title: The estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibit endometriotic cell proliferation in estrogen-receptor-independent manner.
abstract: Endometriosis, a painful disorder associated with infertility, is estimated to occur in approximately 7-10% of reproductive age women. Although endometriosis is considered as an estrogen-dependent disease, the role of estrogen metabolites via receptor-independent mechanisms has not yet been comprehensively clarified. In the present study, growth studies were performed comparing the effect of estradiol (E2), estrogen metabolites, that is, 2-hydroxyestradiol (2-OHE2) and 2-methoxyestradiol (2-ME), as well as estrogen-receptor-independent mechanisms using the estrogen receptor antagonist fulvestrant, on cell proliferation of endometriotic cells. The estrogen metabolites 2-OHE2 and 2-ME inhibited cell growth in a dose-dependent manner in pharmacological doses. Lower concentrations of 2-OHE2 had a stimulating effect on cell proliferation while pharmacologic doses exerted an antimitogenic effect. The effects on cell growth were at least partially receptor-independent, as demonstrated by simultaneous receptor antagonization with fulvestrant. In conclusion, our results demonstrate that in pharmacological doses the estrogen metabolites 2-ME and 2-OHE2 show inhibiting effects on the proliferation of endometriotic cells and may be promising substances for the treatment of endometriosis.
authors.affiliation: a Division of Gynecology , University Hospital of Zurich , Zurich , Switzerland and.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Samartzis
authors.affiliation: a Division of Gynecology , University Hospital of Zurich , Zurich , Switzerland and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Imesch
authors.affiliation: b Clinic for Reproductive Endocrinology, University Hospital of Zurich , Zurich , Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Twiehaus
authors.affiliation: b Clinic for Reproductive Endocrinology, University Hospital of Zurich , Zurich , Switzerland.
authors.forename: Raghvendra K
authors.initials: RK
authors.lastname: Dubey
authors.affiliation: b Clinic for Reproductive Endocrinology, University Hospital of Zurich , Zurich , Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Leeners
mesh_terms: D000077584:2-Methoxyestradiol; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000188:drug therapy*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans
chemical_list: D065171:Estrogen Receptor Antagonists; D000077267:Fulvestrant; D004958:Estradiol; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol
keywords: 2-hydroxyestradiol; 2-methoxyestradiol; Endometriosis; estrogen metabolites; fulvestrant (ICI 182780)