title: Dienogest reduces proliferation, aromatase expression and angiogenesis, and increases apoptosis in human endometriosis.
abstract: Dienogest is a novel progestin that is highly selective for progesterone receptors and inhibits endometriosis. However, it remains unknown how the administration of dienogest to patients with endometriosis impacts on their lesion tissues. The aim of this study was to evaluate the in vivo effect of dienogest on endometriosis tissue. We collected endometrioma tissues from patients treated with dienogest (N = 7) or not treated (N = 11, controls). Cell proliferation, aromatase expression and blood vessel density were evaluated by staining for Ki67, aromatase and the von Willebrand factor, respectively. Apoptosis was detected using the TUNEL assay. The proportion of Ki67 and aromatase positive epithelial cells was significantly lower in the dienogest group than in controls (p < 0.05, respectively). The number of TUNEL positive cells was significantly higher in the dienogest group (p < 0.05). The density of blood vessels in endometrioma was marginally lower in the dienogest group compared with controls (p = 0.20). Our study demonstrates that endometrioma taken from patients treated with dienogest show remarkable histological features such as reduction of proliferation, aromatase expression and angiogenesis, and increase of apoptosis. This study clarified the impact of dienogest on local histological events that explain its therapeutic effect on endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo , Tokyo , Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Miyashita
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Masashi
authors.initials: M
authors.lastname: Takamura
authors.forename: Gentaro
authors.initials: G
authors.lastname: Izumi
authors.forename: Miwako
authors.initials: M
authors.lastname: Nagai
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D004715:Endometriosis / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D014841:von Willebrand Factor
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D014841:von Willebrand Factor; C023635:dienogest; D009277:Nandrolone; D001141:Aromatase
keywords: Apoptosis; aromatase; dienogest; endometriosis; proliferation