A 22-year-old with 8 weeks of amenorrhoea seeks MTP. She is given mifepristone 200 mg orally followed 24–48 hours later by misoprostol 800 mcg vaginally. What is the mechanism by which mifepristone sensitises the uterus to misoprostol?

• A Mifepristone directly stimulates PGE2 synthesis in the myometrium
• B Mifepristone blocks oestrogen receptors, preventing oestrogen-mediated quiescence
• C Mifepristone directly inhibits placental hCG, causing progesterone withdrawal
• D Mifepristone increases oxytocin receptor expression and upregulates gap junction formation ✓

Explanation

Mifepristone is a competitive progesterone receptor antagonist (and partial glucocorticoid antagonist). Progesterone normally maintains uterine quiescence by suppressing gap junctions, reducing oxytocin receptors, and preventing prostaglandin production. Mifepristone's blockade of PR leads to: (1) upregulation of gap junctions (connexin 43) between myocytes — allowing coordinated uterine contractions; (2) upregulation of oxytocin and prostaglandin receptors, dramatically sensitising the uterus to the subsequent misoprostol (a PGE1 analogue). This synergism produces a complete abortion rate of ~97% at ≤63 days.

Reference: Williams Obstetrics, 26th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.