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Saturday, August 9, 2025

Gonadotropin releasing hormones


Generic and Brand Names

  • Leuprolide — Lupron, Eligard

  • Goserelin — Zoladex

  • Triptorelin — Trelstar, Decapeptyl

  • Histrelin — Supprelin LA, Vantas

  • Nafarelin — Synarel

  • Buserelin — Suprefact

  • Gonadorelin — Lutrepulse

Class

  • Hypothalamic decapeptide hormones regulating reproductive endocrine function

  • Also known as luteinizing hormone–releasing hormone (LHRH)

  • Therapeutic forms include natural GnRH (gonadorelin) and synthetic GnRH agonists (longer half-life, higher potency)

Mechanism of Action

  • Physiological role: Pulsatile secretion from the hypothalamus stimulates anterior pituitary GnRH receptors → release of LH and FSH → gonadal sex steroid production (estradiol, progesterone, testosterone)

  • Pulsatile administration (therapeutic): Mimics physiologic secretion → stimulates gonadotropin release (used in fertility treatment)

  • Continuous administration (therapeutic): Desensitizes and downregulates GnRH receptors → suppresses LH and FSH secretion → decreases gonadal sex steroids (medical castration or ovarian suppression)

Indications

Pulsatile Therapy (Gonadorelin)

  • Hypothalamic amenorrhea

  • Induction of ovulation in infertility due to hypothalamic GnRH deficiency

  • Delayed puberty due to GnRH deficiency

Continuous Therapy (GnRH Agonists)

  • Advanced hormone-dependent prostate cancer

  • Hormone-dependent breast cancer in premenopausal women

  • Endometriosis

  • Uterine fibroids

  • Precocious puberty

  • Ovarian suppression in assisted reproductive technology (ART) protocols

Dosage and Administration

Pulsatile GnRH (gonadorelin)

  • IV or SC via infusion pump delivering pulses every 60–90 minutes

  • Dose individualized (e.g., 5–20 mcg/pulse)

Continuous GnRH Agonists (leuprolide, goserelin, triptorelin, histrelin, nafarelin, buserelin)

  • SC or IM depot injections (monthly, 3-month, 6-month formulations depending on product)

  • Nasal spray formulations for some agents (e.g., nafarelin)

  • Example: Leuprolide 7.5 mg IM monthly for prostate cancer; higher or lower doses depending on indication

Monitoring

  • Oncologic use: Testosterone levels (men), estradiol levels (women)

  • Fertility use: LH, FSH, estradiol; follicular monitoring via ultrasound

  • Bone mineral density with long-term suppression therapy

  • Signs of disease progression or therapeutic effect

Contraindications

  • Hypersensitivity to GnRH or analogues

  • Pregnancy and breastfeeding

  • Undiagnosed abnormal vaginal bleeding

  • Hormone-sensitive tumors in pregnancy

  • For fertility use: Ovarian cysts not related to polycystic ovary syndrome

Precautions

  • Initial flare phenomenon (continuous agonists): Temporary rise in LH/FSH → increased sex steroid production → may worsen symptoms of hormone-dependent cancer or endometriosis initially; often co-administer antiandrogen in prostate cancer

  • Risk of bone mineral density loss with prolonged suppression

  • May cause hyperglycemia, cardiovascular risk changes with long-term androgen deprivation

  • Psychiatric effects: Mood changes, depression

  • In children: Monitor growth and puberty progression/regression as appropriate

Adverse Effects

Common (Continuous Use)

  • Hot flashes, night sweats

  • Decreased libido, erectile dysfunction (men)

  • Vaginal dryness, mood swings (women)

  • Injection site reactions

Long-Term

  • Osteoporosis, bone fractures

  • Metabolic changes (weight gain, insulin resistance, dyslipidemia)

Pulsatile Use

  • Ovarian hyperstimulation (with fertility induction)

  • Multiple pregnancies (with ART protocols)

Drug Interactions

  • Concurrent use with other hormonal agents may enhance or antagonize therapeutic effects

  • Estrogens/androgens/progestins may counteract suppression effects of continuous GnRH therapy

  • Additive bone loss risk with glucocorticoids or anticonvulsants

Overdose

  • Acute overdose is rare due to peptide nature and short half-life of natural GnRH

  • Symptoms from prolonged exposure: Excessive hormonal suppression, hypoestrogenism/hypoandrogenism symptoms

  • Management: Supportive; discontinue or adjust therapy

Patient Counselling

  • Explain difference between pulsatile and continuous therapy and their opposite effects

  • For continuous agonist therapy: Inform about initial flare and possible symptom worsening before improvement

  • Emphasize importance of adherence to dosing schedule for depot formulations

  • For fertility treatment: Stress close monitoring to prevent ovarian hyperstimulation syndrome (OHSS)

  • Advise on bone health: Weight-bearing exercise, adequate calcium/vitamin D

  • Report new or worsening mood changes, hot flashes, or signs of osteoporosis




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