Chlormadinone acetate suppresses prostaglandin biosynthesis in human endometrial explants

ObjectiveTo elucidate the mode of action of chlormadinone acetate (CMA) in reducing dysmenorrheic pain by studying the effects of CMA and dexamethasone (DEX) on messenger RNA (mRNA) abundance of cyclo-oxygenase-2 (COX-2), annexin-1 (ANXA1), glucocorticoid receptor (GR), progesterone receptor (PR), and concentrations of prostaglandin F2α (PGF2α) and leukotrienes B4 (LTB4) and C4 (LTC4) in human endometrial explants.DesignEx vivo study.SettingUniversity hospital.Patient(s)Fifteen premenopausal patients undergoing surgery for benign gynecologic disorders.Intervention(s)Endometrial explants were obtained by aspiration curettage and stimulated ex vivo with interleukin-1β before exposure to CMA or DEX; mRNA levels were determined via reverse transcription–quantitative real-time polymerase chain reaction, and concentrations of arachidonic acid metabolites by enzyme immunoassays.Main Outcome Measure(s)Messenger RNA levels of COX-2, ANXA1, PR, and GR; concentrations of PGF2α, LTB4, and LTC4 in endometrial explants treated with CMA or DEX.Result(s)In IL-1β–treated explants COX-2 mRNA and PGF2α, concentrations were significantly down-regulated by CMA but not by DEX. Chlormadinone acetate did not affect mRNA abundance of ANXA1, PR, and GR.Conclusion(s)Our data suggest that CMA is a suppressor of COX-2 expression. Comparison with DEX revealed that progestin-specific activity of CMA may mainly be responsible for suppression of prostaglandin biosynthesis in human endometrium.