Abu Hashim Hatem, Ghayaty Essam, El Rakhawy Mohamed
Department of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Am J Obstet Gynecol. 2015 Oct;213(4):469-78. doi: 10.1016/j.ajog.2015.03.037. Epub 2015 Mar 19.
We sought to evaluate the therapeutic efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) with oral progestins for treatment of non-atypical endometrial hyperplasia (EH). Searches were conducted on PubMed, SCOPUS, and CENTRAL databases to August 2014, and reference lists of relevant articles were screened. The search was limited to articles conducted on human beings and females. The PRISMA Statement was followed. Seven randomized controlled trials (n = 766 women) were included. Main outcome measures were the therapeutic effect rate (histological response) after 3, 6, 12, and 24 months of treatment; rate of irregular vaginal bleeding; and the hysterectomy rate per woman randomized. The Cochrane Collaboration risk of bias tool was used for quality assessment. Metaanalysis was performed with fixed effects model. LNG-IUS achieved a highly significant therapeutic response rate compared with oral progestins after 3 months of treatment (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.39-3.82; P = .001, 5 trials, I(2) = 0%, n = 376), after 6 months of treatment (OR, 3.16; 95% CI, 1.84-5.45; P < .00001, 4 trials, I(2) = 0%, n = 397), after 12 months of treatment (OR, 5.73; 95% CI, 2.67-12.33; P < .00001, 2 trials, I(2) = 0%, n = 224), and after 24 months of treatment (OR, 7.46; 95% CI, 2.55-21.78; P = .0002, 1 trial, n = 104). Subgroup analysis showed evidence of highly significant therapeutic response following LNG-IUS compared with oral progestins for non-atypical simple as well as complex EH (OR, 2.51; 95% CI, 1.14-5.53; P = .02, 6 trials, I(2) = 0%, n = 290; and OR, 3.31; 95% CI, 1.62-6.74; P = .001, 4 trials, I(2) = 0%, n = 216, respectively). Compared with oral progestins, LNG-IUS achieved significantly fewer hysterectomies (OR, 0.26; 95% CI, 0.15-0.45; P < .00001, 3 trials, n = 362, I² = 42%). No difference was observed in the rate of irregular vaginal bleeding between both groups (OR, 1.12; 95% CI, 0.54-2.32; P = .76, 2 trials, n = 207, I² = 77%). Funnel plot analysis was not performed because of the relatively small number of included studies. For treatment of non-atypical EH, LNG-IUS achieves higher therapeutic effect rates and lower hysterectomy rates than oral progestins and should be offered as an alternative to oral progestins in these cases.
我们旨在评估左炔诺孕酮宫内缓释系统（LNG-IUS）联合口服孕激素治疗非典型子宫内膜增生（EH）的疗效。检索了截至2014年8月的PubMed、SCOPUS和CENTRAL数据库，并筛选了相关文章的参考文献列表。检索仅限于针对人类女性的文章。遵循PRISMA声明。纳入了7项随机对照试验（共766名女性）。主要结局指标为治疗3、6、12和24个月后的治疗有效率（组织学反应）；不规则阴道出血发生率；以及随机分组的每名女性的子宫切除率。使用Cochrane协作网偏倚风险工具进行质量评估。采用固定效应模型进行荟萃分析。治疗3个月后，与口服孕激素相比，LNG-IUS的治疗有效率显著更高（优势比[OR]为2.30；95%置信区间[CI]为1.39 - 3.82；P = 0.001，5项试验，I² = 0%，n = 376）；治疗6个月后（OR为3.16；95% CI为1.84 - 5.45；P < 0.00001，4项试验，I² = 0%，n = 397）；治疗12个月后（OR为5.73；95% CI为2.67 - 12.33；P < 0.00001，2项试验，I² = 0%，n = 224）；治疗24个月后（OR为7.46；95% CI为2.55 - 21.78；P = 0.0002，1项试验，n = 104）。亚组分析显示，与口服孕激素相比，LNG-IUS治疗非典型单纯性和复杂性EH后的治疗有效率显著更高（OR分别为2.51；95% CI为1.14 - 5.53；P = 0.02，6项试验，I² = 0%，n = 290；以及OR为3.31；95% CI为1.62 - 6.74；P = 0.001，4项试验，I² = 0%，n = 216）。与口服孕激素相比，LNG-IUS导致的子宫切除显著更少（OR为0.26；95% CI为0.15 - 0.45；P < 0.00001，3项试验，n = 362，I² = 42%）。两组间不规则阴道出血发生率无差异（OR为1.12；95% CI为（0.54 - 2.32；P = 0.76，2项试验，n = 207，I² = 77%）。由于纳入研究数量相对较少，未进行漏斗图分析。对于非典型EH的治疗，LNG-IUS比口服孕激素具有更高的治疗有效率和更低的子宫切除率，在这些情况下应作为口服孕激素的替代方案。
