Lethaby Anne, Hussain Munawar, Rishworth Josephine R, Rees Margaret C
Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland, New Zealand, 1142.
Cochrane Database Syst Rev. 2015 Apr 30(4):CD002126. doi: 10.1002/14651858.CD002126.pub3.
Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. However, women may complain of excessive bleeding when their blood loss is less than 80 mL. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative.The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss. Case studies of two types of progesterone or progestogen-releasing systems, Progestasert and Mirena, reported reductions of up to 90% and improvements in dysmenorrhoea (pain or cramps during menstruation). Insertion, however, may be regarded as invasive by some women, which affects its acceptability as a treatment. Frequent intermenstrual bleeding and spotting is also likely during the first few months after commencing treatment.
To determine the effectiveness, acceptability and safety of progesterone or progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding.
All randomised controlled trials of progesterone or progestogen-releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of The Cochrane Library, the specialised register of MDSG, MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (inception to December 2014) and PsycINFO (inception to January 2015). Additional searches were undertaken for grey literature and for unpublished trials in trial registers. Companies producing progestogen-releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials.
Randomised controlled trials in women of reproductive age treated with progesterone or progestogen-releasing intrauterine devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding within primary care, family planning or specialist clinic settings were eligible for inclusion. Women with postmenopausal bleeding, intermenstrual or irregular bleeding, or pathological causes of heavy menstrual bleeding were excluded.
Potential trials were independently assessed by at least two review authors. The review authors extracted the data independently and data were pooled where appropriate. Risk ratios (RRs) were estimated from the data for dichotomous outcomes and mean differences (MD) for continuous outcomes. The primary outcomes were reduction in menstrual blood loss and satisfaction; in addition, rate of adverse effects, changes in quality of life, failure of treatment and withdrawal from treatment were also assessed.
We included 21 RCTs (2082 women). The included trials mostly assessed the levonorgestrel-releasing intrauterine device (LNG IUS) (no conclusions could be reached from one small study assessing Progestasert which was discontinued in 2001) and so conclusions are based only on LNG IUS. Comparisons were made with placebo, oral medical treatment, endometrial destruction techniques and hysterectomy. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency.Seven studies compared the LNG IUS with oral medical therapy: either norethisterone acetate (NET) administered over most of the menstrual cycle, medroxyprogesterone acetate (MPA) (administered for 10 days), the oral contraceptive pill, mefenamic acid or usual medical treatment where participants could choose the oral treatment that was most suitable. The LNG IUS was more effective at reducing HMB as measured by the alkaline haematin method (MD 66.91 mL, 95% CI 42.61 to 91.20; two studies, 170 women; I(2) = 81%, low quality evidence) or by Pictorial Bleeding Assessment Chart (PBAC) scores (MD 55.05, 95% CI 27.83 to 82.28; three studies, 335 women; I(2) = 79%, low quality evidence), improving quality of life and a greater number of women continued with their treatment at two years when compared with oral treatment. Although substantial heterogeneity was identified for the bleeding outcomes, the direction of effect consistently favoured the LNG IUS. There was insufficient evidence to reach conclusions on satisfaction. Minor adverse effects (such as pelvic pain, breast tenderness and ovarian cysts) were more common with the LNG IUS.Ten studies compared the LNG IUS with endometrial destruction techniques: three with transcervical resection, one with rollerball ablation and six with thermal balloon ablation. Evidence was inconsistent and very low quality with respect to reduction in bleeding outcomes and satisfaction was comparable between treatments (low and moderate quality evidence). Improvements in quality of life were experienced with both types of treatment. Minor adverse events were more common with the LNG IUS overall, but it appeared more cost effective compared to thermal ablation within a two-year time frame in one study.Three studies compared the LNG IUS with hysterectomy. The LNG IUS was not as successful at reducing HMB as hysterectomy (high quality evidence). The women in these studies reported improved quality of life, regardless of treatment. In spite of the high rate of surgical treatment in those having LNG IUS within 10 years, the LNG IUS was more cost effective than hysterectomy.
AUTHORS' CONCLUSIONS: The levonorgestrel-releasing intrauterine device (LNG IUS) is more effective than oral medication as a treatment for heavy menstrual bleeding (HMB). It is associated with a greater reduction in HMB, improved quality of life and appears to be more acceptable long term but is associated with more minor adverse effects than oral therapy.When compared to endometrial ablation, it is not clear whether the LNG IUS offers any benefits with regard to reduced HMB and satisfaction rates and quality of life measures were similar. Some minor adverse effects were more common with the LNG IUS but it appeared to be more cost effective than endometrial ablation techniques.The LNG IUS was less effective than hysterectomy in reducing HMB. Both treatments improved quality of life but the LNG IUS appeared more cost effective than hysterectomy for up to 10 years after treatment.
