A 55-year-old man with advanced prostate cancer is started on a GnRH agonist (leuprolide). Before adding an anti-androgen, the clinician warns of an initial 'testosterone flare'. What is the mechanism of this flare?

• A Direct stimulation of testicular Leydig cells by leuprolide
• B Initial transient agonist action at pituitary GnRH receptors causing LH surge ✓
• C Upregulation of androgen receptors in the prostate during the first week
• D Inhibition of 5-alpha reductase leading to testosterone accumulation

Explanation

GnRH agonists initially stimulate pituitary GnRH receptors, causing a transient surge in LH and testosterone before receptor downregulation occurs. This flare can worsen symptoms in prostate cancer, so an anti-androgen is given for the first 2-3 weeks. GnRH antagonists (degarelix) avoid this flare by directly blocking the receptor without initial stimulation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.