Generic Name

Leuprolide

Mechanism

• Leuprolide is a synthetic GnRH (gonadotropin‑releasing hormone) agonist that mimics endogenous GnRH.
• Continuous stimulation of the GnRH receptors on pituitary gonadotrophs leads to:
• Initial flare‑up of LH and FSH release (2‑8 days).
• Subsequent down‑regulation of GnRH receptors, causing a profound ↓ in pituitary LH/FSH levels.
• The resulting suppression of gonadal steroid production (testosterone, estrogen, progesterone) produces therapeutic effects in hormone‑driven conditions.

Pharmacokinetics

• Routes: Intramuscular (IM) injection (depot) or transdermal (patch) for certain formulations.
• Absorption: Depot IM (1 mg, 3.75 mg, 7.5 mg) releases drug over 4–12 weeks; patch releases ~1.8 mg per day.
• Distribution: Large Vd due to depot implantation; protein binding ~60‑70 %.
• Metabolism: Minimal hepatic metabolism; mainly excreted unchanged.
• Half‑life: ~5–7 days (depot); ~1–2 days (patch).
• Elimination: Primarily renal (≈90 % unchanged).
• Special populations: No adjustment needed in mild‑to‑moderate renal impairment; safety data limited for severe renal disease.

Indications

• Androgen‑dependent prostate cancer – medical castration.
• Pre‑surgical estrogen reduction in breast cancer.
• Treatable precocious puberty in pediatrics.
• Endometriosis – menstrual suppression.
• Uterine fibroids (as part of hormonal management).
• Gonadal‑stimulation suppression in assisted reproduction protocols.
• Hypogonadism – short‑term temporary gonadotrophic suppression.

Contraindications

• Contraindications:
• Known hypersensitivity to leuprolide or any excipient.
• Baseline androgen deficiency (e.g., advanced liver disease with hypogonadism).
• Active uncontrolled infection at injection site.
• Warnings:
• Initial testosterone flare → risk of worsening prostate‐related symptoms; mitigate with anti‑androgen (e.g., bicalutamide) if needed.
• Osteoporosis: long‑term use depresses bone mineral density; consider bisphosphonate or calcium/vitamin D supplementation.
• Cardiovascular: rare but potential for gynecomastia, hypertension, edema.
• Depression and emotional lability reported in some patients.

Dosing

• Administration: Inject in the gluteal muscle (deep deposition).
• Patch placement: Upper abdomen or thighs; rotate sites every 24 h.
• Storage: 2–8 °C; freeze >32 °C.
• Handling: Use aseptic technique; discard unused aliquots per product SDS.

Adverse Effects

• Common:
• Hot flashes, night sweats
• Decreased libido
• Injection site pain/induration
• Headache, dizziness
• Mood swings
• Exacerbated estrogenic nausea (when used pre‑operatively).
• Serious / Rare:
• Osteopenia/osteoporosis (≥6 months) → fractures
• Severe allergic reactions (anaphylaxis)
• Seropsitivity for anti‑GnRH antibodies (rare).
• Cardiac arrhythmias in predisposed individuals.
• Emergency: severe flare in prostate cancer—consider anti‑androgen co‑therapy.

Monitoring

• Baseline:
• PSA (prostate cancer)
• Bone mineral density (BMD) if >12 months therapy
• Serum LH/FSH, testosterone/estradiol levels.
• Periodic:
• PSA every 3–6 months (prostate).
• BMD every 12 months if >2 yrs therapy.
• Serum calcium, phosphate, renal function quarterly (patch).
• Clinical exam for gynecomastia, edema, depression.

Clinical Pearls

• Flare‑Throttle Strategy: For men with significant prostate disease, co‑administer a non‑steroidal anti‑androgen (bicalutamide 150 mg daily) for the first 2–3 weeks to blunt testosterone flare.
• Bone Protection: Combine leuprolide with bisphosphonates (e.g., alendronate) or denosumab if baseline T-score ≤‑1.0.
• Patch‑Specific Tip: Patch sites should be changed in the opposite quadrant to avoid "patch fatigue" and increase absorption.
• Pediatric Precocious Puberty: Dose adjustment to body‑weight (0.1 mg/kg) yields rapid suppression; monitor growth velocity and bone age.
• Drug‑Interaction Awareness: Anti‑epileptics (e.g., phenytoin) and estrogens can blunt endocrine suppression; adjust dosage accordingly.
• Reversal After Therapy: Discontinuation of leuprolide typically leads to resumption of gonadal function within 1–3 months; plan fertility counseling if desired.

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