孕激素受体调节剂治疗子宫内膜异位症。
完整摘要 · 中文译文
理由：子宫内膜异位症被定义为子宫腔外出现子宫内膜样组织。该疾病为雌激素依赖性，因此主要见于育龄期。由于其对于宫内膜具有抗增殖作用，孕激素受体调节剂（PRMs）已被提倡用于治疗子宫内膜异位症。这是对先前于2017年发表的Cochrane系统评价的更新。 目的：评估孕激素受体调节剂（PRMs）在治疗子宫内膜异位症中的有效性和安全性。 检索方法：为识别研究，我们检索了在线资源，包括Cochrane妇科与生育（CGF）组试验注册库、CENTRAL、MEDLINE、Embase、PsycINFO、ClinicalTrials.gov以及世界卫生组织（WHO）试验注册平台，检索截止至2026年4月16日。我们还检查了参考文献列表，并联系了研究作者和专家。 纳入标准：我们纳入了随机对照试验（RCT），比较PRMs与安慰剂、不治疗或其他药物治疗在有症状的子宫内膜异位症女性中的效果。 结局指标：我们的关键结局指标为总体疼痛；最令人困扰症状（包括痛经和性交痛）的改善；以及PRM干预导致的不良事件。我们的重要结局指标包括生活质量（QoL）和患者对治疗的满意度。 偏倚风险：我们使用Cochrane的RoB 2工具来评估本系统评价结局中的偏倚风险。 综合方法：两名综述作者独立根据纳入标准评估研究、提取数据并评估偏倚风险，必要时咨询第三名综述作者。我们使用Mantel-Haenszel比值比（ORs）、95%置信区间（CIs）和固定效应模型分析二分类结局。我们使用组间均数差（MD）分析连续结局，并呈现95%置信区间。我们采用GRADE方法评估证据的确定性为高、中、低或极低。 纳入研究：本次更新中没有新的研究符合纳入标准。在已纳入综述的九项研究（922名女性）中，两项比较了米非司酮与安慰剂或比较了不同剂量的米非司酮，四项比较了孕三烯酮与达那唑、孕三烯酮与促性腺激素释放激素（GnRH）类似物，或比较了不同剂量的孕三烯酮。一项研究比较了阿索普瑞尼尔（asoprisnil）与安慰剂。该阿索普瑞尼尔研究未提供可提取的数值数据，仅被纳入叙述性综合。其中两项研究未报告该综述的任何预设结局。 结果综合：证据确定性 我们将证据确定性判定为低至极低。证据的主要局限性包括严重的偏倚风险（与方法报告不充分以及高或不明确的失访率相关）、非常严重的不精确性（与低事件率和宽置信区间相关，且部分效应估计值较大）以及严重的间接性（在选定的亚组中评估结局）。PRM对比安慰剂 米非司酮对比安慰剂 这些结果基于一项研究（360名受试者），该研究在三个月后测量结局。该研究未报告总体疼痛。三个月时，米非司酮可能改善痛经（OR 0.07，95% CI 0.03至0.15；1项研究，342名受试者；低确定性证据），提示如果安慰剂组中40%的女性出现痛经，那么服用米非司酮的女性中这一比例将在3%至10%之间。我们不确定米非司酮是否能改善性交痛（OR 0.23，95% CI 0.10至0.51；1项研究，223名受试者；极低确定性证据）。然而，米非司酮可能增加潮热（OR 28.79，95% CI 3.93至210.73；1项研究，360名受试者；低确定性证据）。米非司酮在治疗三个月后对恶心患病率可能几乎没有影响（OR 1.72，95% CI 0.20至15.03；1项研究，360名受试者；低确定性证据）。PRM与其他药物治疗对比 孕三烯酮对比达那唑 这些结果基于两项研究（302名受试者），这些研究在六个月后测量结局。我们不确定孕三烯酮相对于达那唑的效应。 关于总体疼痛的改善（二分类结局：报告无或轻度盆腔痛的参与者计为“改善”）（OR 0.47，95% CI 0.04至5.70；1项研究，38名参与者）、痛经（无法估计；1项研究，38名参与者）或性交痛（OR 1.00，95% CI 0.13至7.94；1项研究，38名参与者）（均为极低确定性证据）。我们不确定孕三烯酮相对于达那唑对潮热的影响（OR 0.79，95% CI 0.50至1.26；2项研究，302名参与者；极低确定性证据）。孕三烯酮与达那唑在恶心发生率方面可能几乎没有差异（OR 1.36，95% CI 0.84至2.19；2项研究，302名参与者；低确定性证据）。孕三烯酮对比GnRH类似物（亮丙瑞林）这些结果基于一项研究（55名参与者），该研究在六个月后测量了结局。孕三烯酮与亮丙瑞林在非经期疼痛方面可能几乎没有差异（MD -0.41，95% CI -1.76至0.94；1项研究，55名参与者；低确定性证据）。服用孕三烯酮的女性痛经评分可能高于服用亮丙瑞林的女性（MD 0.82，95% CI 0.15至1.49；1项研究，55名参与者；低确定性证据），但孕三烯酮在改善性交痛方面可能优于亮丙瑞林（MD -1.16，95% CI -2.08至-0.24；1项研究，52名参与者；低确定性证据）。孕三烯酮组的潮热发生率可能低于亮丙瑞林组（OR 0.20，95% CI 0.06至0.63；1项研究，55名参与者；低确定性证据）。孕三烯酮与亮丙瑞林在恶心发生率方面可能几乎没有差异（OR 1.04，95% CI 0.0 6至17.49；1项研究，55名参与者；低确定性证据）。 作者结论：米非司酮可能改善子宫内膜异位症女性的痛经，但可能增加不良事件（如潮热）的发生率。关于其对性交痛的影响，证据非常不确定。孕三烯酮治疗痛经的效果可能不如亮丙瑞林，但可能改善性交痛。它可能与较低的潮热发生率和相似的恶心发生率相关。我们不确定孕三烯酮与达那唑相比的效果。我们发现的证据不足，无法对其他孕激素受体调节剂的安全性和有效性得出确切结论。 资金：本Cochrane系统评价没有专项资助。 注册：方案（2012）DOI: 10.1002/14651858.CD009881 评价（2017）DOI: 10.1002/14651858.CD009881.pub2.
完整摘要 · 英文原文
