Naqvi Hanyia, Sakr Sharif, Presti Thomas, Krikun Graciela, Komm Barry, Taylor Hugh S
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Pfizer, Collegeville, Pennsylvania.
Biol Reprod. 2014 Jun;90(6):121. doi: 10.1095/biolreprod.113.114165. Epub 2014 Apr 16.
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.
巴多昔芬（BZA）是一种选择性雌激素受体调节剂（SERM），可抑制雌激素对子宫内膜增殖的作用。在此，我们评估了一种包含BZA和共轭雌激素（CE）的组织选择性雌激素复合物（TSEC）对子宫内膜异位症小鼠模型中异位子宫内膜病变的影响。在60只雌性CD-1小鼠中建立了实验性子宫内膜异位症模型。将小鼠随机分为10组，分别接受不同剂量的BZA（1、2、3或5 mg/kg/天）、BZA（1、2、3或5 mg/kg/天）与CE（3 mg/kg/天）联合使用、单独使用CE治疗（3 mg/kg/天）或赋形剂对照，持续8周。与对照组相比，单独使用BZA或含BZA/CE的TSEC治疗可使子宫内膜异位症病变大小减小。未治疗病变的平均表面积为19.6平方毫米。用BZA或BZA/CE治疗可使病变大小减小（分别降至8.8和7.8平方毫米）。BZA和BZA/CE治疗组之间或两种治疗的不同剂量之间，病变大小均未发现显著差异。治疗组中未观察到卵巢囊肿形成。与对照治疗相比，含较高BZA剂量（3和5 mg/kg/天）的TSEC治疗导致雌激素受体（Esr1）mRNA表达水平显著降低。孕酮受体（Pgr）的表达未观察到差异。免疫组织化学分析也显示ESR蛋白减少。CE和BZA的联合使用可能被证明是子宫内膜异位症的一种新的治疗选择。
