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Article(id=1241522776117408677, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522764012647140, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202307423, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1690041600000, receivedDateStr=2023-07-23, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773931696204, onlineDateStr=2026-03-19, pubDate=1704816000000, pubDateStr=2024-01-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773931696204, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773931696204, creator=13701087609, updateTime=1773931696204, updator=13701087609, issue=Issue{id=1241522764012647140, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='1', pageStart='1', pageEnd='192', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773931693318, creator=13701087609, updateTime=1773931808852, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241523248643494379, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522764012647140, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241523248643494380, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522764012647140, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=173, endPage=179, ext={EN=ArticleExt(id=1241522776549422029, articleId=1241522776117408677, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Meta-analysis of the relationship between estrogen replacement therapy and ovarian cancer in postmenopausal women, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To systematically evaluate the risk of estrogen use and ovarian cancer in postmenopausal women.

Methods

PubMed, Cochrane, Embase databases and Chinese databases such as CNKI, VIP, and Wan fang were searched by computer. Studies on the correlation between estrogen replacement therapy and ovarian cancer in postmenopausal women up until January 2023 were collected. The methodological quality of the study was evaluated by Stata software and the effective data were extracted for meta-analysis. We used the odds ratio (OR) and its corresponding 95% confidence interval (CIs) to evaluate the relationship between hormone replacement therapy and ovarian cancer. When there was statistical heterogeneity between studies (P≤0.1 and I2≥ 40%), random effect model was used for meta-analysis; otherwise, fixed effect model was used for analysis.

Results

A total of 14 retrospective studies including 10 cohort studies and 4 case-control studies were identified. Meta-analysis showed that postmenopausal estrogen therapy increased the risk of ovarian cancer in women (OR=1.27, 95%CI: 1.14-1.43). Stratified analysis showed that there was no significant increase in the risk of ovarian cancer in postmenopausal women who took estrogen for less than 5 years (OR=1.04, 95%CI: 0.90-1.20). Postmenopausal women who received estrogen treatment for 5 to 10 years had a significantly increased risk of developing ovarian cancer (OR=1.27, 95%CI: 1.06-1.53). Postmenopausal women who had been treated with estrogen for more than 10 years had a significantly increased risk of ovarian cancer (OR=1.69, 95%CI: 1.42-2.02).

Conclusion

The risk of ovarian cancer in postmenopausal women treated with estrogen replacement therapy is related to the course of estrogen therapy. There is no significant increase in the risk of ovarian cancer within 5 years, but the risk of ovarian cancer is significantly increased when the course of treatment exceeds 5 years.

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目的

系统评价绝经后妇女服用雌激素与罹患卵巢癌的风险。

方法

计算机检索PubMed、Cochrane和Embase数据库及CNKI、维普、万方等中文数据库，收集绝经后女性雌激素补充治疗与卵巢癌相关性的研究，采用Stata软件评价纳入研究的方法学质量并提取有效数据进行meta分析。文献检索时限截至2023年1月，采用比值比（OR）及其相应的95%置信区间(CI)来评估激素补充治疗与卵巢癌之间的关系。当研究间存在统计学异质性（P≤0.1，I2≥ 40%）时，采用随机效应模型进行meta分析；否则采用固定效应模型进行分析。

结果

共纳入14项回顾性研究，其中包括10项队列研究，4项病例对照研究。Meta分析结果显示绝经后雌激素治疗将增加女性罹患卵巢癌的风险（OR=1.27，95%CI：1.14～1.43）。分层分析结果显示：服用雌激素疗程<5年的绝经后女性，其卵巢癌风险无明显增加，（OR=1.04，95%CI：0.90～1.20）。雌激素疗程在5～10年间的绝经后女性，其罹患卵巢癌的风险明显增加（OR=1.27，95%CI：1.06～1.53)。而雌激素疗程在10年以上的绝经后女性罹患卵巢癌的风险显著增加（OR=1.69，95%CI：1.42～2.02)。

结论

绝经后妇女使用雌激素补充治疗与卵巢癌的风险同雌激素治疗的疗程相关，疗程在5年以内卵巢癌风险无明显增加，疗程≥5年则罹患卵巢癌的风险明显增加。

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陈杰，E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=ZAOm2qtGFihOgmnsAacrEA==, magXml=p3W91B76WC3265v0eODrcQ==, pdfUrl=null, pdf=+F9Ajoq0x5I2VABo9uFGBA==, pdfFileSize=2097502, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=j6id4fF13SRR1qf6kwCuCA==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=7Oc86HW6ft2tA8bHEMhpwA==, mapNumber=null, authorCompany=null, fund=null, authors=

