Generic Name

Lupron

Mechanism

Lupron (leuprolide acetate) is a potent, synthetic gonadotropin‑releasing hormone (GnRH) agonist.
• Initial effect: Immediate stimulation of pituitary GnRH receptors → ↑ LH and FSH → transient surge of sex steroids.
• Desensitization phase: Continuous exposure leads to receptor down‑regulation, resulting in profound suppression of luteinizing hormone (LH), follicle‑stimulating hormone (FSH), and consequently estradiol/testosterone levels.
• Therapeutic outcome: Lowered gonadal hormone production → decreased tumor growth in prostate cancer, reduction of estrogen‑driven endometriosis and uterine fibroids, and suppression of puberty in children.

Pharmacokinetics

• Absorption: Intramuscular depot releases leuprolide slowly; peak serum levels ~1 month after injection.
• Distribution: Highly protein‑bound (~30 % to plasma proteins).
• Metabolism: Occurs primarily in the liver via various cytochrome P450 isoforms; no major active metabolites.
• Elimination: Half‑life ranges from 9.5 days (short‑acting) to 32 days (depot), with total elimination over 3–4 months.
• Drug interactions: Concomitant use with steroids or antipsychotics can blunt receptor down‑regulation; no significant CYP inhibition/induction noted.

Indications

• Advanced, castration‑resistant prostate cancer: ≥3 months of therapy; schedules: 3.75 mg IM monthly, 7.5 mg IM bi‑monthly, or 3.75 mg IM every 6 weeks.
• Hormone‑dependent disorders of the female reproductive tract:
• Endometriosis (12 months therapy)
• Uterine fibroids (≤12 months)
• Menorrhagia related to hormonal imbalance
• Precocious puberty in children (where no other first‑line therapy is viable).
• Retro‑rectal prostate‑Siccas therapy (specialized use).

Contraindications

• Hypersensitivity to leuprolide, GnRH agonists, or any formulation component.
• Active hepatic disease (elevated transaminases >3× ULN).
• Adrenal insufficiency (history of hypoadrenalism).
• Severe osteoporosis or osteopenia (risk of fractures due to bone density loss).
• Pregnancy / lactation (teratogenic risk: fetal hypogonadism).
• Severe cardiovascular disease (increased risk of myocardial ischemia with testosterone suppression).
• Concurrent use of exogenous steroids may mask adrenal suppression; caution advised.

Dosing

• Prostate cancer:
• 3.75 mg IM every month (3‑month or 6‑month reusable devices).
• 7.5 mg IM every 2 months (alternative for patients who prefer less frequent visits).
• Endometriosis / fibroids: 3.75 mg IM every 4 weeks; maximum of 12 weeks for fibroids, 12 months for endometriosis.
• Precocious puberty: 7.5 mg IM every 4 weeks; follow‑up at 3 months.
• Route: Deep intramuscular injection into gluteal muscle; always rotate sites.
• Storage: Store below 30 °C; protect from light.

Adverse Effects

• Common:
• Hot flashes / night sweats (≈60 %)
• Injection site reactions (pain, erythema)
• Headache
• Mood changes (depression, anxiety)
• Decreased libido
• Serious:
• Osteoporosis / osteopenia → fractures (≈5 % at 12 months)
• Cardiovascular events (myocardial infarction, stroke) – cumulative risk in older males
• Adrenal insufficiency (especially post‑pulsatile flare)
• Severe allergic reactions (rash, anaphylaxis)
• Gastrointestinal disturbances (abdominal pain, nausea)

Monitoring

• Baseline: PSA, serum testosterone, liver enzymes, complete blood count, serum electrolytes, and bone density (DXA).
• During therapy:
• PSA (every 3 months for prostate cancer)
• Serum testosterone (every 6 months)
• Bone mineral density (DXA) annually or sooner if symptomatic
• Liver function tests (every 6 months)
• Full metabolic panel (electrolytes, renal function) periodically
• Monitor for signs of adrenal insufficiency (fatigue, hypotension)
• Post‑therapy: Re‑establish androgen levels; evaluate for recovery of gonadal function.

Clinical Pearls

• Initial flare management: For patients with prostate cancer, pre‑treat with a short‑acting GnRH antagonist (e.g., degarelix) for 2‑3 days to blunt the testosterone surge.
• Bone health: Single‑board approach; baseline DXA and bisphosphonate/denosumab initiation for patients with T‑score ≤ −1.0.
• Intermittent therapy: In select prostate cancer patients, consider an intermittent dosing schedule to reduce hot‑flash burden and preserve bone density while maintaining oncological control.
• Correct timing of injections: Schedule the next dose 1 week before the 4‑week interval to avoid premature hormone recurrence.
• Administration technique: Rotate gluteal sites and use a 1‑inch needle to prevent tissue injury.
• Patient education: Emphasize adherence; counsel on possible emotional changes and encourage prompt reporting of severe flare symptoms.

Note: This drug card summarizes current evidence and should complement clinical guidelines and local protocols.