NafarelinvsGonadorelin (GnRH)

Molecular Formula

C₆₆H₈₃N₁₇O₁₃

Molecular Weight

1322.5 g/mol

Half-Life

Approximately 2-6 hours (varies by route of administration)

Bioavailability

~2-3% (intranasal)

CAS Number

86220-42-0

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

• Hot flashes and night sweats (happen in 90% of users)
• Mood changes including depression or anxiety
• Decreased sexual interest
• Vaginal dryness
• Headaches
• Nasal irritation (if using spray formulation)
• Breast tenderness
• Muscle aches and joint pain
• Weight gain or changes in body composition
• Nausea and upset stomach
• Sleep problems
• Emotional sensitivity and mood swings
• Allergic reactions (rare)
• Significant bone density loss with extended use
• Severe mood disorders requiring medical attention
• Hot flashes (flushes of heat and redness)
• Night sweats and chills
• Vaginal dryness and discomfort
• Mood depression or anxiety
• Changes in sexual desire
• Weight changes
• Headaches
• Muscle and joint aches
• Nasal irritation or sinus problems
• Breast tenderness or swelling
• Acne
• Sleep disturbances
• Nausea
• Fatigue
• Bone pain

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

Nafarelin is FDA-approved with a well-established safety profile across decades of clinical use for endometriosis and precocious puberty. The most significant safety consideration is hypogonadism and bone density loss during prolonged therapy, requiring add-back therapy (norethindrone 0.4 mg daily) after 6 months to prevent osteoporosis. Common side effects—hot flashes, vaginal dryness, mood changes—are reversible upon discontinuation and typically diminish with continued use.

Contraindications

• xPregnancy (can harm fetus - must use non-hormonal birth control)
• xHypersensitivity to GnRH agonists
• xUndiagnosed vaginal bleeding
• xSevere osteoporosis or bone disease

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