郑曦（1997-），女，硕士在读，研究方向：妇产科常见疾病

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郑曦（1997-），女，硕士在读，研究方向：妇产科常见疾病

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郑曦（1997-），女，硕士在读，研究方向：妇产科常见疾病

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Characteristics of studies included in this meta-analysis

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文献（发表时间）研究类型地区研究时间（年）平均年龄（岁）总人数卵巢癌例数
Sit2002[10]病例对照研究美国1994—199856.21 41045
Lacey2002[14]队列研究美国1979—199856.644 241116
Riman2002[15]队列研究瑞典1993—199563.24 55459
Folsom2004[17]队列研究美国1987—199759.741 83672
Bakken2004[16]队列研究挪威1996—199858.31 54218
Moorman2005[18]病例对照研究美国1999—200361.8734105
Lacey2006[19]队列研究美国1995—199762.597 63849
Rossing2007[21]病例对照研究美国2002—200557.22 125167
Danforth2007[20]队列研究美国1976—200262.04 315137
Mo/ rch2009[12]队列研究丹麦1995—200562.1909 9461 725
Hildebrand2010[22]队列研究美国1997—200761.454 43693
Tsilidis2011[23]队列研究欧洲2003—200651.26 74529
Felix2015[24]队列研究美国1995—199761.8556 38994
Bryk2021[25]病例对照研究芬兰1994—201560.11 36211
), ArticleFig(id=1241677625563869266, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522776117408677, language=CN, label=表1, caption=

纳入文献基本信息

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文献（发表时间）研究类型地区研究时间（年）平均年龄（岁）总人数卵巢癌例数
Sit2002[10]病例对照研究美国1994—199856.21 41045
Lacey2002[14]队列研究美国1979—199856.644 241116
Riman2002[15]队列研究瑞典1993—199563.24 55459
Folsom2004[17]队列研究美国1987—199759.741 83672
Bakken2004[16]队列研究挪威1996—199858.31 54218
Moorman2005[18]病例对照研究美国1999—200361.8734105
Lacey2006[19]队列研究美国1995—199762.597 63849
Rossing2007[21]病例对照研究美国2002—200557.22 125167
Danforth2007[20]队列研究美国1976—200262.04 315137
Mo/ rch2009[12]队列研究丹麦1995—200562.1909 9461 725
Hildebrand2010[22]队列研究美国1997—200761.454 43693
Tsilidis2011[23]队列研究欧洲2003—200651.26 74529
Felix2015[24]队列研究美国1995—199761.8556 38994
Bryk2021[25]病例对照研究芬兰1994—201560.11 36211
), ArticleFig(id=1241677625714864217, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522776117408677, language=EN, label=Table 2, caption=

Quality assessment of case-control studies included in this meta-analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
纳入研究病例定义是否充分病例的代表性对照的选择对照的定义病例和对照的可比性a暴露的评估和调查方法b病例和对照的调查方法是否相同无应答率质量评价c
Riman2002[15]★★★★★☆★★★9
Lacey2002[14]★—★★★☆★★—7
Sit2002[10]★★★★★☆★★—8
Folsom2004[17]★★★★★☆★★★9
Bakken2004[16]★★★★★☆★★—8
Moorman2005[18]★★★★★★★★8
Lacey2006[19]★★★★★☆★★★9
Rossing2007[21]★★★★★★★★8
Danforth2007[20]★★★★★☆★★—8
Mo/ rch2009[12]★★★★★☆★★★9
Hildebrand2010[22]★★★★★☆★★★9
Tsilidis2011[23]★★★★★★★—7
Felix2015[24]★★★★★★★★8
Bryk2021[25]★★★★★☆★★★9
), ArticleFig(id=1241677625886830688, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522776117408677, language=CN, label=表2, caption=

