子宫内膜癌是世界上最常见的妇科恶性肿瘤,发展到子宫内膜增生的初级阶段。不典型的子宫内膜增生提示明显的癌前状态,伴有明显的子宫内膜癌进展,往往发生在年轻的时候。口服孕激素已被用作不典型子宫内膜增生的年轻女性的保守治疗,但其耐受性差,副作用可能会限制其整体疗效.因此,与目前可用的选择相比,找到一种具有更好耐受性和更少副作用的安全有效的保留生育的治疗方法变得越来越重要和必要。左炔诺孕酮宫内释放系统(LNG-IUS)已用于为接受他莫昔芬辅助治疗的乳腺癌妇女提供子宫内膜保护。左炔诺孕酮的抗增殖功能被认为可以降低子宫内膜增生的风险。
确定口服和宫内孕激素治疗非典型子宫内膜增生的疗效和安全性。
2018年7月,我们搜索了CENTRAL;MEDLINE;Embase;CINAHL,PsycINFO和中国国家知识基础设施相关试验。2018年11月搜索了Cochrane妇科和生育(CGF)专业登记册和Embase。我们试图从已发表研究的参考文献中确定试验。我们还在五个主要的临床试验注册中心搜索了正在进行的试验。
经组织学确诊的单纯性或复杂性子宫内膜增生伴异型的女性患者口服和宫内孕激素(LNG-IUS)与其他或安慰剂的随机对照试验(RCT)。
两位综述作者评估了试验资格和偏倚风险,并提取了数据。审查的主要结果是消退率和不良反应。次要结果包括复发率和接受子宫切除术的妇女比例。我们使用等级方法来判断证据的质量。
我们纳入了一项RCT(153名女性),比较了每天服用20微克(μu)左炔诺孕酮与10毫克连续或周期性口服甲羟孕酮(MPA)治疗任何类型子宫内膜增生的LNG-IUS。在这项研究中,只有19名女性在治疗前经组织学证实患有非典型复杂增生。证据质量低或非常低。纳入研究的偏倚风险较低,但是证据的质量受到不精确和间接性的严重限制。在非典型子宫内膜增生的女性中,我们没有发现任何比较LNG-IUS或口服孕激素与安慰剂的RCTS。在19例非典型复杂增生的女性中,治疗六个月后,没有足够的证据来确定LNG-IUS组和孕酮组之间的回归率是否存在差异(比值比(OR)2.76,95%置信区间(CI)0.26至29.73;1RCT亚组,19个女人,非常低质量的证据)。LNG-IUS组的消退率为100%(n=6/6),孕酮组的消退率为77%(n=10/13)。在总研究人群中(N=153),在6个月的治疗中,主要的不良反应是恶心和阴道出血。没有证据表明两组之间的恶心发生率存在差异(OR0.58,95%CI0.28至1.18;1RCT,153名妇女,非常低质量的证据)。阴道出血在LNG-IUS组中更为常见(OR2.89,95%CI1.11~7.52;1个RCT,153名妇女,低质量证据)。除了恶心和阴道出血,未报告其他不良反应.
我们没有发现不典型子宫内膜增生女性的RCTS,我们的发现来自一个更大的RCT中19名女性的亚组。所有使用LNG-IUS系统的6名女性均实现了非典型增生的消退,但没有足够的证据就LNG-IUS与口服孕酮(MPA)在这组女性中的相对疗效得出任何结论.当在患有任何类型子宫内膜增生的女性人群中进行评估时,没有明确的证据表明LNG-IUS和口服孕酮(MPA)在恶心风险方面存在差异,但使用LNG-IUS的女性更有可能发生阴道出血.需要更大规模的研究来评估口服和宫内孕激素治疗非典型子宫内膜增生的疗效和安全性。
Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia.
To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the
China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries.
Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia.
Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence.
We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral
medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia.Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13).Among the total study population (N = 153), over the six months\' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported.
We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.