Generic Name

Triptorelin

Mechanism

• GnRH receptor agonist: Binds to *GnRH receptors* on anterior pituitary gonadotrophs.
• Initial stimulation: Causes transient surge (“flare”) of LH/FSH release, ↑ testosterone/estrogen production.
• Desensitization and down‑regulation: Continuous exposure leads to receptor desensitization → ↓ LH/FSH secretion over 2–4 weeks.
• Outcome: ↓ gonadal steroidogenesis (testosterone or estradiol) → castration‑level hormones.

Pharmacokinetics

Indications

• Prostate cancer (hormone‑dependent) – to achieve castrate‑level testosterone.
• Endometriosis (painful pelvic disease).
• Uterine fibroids (size reduction, symptom relief).
• Precocious puberty (delaying gonadal maturation).
• Gonadal suppression pre‑fertility preservation (e.g., in cancer therapy).
• Human papillomavirus (HPV) reactivation prophylaxis in some protocols.

Contraindications

• Known hypersensitivity to triptorelin or any excipients.
• Castration‑sensitive prostate cancer if no initial flare‑prevention.
• Females pregnant/breastfeeding – teratogenic potential unknown.
• Severe liver impairment – reduced metabolism may elevate levels.
• Severe renal impairment – may prolong drug action.
• Active adrenal crisis or end‑stage urosepsis – avoid unless benefits outweigh risks.

Warnings
• Flare reaction: ↑ testosterone/estrogen surge; consider pre‑treatment with anti‑androgen or estrogen blockade in prostate cancer.
• Hypogonadism‑related symptoms: hot flashes, sexual dysfunction, osteoporosis risk.
• Hyponatremia: especially in elderly or those on diuretics.
• Pituitary adenomas: may unmask or worsen disease.

Dosing

• Prostate cancer: 3.75 mg SC every 4 weeks (initial 1.92 mg SC after 0.5 mg oral leuprolide).
• Endometriosis & fibroids: 3.75–4.5 mg SC every 4 weeks or 3.75 mg SC every 28 days (monthly).
• Precocious puberty (children): 0.1 mg (0.3 mg/m²) SC monthly, titrated.
• Depot (30 mg) for 3 months: 30 mg IM/SC, interval 3 months (often used in prostate cancer).
• Route: Subcutaneous or intramuscular.
• First dose protocol – For prostate cancer, combine with short‑acting anti‑androgen for 1–2 weeks to blunt flare.

Monitoring

• Baseline: LH, FSH, testosterone/estradiol, PSA (men), estradiol (women), bone mineral density (BMD) if prolonged therapy.
• During therapy:
• PSA every 3–6 weeks (prostate cancer).
• Serum LH/FSH (to confirm suppression).
• BMD every 1–2 years (≥1‑year therapy).
• Adverse‑effect surveillance: Monitor for hot flashes, bone pain, hyponatremia (serum sodium).
• Imaging: Pelvic MRI/US for fibroids/endometriosis size; pituitary MRI if neurological symptoms.

Clinical Pearls

1. Flare‑Prevention: In prostate cancer, give an oral anti‑androgen (bicalutamide 50 mg bid × 3 days) before and during the first month of triptorelin to mitigate testosterone surge.
2. Depot Flexibility: 30 mg IM formulation reduces clinic visits; however, verify patient compliance when switching to monthly injections.
3. Bone Health Strategy: Concurrent calcium, vitamin D, and bisphosphonate or denosumab should be considered after 6 months of therapy.
4. Hyponatremia Awareness: Triploid‑leptin can potentiate SIADH; check sodium in patients on thiazides or SSRIs.
5. Reversibility: Hormonal suppression is largely reversible within 3–6 months after drug cessation—key for fertility considerations in young patients.
6. Adolescents: Use weight‑based dosing and monitor growth velocity to avoid accelerated skeletal maturation.

By integrating these key points, clinicians can optimize therapeutic outcomes while minimizing adverse events associated with triptorelin therapy.