Treatment with Bazedoxifene and Conjugated Estrogens Results in Regression of Endometriosis in a Murine Model1

Hanyia Naqvi, Sharif Sakr, Thomas Presti, Graciela Krikun, Barry S. Komm, Barry Komm, Hugh S Taylor
Biology of reproduction · 2014 · vol. 90(6) , pp. 121 · doi:10.1095/biolreprod.113.114165 · PMID:24740602 · PMC4093999 · W2052516455
article OA: bronze CC0 ⤵ 34 in-corpus citations
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Treatment with bazedoxifene alone or combined with conjugated estrogens reduced endometriotic lesion size in a murine model and decreased estrogen receptor expression.

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Estrogens, Conjugated (USP) Indoles Selective Estrogen Receptor Modulators Animals Cell Proliferation Cell Proliferation Disease Models, Animal Endometriosis Endometriosis Estrogen Receptor alpha Estrogen Receptor alpha Estrogen Receptor alpha Estrogens, Conjugated (USP) Female Humans Indoles Mice, Inbred Strains Organ Size Organ Size

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