Subakir S B, Setiadi E, Affandi B, Pringgoutomo S, Freisleben H J
Faculty of Medicine, University of Indonesia, Salemba Raya No. 4, Jakarta 10430, Indonesia.
Toxicology. 2000 Aug 7;148(2-3):173-8. doi: 10.1016/s0300-483x(00)00208-0.
Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle. This disturbance in the angiogenic process may be caused by an imbalance of pro- and antioxidant processes in the endometrium of Norplant users. The aim of this study is to investigate the effect of vitamin E on the endometrial angiogenic activity and to assess the efficacy of vitamin E supplementation in treating endometrial bleeding in Norplant users. Subjects for this study were selected from Norplant users with an exposure of at least 3 months, with endometrial bleeding and recruited on the basis of fully informed consent. TBA reaction was used to measure degradation products of lipid peroxidation. The endometrial angiogenic response was assayed according to Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from endometrial biopsies were incubated in vitro with vitamin E or placebo before angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or placebo for 10 days/month were given to the subjects with double blind randomisation. The results showed that the blood levels of TBA-reactive substances were significantly higher in Norplant users than in controls. In the endometrium from Norplant users with bleeding problems, in vitro supplementation of vitamin E resulted in a significantly higher angiogenic score than placebo. Although a highly significant reduction of bleeding days in both groups, vitamin E and placebo, was seen during the 2 months of the study, the number of bleeding days was significantly lower in women treated with vitamin E than with placebo.
皮下埋植左炔诺孕酮是印度尼西亚使用的一种避孕方法。子宫内膜出血是停止使用左炔诺孕酮的一个主要原因。研究发现，使用左炔诺孕酮的女性子宫内膜中的血管生成反应低于月经周期正常的女性。左炔诺孕酮使用者子宫内膜血管生成过程的这种紊乱可能是由于其子宫内膜中促氧化和抗氧化过程失衡所致。本研究的目的是探讨维生素E对子宫内膜血管生成活性的影响，并评估补充维生素E治疗左炔诺孕酮使用者子宫内膜出血的疗效。本研究的受试者选自至少暴露3个月、有子宫内膜出血且在充分知情同意的基础上招募的左炔诺孕酮使用者。采用硫代巴比妥酸反应法测定脂质过氧化降解产物。根据福克曼等人的方法测定子宫内膜血管生成反应（Folkman et al., 1989. Nature 239, 58 - 61）。在进行血管生成测量之前，将子宫内膜活检样本在体外与维生素E或安慰剂一起孵育。对于体内补充，以双盲随机的方式给予受试者每天200毫克维生素E或每月10天的安慰剂。结果显示，左炔诺孕酮使用者的硫代巴比妥酸反应性物质的血液水平显著高于对照组。在有出血问题的左炔诺孕酮使用者的子宫内膜中，体外补充维生素E导致血管生成评分显著高于安慰剂。尽管在研究的2个月期间，维生素E组和安慰剂组的出血天数均显著减少，但维生素E治疗的女性的出血天数显著低于安慰剂组。