纳入研究的质量评价

, figureFileSmall=null, figureFileBig=null, tableContent=
纳入研究病例定义是否充分病例的代表性对照的选择对照的定义病例和对照的可比性a暴露的评估和调查方法b病例和对照的调查方法是否相同无应答率质量评价c
Riman2002[15]★★★★★☆★★★9
Lacey2002[14]★—★★★☆★★—7
Sit2002[10]★★★★★☆★★—8
Folsom2004[17]★★★★★☆★★★9
Bakken2004[16]★★★★★☆★★—8
Moorman2005[18]★★★★★★★★8
Lacey2006[19]★★★★★☆★★★9
Rossing2007[21]★★★★★★★★8
Danforth2007[20]★★★★★☆★★—8
Mo/ rch2009[12]★★★★★☆★★★9
Hildebrand2010[22]★★★★★☆★★★9
Tsilidis2011[23]★★★★★★★—7
Felix2015[24]★★★★★★★★8
Bryk2021[25]★★★★★☆★★★9
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郑曦 , 易棵 , 陈杰
现代预防医学 | 临床与预防 2024,51(1): 173-179
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现代预防医学 | 临床与预防 2024, 51(1): 173-179
绝经后女性雌激素补充疗法与卵巢癌相关性Meta分析
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郑曦, 易棵, 陈杰
作者信息
  • 四川大学华西第二医院妇产科，四川 成都 610041

    • 郑曦（1997-），女，硕士在读，研究方向：妇产科常见疾病

通讯作者:

陈杰，E-mail:
Meta-analysis of the relationship between estrogen replacement therapy and ovarian cancer in postmenopausal women
Xi ZHENG, Ke YI, Jie CHEN
Affiliations
  • Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, Sichuan 610041, China
出版时间: 2024-01-10 doi: 10.20043/j.cnki.MPM.202307423
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摘要
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目的

系统评价绝经后妇女服用雌激素与罹患卵巢癌的风险。

方法

计算机检索PubMed、Cochrane和Embase数据库及CNKI、维普、万方等中文数据库，收集绝经后女性雌激素补充治疗与卵巢癌相关性的研究，采用Stata软件评价纳入研究的方法学质量并提取有效数据进行meta分析。文献检索时限截至2023年1月，采用比值比（OR）及其相应的95%置信区间(CI)来评估激素补充治疗与卵巢癌之间的关系。当研究间存在统计学异质性（P≤0.1，I2≥ 40%）时，采用随机效应模型进行meta分析；否则采用固定效应模型进行分析。

结果

共纳入14项回顾性研究，其中包括10项队列研究，4项病例对照研究。Meta分析结果显示绝经后雌激素治疗将增加女性罹患卵巢癌的风险（OR=1.27，95%CI：1.14～1.43）。分层分析结果显示：服用雌激素疗程<5年的绝经后女性，其卵巢癌风险无明显增加，（OR=1.04，95%CI：0.90～1.20）。雌激素疗程在5～10年间的绝经后女性，其罹患卵巢癌的风险明显增加（OR=1.27，95%CI：1.06～1.53)。而雌激素疗程在10年以上的绝经后女性罹患卵巢癌的风险显著增加（OR=1.69，95%CI：1.42～2.02)。

结论

绝经后妇女使用雌激素补充治疗与卵巢癌的风险同雌激素治疗的疗程相关，疗程在5年以内卵巢癌风险无明显增加，疗程≥5年则罹患卵巢癌的风险明显增加。

绝经后  /  雌激素补充治疗  /  卵巢癌  /  系统评价
Objective

To systematically evaluate the risk of estrogen use and ovarian cancer in postmenopausal women.

Methods

PubMed, Cochrane, Embase databases and Chinese databases such as CNKI, VIP, and Wan fang were searched by computer. Studies on the correlation between estrogen replacement therapy and ovarian cancer in postmenopausal women up until January 2023 were collected. The methodological quality of the study was evaluated by Stata software and the effective data were extracted for meta-analysis. We used the odds ratio (OR) and its corresponding 95% confidence interval (CIs) to evaluate the relationship between hormone replacement therapy and ovarian cancer. When there was statistical heterogeneity between studies (P≤0.1 and I2≥ 40%), random effect model was used for meta-analysis; otherwise, fixed effect model was used for analysis.

Results

A total of 14 retrospective studies including 10 cohort studies and 4 case-control studies were identified. Meta-analysis showed that postmenopausal estrogen therapy increased the risk of ovarian cancer in women (OR=1.27, 95%CI: 1.14-1.43). Stratified analysis showed that there was no significant increase in the risk of ovarian cancer in postmenopausal women who took estrogen for less than 5 years (OR=1.04, 95%CI: 0.90-1.20). Postmenopausal women who received estrogen treatment for 5 to 10 years had a significantly increased risk of developing ovarian cancer (OR=1.27, 95%CI: 1.06-1.53). Postmenopausal women who had been treated with estrogen for more than 10 years had a significantly increased risk of ovarian cancer (OR=1.69, 95%CI: 1.42-2.02).

