Leuprolide is a gonadotropin-releasing hormone (GnRH) agonist used in oncology, endocrinology, and reproductive medicine. It works by initially stimulating, then suppressing, the pituitary release of LH and FSH, leading to reduced sex hormone production (estrogen in females, testosterone in males).
Pharmacological Class
- GnRH agonist (synthetic analog of naturally occurring gonadotropin-releasing hormone)
Mechanism of Action
- Initial phase (“flare”): Stimulates pituitary GnRH receptors → transient increase in LH & FSH → increased sex hormones.
- Chronic phase (after ~1–3 weeks): Continuous stimulation causes downregulation of GnRH receptors → suppressed LH & FSH secretion → decreased estrogen & testosterone production.
- Result: medical castration (reversible upon discontinuation).
Oncology Indications
- Prostate cancer (androgen deprivation therapy)
- Breast cancer (premenopausal women with hormone receptor–positive tumors, usually with an aromatase inhibitor or tamoxifen)
- Endometrial cancer (selected cases)
Non-Oncology Indications
- Endometriosis
- Uterine fibroids
- Central precocious puberty
- Fertility preservation (ovarian suppression during chemotherapy)
Oncology Dosing Examples
- Prostate cancer:
- 7.5 mg IM monthly
- 22.5 mg IM every 3 months
- 45 mg IM every 6 months
- Breast cancer ovarian suppression:
- 3.75 mg IM monthly or 11.25 mg IM every 3 months
- Dose depends on depot formulation used.
Adverse Effects
- Short-term (flare period): Bone pain, tumor flare, hot flashes.
- Long-term: Osteoporosis, decreased libido, erectile dysfunction, vaginal dryness, mood changes, metabolic changes.
- Injection site reactions.
Key Clinical Considerations for Oncology Pharmacists
- In prostate cancer, consider antiandrogen pre-treatment (e.g., bicalutamide) to prevent flare symptoms in metastatic disease.
- In premenopausal breast cancer, always combine with an aromatase inhibitor or tamoxifen—never use alone.
- Monitor bone density with long-term use; supplement calcium/vitamin D ± bisphosphonates if needed.
- Counsel on menopausal symptoms and fertility effects.
- In fertility preservation during chemotherapy: start before chemotherapy and continue during treatment to reduce ovarian toxicity (evidence stronger in hormone-negative cancers).