RATIONALE: Endometriosis is defined as the presence of endometrium-like tissue developing outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects on the endometrium, progesterone receptor modulators (PRMs) have been advocated for the treatment of endometriosis. This is an update of a Cochrane review previously published in 2017. OBJECTIVES: To assess the effectiveness and safety of progesterone receptor modulators (PRMs) in the management of endometriosis. SEARCH METHODS: To identify studies, we searched online sources, including the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, ClinicalTrials.gov and the WHO (World Health Organization) trial registry up to 16 April 2026. We also checked reference lists and contacted study authors and experts. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing PRMs with placebo, no treatment or other medical treatment, in women with symptomatic endometriosis. OUTCOMES: Our critical outcomes were overall pain; improvement in the most troublesome symptom, including dysmenorrhoea and dyspareunia; and adverse events resulting from the PRM intervention. Our important outcomes included quality of life (QoL) and patient satisfaction with treatment. RISK OF BIAS: We used the Cochrane tool RoB 2 to assess the risk of bias in the outcomes of this review. SYNTHESIS METHODS: Two review authors independently assessed studies against the inclusion criteria, extracted data and assessed risk of bias, consulting a third review author where required. We analysed dichotomous outcomes using Mantel-Haenszel odds ratios (ORs), 95% confidence intervals (CIs) and the fixed-effect model. We analysed continuous outcomes using the mean difference (MD) between groups, presented with 95% CIs. We employed the GRADE approach to assess the certainty of the evidence as high, moderate, low or very low. INCLUDED STUDIES: No new studies were eligible for inclusion in this update. Of the nine studies (922 women) already included in the review, two compared mifepristone versus placebo or compared different doses of mifepristone, and four either compared gestrinone versus danazol, gestrinone versus gonadotropin-releasing hormone (GnRH) analogues or compared different doses of gestrinone. One study compared asoprisnil versus placebo. The asoprisnil study did not provide extractable numerical data and was included in the narrative synthesis only. Two of the studies did not report any of the review's prespecified outcomes. SYNTHESIS OF RESULTS: Certainty of the evidence We judged the certainty of evidence as low to very low. The main limitations of the evidence were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition), very serious imprecision (associated with low event rates and wide confidence intervals, with some large effect estimates) and serious indirectness (outcomes assessed in selected subgroups). PRM versus placebo Mifepristone versus placebo These results are based on one study (360 participants) that measured outcomes after three months. The study did not report overall pain. At three months, mifepristone may improve dysmenorrhoea (OR 0.07, 95% CI 0.03 to 0.15; 1 study, 342 participants; low-certainty evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. We are uncertain whether mifepristone improves dyspareunia (OR 0.23, 95% CI 0.10 