Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic stromal cells in spheroid culture

Objective: To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E-2 (PGE(2)) in human endometriotic stromal cells (ESCs). Design: Experimental study in vitro. Setting: University hospital. Patient(s): Seventeen patients with ovarian endometrioma. Intervention(s): ESCs from chocolate cyst linings of ovaries were treated with DNG. Main Outcome Measure(s): Expression of aromatase and COX-2 evaluated in spheroid cultures of human ESCs by real-time quantitative polymerase chain-reaction and immunocytochemistry, production of PGE(2) quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-kappa B) DNA-binding examined by ELISA and immunocytochemistry. Result(s): The pharmaceutical actions of DNG on the expression of aromatase and COX-2 and the production of PGE(2) were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE(2) were expressed in spheroid cultures than in conventional ESCs monolayers. In the spheroid cultures, DNG (10(-7) M) and progesterone (10(-7) M) inhibited the expression of aromatase, COX-2, and PGE(2). DNG also inhibited NF-kappa B DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-kappa B p50 nuclear localization. Conclusion(s): Because DNG inhibits aromatase and COX-2 expression as well as PGE(2) production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis. (Fertil Steril(R) 2012;97:477-82. (C) 2012 by American Society for Reproductive Medicine.)