NafarelinvsLeuprolide

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

C₅₉H₈₄N₁₆O₁₂

Molecular Weight

1209.4 g/mol

Half-Life

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

Bioavailability

~95% (subcutaneous injection)

CAS Number

74381-53-6

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

• Hot flashes (very common in men)
• Decreased libido and erectile dysfunction
• Injection site pain or swelling
• Nausea
• Fatigue
• Mood changes or depression
• Joint or muscle pain
• Headaches
• Dizziness
• Thinning hair
• Decreased bone density (osteoporosis with long-term use)
• QT prolongation (rare but serious cardiac effect)
• Tumor flare (temporary worsening of cancer symptoms in first weeks)
• Severe allergic reactions
• Spinal cord compression risk in men with metastatic disease

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

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Leuprolide (Lupron) is an FDA-approved GnRH agonist with 35+ years of clinical safety data involving millions of patients in oncology and endocrinology. The critical safety issue is the initial 5-7 day flare effect—temporary surge in FSH/LH causing symptom worsening before hormone suppression begins—particularly dangerous for prostate cancer patients (flare can cause urinary obstruction or spinal cord compression). Bone density loss is a dose-dependent long-term risk in both men and women requiring monitoring. Injection site reactions, hot flushes, and initial hypogonadal symptoms are expected and typically transient.

Contraindications

• xPregnancy or breastfeeding (teratogenic)
• xUndiagnosed vaginal bleeding
• xActive bone metastases with spinal cord compression (increased fracture risk)
• xAllergy to GnRH agonists or components
• xSevere cardiovascular disease with QT prolongation risk