Chlormadinone acetate suppresses prostaglandin biosynthesis in human endometrial explants

Objective: To 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 F-2 alpha (PGF(2 alpha)) and leukotrienes B-4 (LTB4) and C-4 (LTC4) in human endometrial explants. Design: Ex vivo study. Setting: University 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-1 beta 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 PGF(2 alpha), LTB4, and LTC4 in endometrial explants treated with CMA or DEX. Result(s): In IL-1 beta-treated explants COX-2 mRNA and PGF(2 alpha), 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. (Fertil Steril (R) 2012;98:1017-22. (C)2012 by American Society for Reproductive Medicine.)