A 68-year-old man with metastatic prostate cancer is started on leuprolide, a GnRH agonist. In the first 1-2 weeks of therapy, he experiences worsening bone pain. The mechanism underlying this initial clinical deterioration is:

• A Direct tumor flare due to leuprolide stimulating prostate cancer cell proliferation
• B Adrenal androgen surge due to leuprolide-induced ACTH stimulation
• C Initial stimulation of LH and FSH release causing a transient rise in testosterone ✓
• D Inflammatory cytokine release from tumor necrosis triggered by leuprolide

Explanation

GnRH agonists like leuprolide cause an initial surge in LH and FSH release before receptor downregulation occurs. This produces a transient testosterone flare lasting 1-2 weeks, which can worsen symptoms in metastatic disease. For this reason, anti-androgens such as bicalutamide are often co-prescribed for the first 2-3 weeks to block the flare effect. This is a well-established clinical pearl in prostate cancer management.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.