

  • Relugolix–Estradiol–Norethindrone — Myfembree (for uterine fibroids, endometriosis)

Class

  • Gonadotropin-releasing hormone (GnRH) receptor antagonists

  • Directly and competitively block GnRH receptors in the anterior pituitary

  • Rapid suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) without initial hormone surge

Mechanism of Action

  • Bind competitively to pituitary GnRH receptors

  • Inhibit release of LH and FSH → reduced gonadal sex steroid production (testosterone in men, estradiol in women)

  • In men: Suppress testosterone to castrate levels without initial flare seen with GnRH agonists

  • In women: Lower estradiol levels to reduce symptoms of endometriosis, uterine fibroids, or control ovulation timing in assisted reproductive technology (ART)

Indications

Oncology

  • Advanced hormone-dependent prostate cancer (degarelix, relugolix)

Gynecology / Reproductive Medicine

  • Prevention of premature LH surge during controlled ovarian stimulation for ART (cetrorelix, ganirelix)

  • Management of endometriosis-associated pain (elagolix, relugolix combinations)

  • Treatment of heavy menstrual bleeding due to uterine fibroids (elagolix combinations, relugolix combinations)

Dosage and Administration

Degarelix (Firmagon)

  • Initial: 240 mg SC as two 120 mg injections

  • Maintenance: 80 mg SC every 28 days

Relugolix (Orgovyx)

  • Loading: 360 mg orally once, then 120 mg orally daily

Cetrorelix (Cetrotide)

  • SC 0.25 mg daily during ovarian stimulation (short protocol) or 3 mg single dose for extended suppression

Ganirelix (Antagon)

  • SC 0.25 mg daily during controlled ovarian stimulation

Elagolix (Orilissa)

  • 150 mg orally once daily (up to 24 months) or 200 mg orally twice daily (up to 6 months) depending on indication and patient profile

Monitoring

  • Men: Serum testosterone to confirm castration levels (<50 ng/dL)

  • Women: Estradiol levels during therapy (in ART or chronic suppression)

  • Bone mineral density with long-term use (risk of bone loss)

  • Liver function tests (elagolix, relugolix)

  • ECG in patients with QT prolongation risk (relugolix)

Contraindications

  • Pregnancy (Category X for most agents)

  • Hypersensitivity to drug or excipients

  • Women with known osteoporosis (for chronic high-dose therapy)

  • Uncontrolled liver disease (elagolix, relugolix combinations)

Precautions

  • Bone mineral density loss with prolonged hypoestrogenism — consider add-back therapy (low-dose estrogen/progestin)

  • Cardiovascular risk: Androgen deprivation may increase CV events in men

  • Hepatic metabolism: Adjust dose or avoid in moderate–severe hepatic impairment for some oral agents

  • Fertility: Rapid return of fertility after discontinuation in women using for ART suppression — counsel accordingly

Adverse Effects

Men (oncology use)

  • Hot flashes, weight gain, fatigue, injection site reactions (degarelix)

  • Gynecomastia, decreased libido, erectile dysfunction

  • Potential metabolic changes (hyperglycemia, dyslipidemia)

Women (gynecologic use)

  • Hot flashes, night sweats, headache

  • Mood changes, insomnia

  • Vaginal dryness, decreased libido

  • Bone density reduction with prolonged use

  • Injection site redness/swelling (cetrorelix, ganirelix)

Drug Interactions

  • Oral agents (elagolix, relugolix): Substrates of CYP3A and P-gp — affected by strong inhibitors/inducers

  • Additive QT prolongation risk with other QT-prolonging drugs (relugolix)

  • Hormonal contraceptives containing estrogen may counteract therapeutic effect in gynecologic indications — use non-hormonal methods if contraception is required

Overdose

  • Symptoms: Exaggerated hypoestrogenic/androgen deprivation effects

  • Management: Supportive care; monitor hormone levels and clinical effects

Patient Counselling

  • Explain the purpose of therapy and expected hormonal suppression effects

  • For women: Discuss possible menstrual changes, bone loss risk, and need for add-back therapy if long-term use is planned

  • For men: Emphasize rapid testosterone suppression without flare, but possible side effects like hot flashes and sexual dysfunction

  • Take oral formulations at the same time daily; do not double dose if missed

  • Report new-onset depression, mood changes, or bone/joint pain

  • Maintain adequate calcium/vitamin D intake and weight-bearing exercise for bone health



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