title: Treatment with bazedoxifene and conjugated estrogens results in regression of endometriosis in a murine model.
abstract: Bazedoxifene (BZA), a selective estrogen receptor modulator (SERM), inhibits the action of estrogens on endometrial proliferation. Here, we evaluate the effect of a tissue-selective estrogen complex (TSEC) containing BZA and conjugated estrogens (CE) on ectopic endometrial lesions in a mouse model of endometriosis. Experimental endometriosis was created in 60 female CD-1 mice. The mice were randomly divided into 10 groups that received varying doses of either BZA (1, 2, 3, or 5 mg/kg/day), BZA (1, 2, 3, or 5 mg/kg/day) in combination with CE (3 mg/kg/day), CE treatment alone (3 mg/kg/day), or vehicle control for 8 wk. Treatment with BZA alone or the TSEC containing BZA/CE led to a decrease in endometriotic lesion size compared to controls. The mean surface area of the untreated lesions was 19.6 mm(2). Treatment with BZA or BZA/CE resulted in reduced lesion size (to 8.8 and 7.8 mm(2), respectively). No significant difference was found in lesion size between the BZA and BZA/CE treatment groups or between different doses of either treatment. Ovarian cyst formation was not evident in the treated groups. Treatment with the TSEC containing higher BZA dosages (3 and 5 mg/kg/day) led to significantly lower levels of estrogen receptor (Esr1) mRNA expression compared to the control treatment. No differences were observed in expression of progesterone receptor (Pgr). Immunohistochemical analysis also demonstrated a decrease in ESR protein. The combination of CE and BZA may prove to be a novel treatment option for endometriosis.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Hanyia
authors.initials: H
authors.lastname: Naqvi
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Sharif
authors.initials: S
authors.lastname: Sakr
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Thomas
authors.initials: T
authors.lastname: Presti
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.affiliation: Pfizer, Collegeville, Pennsylvania.
authors.forename: Barry
authors.initials: B
authors.lastname: Komm
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut hugh.taylor@yale.edu.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D047628:Estrogen Receptor alpha; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: bazedoxifene (BZA); conjugated estrogen (CE); endometriosis; hormone receptors; tissue-specific estrogen complex (TSEC)
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