月经过多（HMB）是女性健康问题的一个重要原因，在英国，它占所有妇科转诊病例的12%。临床上，月经过多被定义为每个月经周期失血大于或等于80毫升。然而，当女性失血量少于80毫升时，她们也可能会抱怨出血过多。子宫切除术常被用于治疗有此症状的女性，但药物治疗可能是一种成功的替代方法。宫内节育器最初是作为一种避孕工具开发的，但在这些装置中添加孕激素后，月经失血量大幅减少。两种孕激素或孕激素释放系统（普维拉和曼月乐）的案例研究报告称，月经失血量减少了90%，痛经（月经期间的疼痛或痉挛）也有所改善。然而，对一些女性来说，放置宫内节育器可能被视为一种侵入性操作，这影响了它作为一种治疗方法的可接受性。在开始治疗后的最初几个月里，也可能会频繁出现经间期出血和点滴出血。
确定孕激素或孕激素释放宫内节育器在减少月经过多方面的有效性、可接受性和安全性。
通过电子检索Cochrane图书馆、MDSG专业注册库、MEDLINE（1966年至2015年1月）、EMBASE（1980年至2015年1月）、CINAHL（创刊至2014年12月）和PsycINFO（创刊至2015年1月），获得了所有关于孕激素或孕激素释放宫内节育器治疗月经过多的随机对照试验。还对灰色文献和试验注册库中的未发表试验进行了额外检索。联系了生产孕激素释放宫内节育器的公司和该领域的专家，以获取已发表和未发表试验的信息。
在初级保健、计划生育或专科诊所环境中，对使用孕激素或孕激素释放宫内节育器治疗月经过多的育龄妇女进行的随机对照试验，与不治疗、安慰剂或其他药物或手术治疗进行比较的试验符合纳入标准。排除绝经后出血、经间期或不规则出血或月经过多的病理原因的女性。
潜在试验至少由两名综述作者独立评估。综述作者独立提取数据，并在适当情况下进行数据合并。从二分结果的数据中估计风险比（RRs），从连续结果的数据中估计平均差（MD）。主要结果是月经失血量的减少和满意度；此外，还评估了不良反应发生率、生活质量变化、治疗失败和退出治疗情况。
我们纳入了21项随机对照试验（2082名女性）。纳入的试验大多评估了左炔诺孕酮宫内节育系统（LNG IUS）（一项评估普维拉的小型研究未得出结论，该研究于2001年停止），因此结论仅基于LNG IUS。与安慰剂、口服药物治疗、子宫内膜破坏技术和子宫切除术进行了比较。每次比较的证据总体质量评级从极低到高不等。证据的局限性包括研究方法报告不充分和不一致。七项研究将LNG IUS与口服药物治疗进行了比较：在大部分月经周期使用醋酸炔诺酮（NET）、醋酸甲羟孕酮（MPA）（使用10天）、口服避孕药、甲芬那酸或常规药物治疗，参与者可以选择最适合的口服治疗。通过碱性高铁血红素法测量，LNG IUS在减少月经过多方面更有效（MD 66.91毫升，95%CI 42.61至91.20；两项研究，170名女性；I(2)=81%，低质量证据），或通过图片出血评估图（PBAC）评分（MD 55.05，95%CI 27.83至82.28；三项研究，335名女性；I(2)=79%，低质量证据），改善了生活质量，与口服治疗相比，两年时继续接受治疗的女性更多。尽管在出血结果方面发现了大量异质性，但效果方向始终有利于LNG IUS。没有足够的证据得出关于满意度的结论。LNG IUS的轻微不良反应（如盆腔疼痛、乳房压痛和卵巢囊肿）更常见。十项研究将LNG IUS与子宫内膜破坏技术进行了比较：三项与经宫颈切除术、一项与滚球消融术、六项与热球囊消融术。关于出血结果的减少，证据不一致且质量极低，治疗之间的满意度相当（低和中等质量证据）。两种治疗都改善了生活质量。总体而言，LNG IUS的轻微不良事件更常见，但在一项研究中，与热消融术相比，在两年时间内它似乎更具成本效益。三项研究将LNG IUS与子宫切除术进行了比较。LNG IUS在减少月经过多方面不如子宫切除术成功（高质量证据）。这些研究中的女性报告生活质量有所改善，无论接受何种治疗。尽管在10年内接受LNG IUS治疗的患者手术治疗率较高，但LNG IUS比子宫切除术更具成本效益。
左炔诺孕酮宫内节育系统（LNG IUS）作为月经过多（HMB）的治疗方法比口服药物更有效。它与月经过多减少幅度更大、生活质量改善有关，似乎长期更易被接受，但与口服治疗相比，不良反应更多。与子宫内膜消融术相比，不清楚LNG IUS在减少月经过多方面是否具有任何优势，满意度和生活质量指标相似。LNG IUS的一些轻微不良反应更常见，但与子宫内膜消融技术相比，它似乎更具成本效益。LNG IUS在减少月经过多方面不如子宫切除术有效。两种治疗都改善了生活质量，但LNG IUS在治疗后长达10年的时间里似乎比子宫切除术更具成本效益。
