Menopausal hormone therapy and women's health: An umbrella review.
Menopausal hormone therapy and women's health: An umbrella review.
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DOI：
10.1371/journal.pmed.1003731
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发表时间：
2021-08
期刊：
影响因子：
15.8
通讯作者：
Nwaru BI
中科院分区：
文献类型：
--
作者：
Zhang GQ;Chen JL;Luo Y;Mathur MB;Anagnostis P;Nurmatov U;Talibov M;Zhang J;Hawrylowicz CM;Lumsden MA;Critchley H;Sheikh A;Lundbäck B;Lässer C;Kankaanranta H;Lee SH;Nwaru BI
绝经期激素治疗（MHT）对妇女健康的影响仍然不确定。缺乏对多种结果影响的系统、全面评估。我们进行了一项总括性审查，以全面总结MHT在不同健康结果中的益处和危害的证据。我们检索了MEDLINE，EMBASE和其他10个数据库，从开始到2017年11月26日，更新于2020年12月17日，以确定随机对照试验（RCT）和观察性研究的系统综述或荟萃分析，这些研究调查了MHT的影响，包括雌激素单药治疗（ET）和雌激素加孕酮治疗（EPT），在所有国家和地区的围绝经期或绝经后妇女中。纳入了既往系统评价中的所有健康结局，包括绝经期症状、替代终点、生物标志物、各种发病率结局和死亡率。两名研究者独立提取数据，并使用更新的16项AMSTAR 2工具评估系统评价的方法学质量。随机效应稳健方差估计用于联合收割机效应估计，并尽可能计算95%预测区间（PI）。我们使用术语MHT来涵盖ET和EPT，并且除非另有说明，否则每个结局的结果都是针对MHT的。纳入了60篇系统性综述，涉及102项RCT荟萃分析和38项观察性研究，有102项独特结局。纳入的系统性综述的总体质量为中等至较差。在RCT的荟萃分析中，MHT对血管痉挛症状有益（频率：9项试验，1，104名女性，风险比[RR] 0.43，95%CI 0.33至0.57，p < 0.001;严重程度：7项试验，503名女性，RR 0.29，95% CI 0.17至0.50，p = 0.002），所有骨折（30项试验，43，188名女性，RR 0.72，95% CI 0.62至0.84，p = 0.002，95% PI 0.58至0.87），以及阴道萎缩（阴道内ET）、性功能、椎骨和非椎骨骨折、糖尿病、心血管死亡率（ET）和结直肠癌（EPT），但对中风有害（17项试验，37，272名女性，RR 1.17，95% CI 1.05 - 1.29，p = 0.027）和静脉血栓栓塞（23项试验，42，292名女性，RR 1.60，95% CI 0.99至2.58，p = 0.052，95% PI 1.03至2.99），以及心血管疾病的发病率和复发率、脑血管疾病、非致死性卒中、深静脉血栓形成、需要手术的胆囊疾病和肺癌死亡率（EPT）。在观察性研究的荟萃分析中，MHT与白内障、神经胶质瘤、食管癌、胃癌和结直肠癌的风险降低相关，但与肺栓塞、胆石症、哮喘、脑膜瘤、甲状腺癌、乳腺癌和卵巢癌的风险增加相关。ET和EPT对子宫内膜癌、子宫内膜增生和阿尔茨海默病的作用相反。主要局限性包括无法解决MHT类型、剂量、剂型、使用持续时间、给药途径和开始使用年龄的不同影响，以及无法考虑系统性综述中纳入的个体研究的质量。研究方案可在PROSPERO（CRD 42017083412）上公开获取。MHT对多种健康结果的益处和危害具有复杂的平衡。ET和EPT之间的一些效应在性质上不同。现有证据的质量仅为中等至较差。在一项总括性综述中，Guo-Qiang Zhang及其同事全面总结了绝经期激素治疗在不同健康结果中的益处和危害的证据。据估计，到2050年，全世界将有超过16亿妇女达到更年期或绝经后，而2020年为10亿。高达75%的更年期妇女受到困扰的更年期症状，如潮热和盗汗。月经激素治疗（MHT）是缓解更年期症状最有效的治疗方法，但其对许多健康结果的影响仍不确定。我们纳入了60篇已发表的关于绝经期妇女使用MHT的系统综述，涉及102项随机对照试验的荟萃分析和38项观察性研究，并综合了102项健康结局的证据。总的来说，MHT具有复杂的利益和危害平衡;例如，除了缓解更年期症状外，它还与骨折，糖尿病，食管癌，胃癌和结直肠癌的风险降低有关，但增加了中风，静脉血栓栓塞，胆囊疾病，乳腺癌和卵巢癌的风险。支持MHT降低年龄<60岁或绝经后10年内女性冠心病风险和全因死亡率的现有临床数据（称为“时间假说”）仅具有提示性。纳入的系统性综述的总体质量为中等至较差。这种证据景观的概述可以帮助指南制定者和决策者更好地理解与绝经期妇女使用MHT相关的益处和危害之间的权衡。需要更多的数据来评估冠心病和全因死亡率的时间假说。临床医生在考虑将其结果应用于临床实践之前，应评估系统评价的科学强度。
There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women’s health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor. In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes. By 2050, it is estimated that worldwide more than 1.6 billion women will have reached menopause or be postmenopausal, up from 1 billion in 2020. Up to 75% of menopausal women are affected by bothersome menopausal symptoms, such as hot flashes and night sweats. Menopausal hormone therapy (MHT) is the most effective treatment for alleviating menopausal symptoms, but its effects on numerous health outcomes remain uncertain. We included 60 published systematic reviews of MHT use in menopausal women, involving 102 meta-analyses of randomized controlled trials and 38 of observational studies, and synthesized the evidence on 102 health outcomes. Overall, MHT had a complex balance of benefits and harms; for example, beyond alleviation of menopausal symptoms, it was associated with decreased risks of bone fracture, diabetes mellitus, and esophageal, gastric, and colorectal cancer, but increased risks of stroke, venous thromboembolism, gallbladder disease, and breast and ovarian cancer. The available clinical data in support of MHT reducing the risk of coronary heart disease and all-cause mortality in women aged <60 years or within 10 years from menopause (known as the “timing hypothesis”) were only suggestive. The overall quality of included systematic reviews was moderate to poor. This overview of the evidence landscape could help guideline developers and decision-makers better appreciate the trade-offs between the benefits and harms associated with MHT use in menopausal women. More data are needed to evaluate the timing hypothesis for coronary heart disease and all-cause mortality. Clinicians should evaluate the scientific strength of systematic reviews prior to considering applying their results in clinical practice.
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影响因子：
15.1
作者：
Delaney, A;Bagshaw, SM;Ferland, A;Manns, B;Laupland, KB;Doig, CJ
通讯作者：
Doig, CJ
影响因子：
4.7
作者：
Brieger, Katharine K.;Peterson, Siri;Pearce, Celeste Leigh
通讯作者：
Pearce, Celeste Leigh
影响因子：
158.5
作者：
Cohen, JC;Boerwinkle, E;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
120.7
作者：
Chlebowski, Rowan T.;Anderson, Garnet L.;Prentice, Ross L.
通讯作者：
Prentice, Ross L.
DOI：
10.1097/gme.0b013e3182843aad
发表时间：
2013-03-01
影响因子：
2.7
作者：
Clarkson, Thomas B.;Melendez, Giselle C.;Appt, Susan E.
通讯作者：
Appt, Susan E.