to 0.51; 1 study, 223 participants; very low-certainty evidence). However, mifepristone may increase hot flushes (OR 28.79, 95% CI 3.93 to 210.73; 1 study, 360 participants; low-certainty evidence). Mifepristone may make little or no difference after three months of treatment to the prevalence of nausea (OR 1.72, 95% CI 0.20 to 15.03; 1 study, 360 participants; low-certainty evidence). PRM versus other medical treatment Gestrinone versus danazol These results are based on two studies (302 participants) that measured outcomes after six months. We are uncertain of the effects of gestrinone relative to danazol on the improvement of overall pain (dichotomous outcome: participants reporting no or mild pelvic pain counted as 'improved') (OR 0.47, 95% CI 0.04 to 5.70; 1 study, 38 participants), dysmenorrhoea (Not estimable; 1 study, 38 participants), or dyspareunia (OR 1.00, 95% CI 0.13 to 7.94; 1 study, 38 participants (all very low-certainty evidence). We are uncertain about the effects of gestrinone relative to danazol on hot flushes (OR 0.79, 95% CI 0.50 to 1.26; 2 studies, 302 participants; very low-certainty evidence). There may be little or no difference between gestrinone and danazol in rates of nausea (OR 1.36, 95% CI 0.84 to 2.19; 2 studies, 302 participants; low-certainty evidence). Gestrinone versus a GnRH analogue (leuprorelin) These results are based on one study (55 participants) that measured outcomes after six months. There may be little to no difference between gestrinone and leuprorelin in non-menstrual pain (MD -0.41, 95% CI -1.76 to 0.94; 1 study, 55 participants; low-certainty evidence). Women taking gestrinone may have higher dysmenorrhoea scores than those taking leuprorelin (MD 0.82, 95% CI 0.15 to 1.49; 1 study, 55 participants; low-certainty evidence), but gestrinone may improve dyspareunia more than leuprorelin (MD -1.16, 95% CI -2.08 to -0.24; 1 study, 52 participants; low-certainty evidence). There may be lower rates of hot flushes with gestrinone than leuprorelin (OR 0.20, 95% CI 0.06 to 0.63; 1 study, 55 participants; low-certainty evidence). There may be little or no difference between gestrinone and leuprorelin in rates of nausea (OR 1.04, 95% CI 0.06 to 17.49; 1 study, 55 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Mifepristone may improve dysmenorrhoea in women with endometriosis, but it might increase the prevalence of adverse events, such as hot flushes. The evidence is very uncertain regarding its effect on dyspareunia. Gestrinone may be less effective than leuprorelin in treating dysmenorrhoea, but it may improve dyspareunia. It may be associated with lower rates of hot flushes and similar rates of nausea. We are uncertain about the effect of gestrinone compared to danazol. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2012) DOI: 10.1002/14651858.CD009881 Review (2017) DOI: 10.1002/14651858.CD009881.pub2.