A 35-year-old woman with endometriosis is prescribed a GnRH agonist (leuprolide acetate). In the first week of treatment, she experiences a transient worsening of pelvic pain. This initial flare is caused by which mechanism?

• A Direct inflammatory action of the drug on ectopic endometrial tissue
• B Paradoxical upregulation of estrogen receptors in endometrial implants
• C Initial stimulation of pituitary GnRH receptors causing a surge in LH and FSH, raising estradiol transiently ✓
• D Withdrawal of negative feedback causing rebound prostaglandin release from endometriotic lesions

Explanation

GnRH agonists initially stimulate pituitary gonadotrophs, causing an LH and FSH surge that transiently elevates estradiol before receptor downregulation causes suppression. This flare lasts approximately 1-2 weeks and can worsen symptoms of endometriosis or prostate cancer initially. GnRH antagonists (degarelix, cetrorelix) avoid this flare by directly blocking receptors without initial stimulation. Recognizing this flare phenomenon is clinically important for counseling patients.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.