Mueck A O, Seeger H, Lippert T H
Universitäts-Frauenklinik, Tübingen, Germany.
Zentralbl Gynakol. 2003 Nov;125(11):458-66. doi: 10.1055/s-2003-44575.
Estradiol can be metabolized to substances eliciting different, partly opposite effects even at low concentrations as shown in own investigations, e. g., regarding (anti)angiogenic actions. Specific anticancerogenic effects are ascribed to 2-hydroxyestrone and particularly 2-methoxyestradiol. In contrast, 16alpha-hydroxyestrone and the 4-hydroxyestrogens may be genotoxic under certain circumstances. Furthermore there are indications that endogenous production of proliferation-stimulating metabolites is raised in some cancers. Especially the urinary excretion of 2-hydroxyestrone to 16alpha-hydroxyestrone was investigated showing in own and other clinical studies a lower ratio in postmenopausal women with breast cancer. Research is ongoing inasfar the determination of estradiol metabolites also in blood or directly in the breast tissue by means of sensitive laboratory methods may allow predictive statements. However, it has be to consider that estradiol metabolism can be influenced by external factors such as nutrition, smoking, sports and drugs such as L-thyroxine and H2-antagonists. We were able to demonstrate that estradiol metabolism during estradiol treatment depends on the application mode and might be differently influenced by addition of the various progestins. Whether the investigation of gene polymorphism of enzymes, which are involved in estradiol metabolism, may be helpful for the assessment or treatment of risk patients, to our opinion needs further research.
正如我们自己的研究所表明的，即使在低浓度下，雌二醇也可代谢为具有不同甚至部分相反作用的物质，例如在（抗）血管生成作用方面。特定的抗癌作用归因于2-羟雌酮，特别是2-甲氧基雌二醇。相比之下，16α-羟雌酮和4-羟基雌激素在某些情况下可能具有基因毒性。此外，有迹象表明，某些癌症中增殖刺激代谢物的内源性产生会增加。特别是对2-羟雌酮与16α-羟雌酮的尿排泄进行了研究，我们自己的研究和其他临床研究表明，绝经后乳腺癌妇女的这一比值较低。目前正在进行研究，因为通过灵敏的实验室方法测定血液或直接在乳腺组织中的雌二醇代谢物可能有助于做出预测性判断。然而，必须考虑到，雌二醇代谢会受到外部因素的影响，如营养、吸烟、运动以及L-甲状腺素和H2拮抗剂等药物。我们能够证明，雌二醇治疗期间的雌二醇代谢取决于应用方式，并且可能会受到各种孕激素添加的不同影响。就我们看来，参与雌二醇代谢的酶的基因多态性研究是否有助于评估或治疗高危患者，还需要进一步研究。
