Morales-Prieto Diana M, Herrmann Joerg, Osterwald Hermann, Kochhar Prithi S, Schleussner Ekkehard, Markert Udo R, Oettel Michael
Placenta-Labor, Klinik für Geburtsmedizin, Universitätsklinikum Jena, Jena, Germany.
Klinik für Gynäkologie und Geburtshilfe, Sophien- und Hufeland-Klinikum, Weimar, Germany.
Reprod Biol. 2018 Sep;18(3):252-258. doi: 10.1016/j.repbio.2018.07.002. Epub 2018 Jul 9.
Dienogest (DNG) administration is a well-established treatment for endometriosis but bleeding irregularities remain its main disadvantage. Changes in diet, mainly to vegetable consumption, are beneficial in the treatment of estrogen-related pathologies but their use for endometriosis has been poorly studied. In this study, addition of the phytochemical 3,3'-diindolylmethane (DIM) to DNG therapy has been investigated in in vitro and ex vivo models for endometriosis and in a small cohort of women with endometriosis. Endometrial Ishikawa cells were treated with DNG or DIM at dosages from 10 M to 10 M for up to 72 h. Cell proliferation was measured by assessing BrdU incorporation. Endometrial tissue from women with endometriosis and controls was incubated with DNG or a combination of DNG and DIM. Tissue viability was determined using a modified colorimetric MTS assay. 17β-estradiol secretion was quantified by an electro-chemiluminescence immunoassay. Finally, DNG as monotherapy or in combination with DIM was randomly administered to women with endometriosis (n = 8) over 3 months. Bleeding patterns and associated pelvic pain were assessed by Visual Analogue Scale (VAS). DNG and DIM significantly reduced cell proliferation in Ishikawa cells. Ex vivo, DIM reduced viability and estradiol secretion specifically in endometriotic but not in normal endometrial tissue. This effect was enhanced by combination with DNG. Endometriosis associated pelvic pain was significantly reduced in patients taking the DNG-DIM combination therapy compared to those taking DNG alone. Bleeding pattern (number and duration of episodes) was significantly improved by addition of DIM to the DNG treatment. In conclusion, addition of DIM enhances effects of DNG ex vivo and may ameliorate bleeding patterns in endometriosis patients.
地诺孕素（DNG）给药是一种成熟的子宫内膜异位症治疗方法，但出血不规律仍是其主要缺点。饮食改变，主要是增加蔬菜摄入量，对雌激素相关疾病的治疗有益，但在子宫内膜异位症治疗中的应用研究较少。在本研究中，已在子宫内膜异位症的体外和离体模型以及一小群子宫内膜异位症女性中研究了将植物化学物质3,3'-二吲哚甲烷（DIM）添加到DNG治疗中的效果。用10 nM至10 μM剂量的DNG或DIM处理子宫内膜 Ishikawa 细胞长达72小时。通过评估溴脱氧尿苷（BrdU）掺入来测量细胞增殖。将子宫内膜异位症女性和对照组的子宫内膜组织与DNG或DNG与DIM的组合一起孵育。使用改良的比色MTS测定法测定组织活力。通过电化学发光免疫测定法定量17β-雌二醇分泌。最后，将DNG单药治疗或与DIM联合治疗随机给予子宫内膜异位症女性（n = 8），持续3个月。通过视觉模拟量表（VAS）评估出血模式和相关的盆腔疼痛。DNG和DIM显著降低了Ishikawa细胞中的细胞增殖。在体外，DIM特异性降低了子宫内膜异位组织而非正常子宫内膜组织的活力和雌二醇分泌。与DNG联合使用可增强这种效果。与单独服用DNG的患者相比，服用DNG-DIM联合治疗的患者中与子宫内膜异位症相关的盆腔疼痛显著减轻。在DNG治疗中添加DIM可显著改善出血模式（发作次数和持续时间）。总之，添加DIM可增强DNG在体外的作用，并可能改善子宫内膜异位症患者的出血模式。
