title: Does dienogest influence the inflammatory response of endometriotic cells? A systematic review.
abstract: OBJECTIVE
  A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells.
  
  
  METHODS
  In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human).
  
  
  RESULTS
  After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear.
  
  
  CONCLUSIONS
  DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.|Department of Clinical Research, University of Berne, Murtenstrasse 35, 3010, Berne, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, 3010, Berne, Switzerland.|Department of Clinical Research, University of Berne, Murtenstrasse 35, 3010, Berne, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, 3010, Berne, Switzerland.|Department of Clinical Research, University of Berne, Murtenstrasse 35, 3010, Berne, Switzerland.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Bersinger
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Cagnacci
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.
authors.forename: Annibale
authors.initials: A
authors.lastname: Volpe
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, 3010, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch.|Department of Clinical Research, University of Berne, Murtenstrasse 35, 3010, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch.
authors.forename: Brett
authors.initials: B
authors.lastname: McKinnon
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D006727:Hormone Antagonists; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D011453:Prostaglandins; C023635:dienogest; D009277:Nandrolone
keywords: Chemokines; Cytokines; Dienogest; Endometriosis; Growth factors; Inflammation; Progestin; Progestogen; Prostaglandin