DegarelixvsGonadorelin (GnRH)

Molecular Formula

C₈₂H₁₀₃ClN₁₈O₁₆

Molecular Weight

1632.3 Da

Half-Life

~53 days (median terminal half-life)

Bioavailability

100% (subcutaneous injection)

CAS Number

214766-78-6

Molecular Formula

C₅₅H₇₅N₁₇O₁₃

Molecular Weight

1182.3

Half-Life

2-4 minutes

Bioavailability

Varies by route: ~5-20% (intranasal), 100% (IV/IM injections)

CAS Number

34973-08-5

Common

• Mild discomfort at treatment site
• Injection site pain (28% of patients)
• Injection site redness or erythema (17%)
• Hot flashes (26% experience them)
• Increased liver enzymes and gamma-glutamyltransferase (10%)
• Weight gain (9%)
• Hypertension or elevated blood pressure (6%)
• Back pain (6%)
• Chills (5%)
• Constipation (5%)
• Urinary tract infection (5%)
• Injection site swelling (6%)
• Injection site induration or hardness (4%)
• Decreased sex drive and erectile dysfunction
• Gynecomastia (breast tissue growth)
• Testicular atrophy (shrinking)

Serious

• Severe allergic reaction

Common

• Mild headache
• Local injection site reactions (redness, swelling)
• Temporary hot flashes
• Mood changes or emotional sensitivity
• Nausea or mild stomach upset
• Allergic skin reactions
• Dizziness or lightheadedness
• Temporary changes in vision
• Joint or muscle aches
• Insomnia or sleep disturbances
• Severe allergic reactions (difficulty breathing, swelling)
• Severe hormonal imbalance symptoms
• Ovarian hyperstimulation syndrome (OHSS)
• Signs of blood clots (chest pain, leg swelling)
• Severe mood changes or depression

Serious

• Severe allergic reaction

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Degarelix is an FDA-approved GnRH antagonist with safety data from Phase 3 trials and post-market use in prostate cancer treatment. Advantages over GnRH agonists include absence of testosterone flare, allowing rapid castration without initial symptom surge. Primary safety concerns relate to intentional hormone suppression: hot flashes occur in 40-70% of men, erectile dysfunction in 40-60%, bone density loss of 2-3% annually, and cardiovascular risks in patients >65 years. Injection site reactions (erythema, induration) occur in 20-30% of patients and can be severe in a small percentage. Liver enzyme elevations appear in 5% of patients. QT prolongation potential exists and cardiac monitoring is recommended in susceptible patients.

Contraindications

• xHistory of severe hypersensitivity to degarelix
• xAllergy to any product components (mannitol or other additives)
• xActive untreated severe anaphylaxis risk

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

FDA approved for this use

Safety Overview

Gonadorelin is native GnRH and carries the safety profile established over 40+ years of clinical use in reproductive endocrinology. As the body's natural hormone, it produces minimal local side effects when dosed appropriately. The critical safety concern with gonadorelin is the initial flare effect within 24-48 hours of first dose—temporary elevation in FSH and LH—which can paradoxically suppress sex hormones before the desired stimulation occurs. This flare makes gonadorelin unsuitable for some conditions and explains why synthetic analogs (agonists, antagonists) are preferred in many modern fertility protocols.

Contraindications

• xPregnancy or breastfeeding
• xHormone-sensitive cancers (breast, prostate, ovarian)
• xSevere pituitary or hypothalamic disease
• xUndiagnosed abnormal vaginal bleeding
• xKnown hypersensitivity to GnRH