摘要
目的总结国内外对他莫昔芬的药理机制及其对卵巢功能影响的相关研究,为临床中对乳腺癌患者治疗方案的选择提供资料及依据。方法检索Med Line、OVID、CBM、CNKI等数据库,以"他莫昔芬、药理机制、卵巢、性激素"等为关键词,检索1950年1月至2014年1月期间的相关文献,共检索到英文文献1 286条,中文文献621条。纳入标准:1他莫昔芬在体内的代谢、他莫昔芬的代谢效应与CYP2D6基因多态性的相关临床及基础研究;2雌激素受体、共同调节蛋白在他莫昔芬发挥效应时所起的作用;3他莫昔芬诱导排卵、引起子宫内膜增厚、性激素水平改变的相关临床及基础研究。符合纳入标准文献共152篇,最后77篇文献纳入本综述分析。结果 1他莫昔芬代谢产物4-羟基-N-去甲他莫昔芬是其发挥作用的主要成分,其浓度降低可预示预后不良;2 CYP2D6的基因多态性会影响他莫昔芬的代谢效应,影响对乳腺癌患者的治疗效果;3他莫昔芬发挥效应需要雌激素受体及共同调节蛋白的共同参与;4他莫昔芬可作用于下丘脑-垂体-卵巢轴及卵巢、子宫内膜的雌激素受体,影响生殖系统功能。结论他莫昔芬的代谢效应受基因调节,其可通过雌激素受体影响生殖系统功能。他莫昔芬影响性激素水平的机制及乳腺癌术后口服他莫昔芬的患者持续监测性激素水平是否能够反映卵巢功能,尚需进一步研究。
Objective To summarize the relevant studies of pharmacological mechanism of tamoxifen and its influence on ovary function in order to provide information and evidence for the therapy of breast cancer.Methods Papers published from January 1950 to January 2014,were retrieved in MedLine,OVID,CBM,CNKI databases using the keywords on tamoxifen,drug metabolism,ovary,sex hormone,etc,1 286 papers were retrieved in English literatures,and621 in Chinese literatures.Criteria of paper adoption：① The clinical and basic studies about metabolism of tamoxifen,metabolic effect of tamoxifen,and gene polymorphism of CYP2D6.② The role played by estrogen receptor and protein cofactors in tamoxifen effect.③ The clinical and basic studies about tamoxifen induced ovulation,caused endometrial thickening,changed sex hormone levels.According to the above criteria,152 papers were selected,and 77 papers out of them were finally analyzed and reviewed.Results ① The tamoxifen metabolite 4-OH-N-tamoxifen was the main working component,the decreased levels could predict the poor prognosis.② The CYP2D6 gene polymorphism could affect the metabolic effect of tamoxifen and the therapeutic effect of patients with breast cancer.③ The metabolic effect of tamoxifen needed the participation of the estrogen receptors and protein cofactors.④ Tamoxifen could affect the reproductive system function through the estrogen receptor of H-P-O axis,ovary,and endometrium.Conclusions Metabolic effect of tamoxifen is regulated by gene,it could affect reproductive system functions through estrogen receptor.The mechanism that tamoxifen cowld affect the hormone levels and wherther it could reflect the ovarian function by monitering the hormone levels continuously for patients with breast cancer need to be researched.
出处
《中国普外基础与临床杂志》
CAS
2015年第11期1397-1404,共8页
Chinese Journal of Bases and Clinics In General Surgery