Conclusion

The risk of ovarian cancer in postmenopausal women treated with estrogen replacement therapy is related to the course of estrogen therapy. There is no significant increase in the risk of ovarian cancer within 5 years, but the risk of ovarian cancer is significantly increased when the course of treatment exceeds 5 years.

Postmenopausal  /  Estrogen replacement therapy  /  Ovarian cancer  /  Systematic review
郑曦, 易棵, 陈杰. 绝经后女性雌激素补充疗法与卵巢癌相关性Meta分析. 现代预防医学, 2024 , 51 (1) : 173 -179 . DOI: 10.20043/j.cnki.MPM.202307423
Xi ZHENG, Ke YI, Jie CHEN. Meta-analysis of the relationship between estrogen replacement therapy and ovarian cancer in postmenopausal women[J]. Modern Preventive Medicine, 2024 , 51 (1) : 173 -179 . DOI: 10.20043/j.cnki.MPM.202307423
正文
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卵巢癌是妇科常见三种恶性肿瘤之一，约占女性癌症死亡人数的5 %，而其导致的死亡人数超过另外两种妇科恶性肿瘤宫颈癌和子宫内膜癌[1-2]。目前已知卵巢癌的危险因素包括高龄、卵巢癌家族史和BRCA1和BRCA2基因突变等[3-4]。除了遗传因素，与卵巢癌发病风险相关的环境因素包括高脂饮食、吸烟、肥胖和激素补充疗法等[5-6]。
随着雌激素补充疗法在绝经后女性的应用，学者们试图探索其与卵巢癌发病风险的相关性[7]。一些流行病学研究报道，绝经后妇女使用雌激素补充治疗将增加其罹患卵巢癌的风险[8-9]。但Sit等[10]发表的病例对照研究却发现绝经后女性服用雌激素并不增加卵巢癌的风险。然而病例对照研究的样本量相对较小，其研究结果存在一定局限性。
Coughlin等[11]在2000年发表了一篇关于绝经后妇女雌激素补充疗法与卵巢癌风险的meta分析，结果显示雌激素补充疗法与卵巢癌的发生无明显相关性。此后有更多的研究报道了绝经后女性服用雌激素与卵巢癌的相关性，Corson等[12]报道了一项大样本的队列研究，发现绝经后妇女服用雌激素将明显增加卵巢癌风险。目前关于绝经后女性雌激素补充治疗与卵巢癌的相关性仍存在争议，本研究的目的是对已发表的雌激素补充治疗与卵巢癌相关性的研究进行meta分析，以确定雌激素补充治疗是否增加绝经后女性罹患卵巢癌的风险，并针对不同疗程进行分层分析。
1　对象与方法
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1.1　文献检索
计算机检索英文数据库Pubmed、Embase、Cochrane，检索词组配：（hormone therapy or estrogen therapy）and（menopausal or postmenopausal）and（ovarian cancer or ovarian neoplasm)。检索中文科技期刊全文数据库（VIP）、中国期刊全文数据库（CNKI）、万方、中国生物医学文献数据库（CBM），检索词组配：（雌激素or雌二醇or激素替代）and（绝经后or围绝经期or更年期）and（卵巢癌or卵巢恶性肿瘤）。检索时限从各数据库建库至2023年1月。方法采用主题检索结合自由检索。文献检索由两名研究者分别独立进行，检索的文献根据PRISMA指南进行筛选。
1.2　纳入及排除标准
纳入标准：( 1 )前瞻性和回顾性研究；( 2 )参与者均为服用雌激素治疗的绝经后妇女；( 3 )提供量化结果数据。排除标准：( 1 )摘要、综述及概述; ( 2 )非病例对照研究，( 3 )数据资料不全或错误。
1.3　数据提取
从纳入研究中提取的数据包括第一作者姓名、发表年份、研究设计和国家、研究周期、平均年龄、参与人数、卵巢癌病例数。由两名研究者分别独立从符合条件的研究中提取数据，若两名究者产生意见分歧，则讨论解决或由第三名研究者仲裁。
1.4　文献质量评价
纳入文献的质量评价采用Newcastle-Ottawa scale (NOS)文献质量评价量表对纳入研究的质量进行评估[13]。质量评估主要从病例定义是否充分，病例的代表性，对照的选择，对照的定义，病例和对照的可比性，暴露的评估和调查方法，病例和对照的调查方法是否相同和无应答率8个方面进行，共10分；文献质量评分<6分，认为文献质量较低，质量评分≥6分的认为文献质量较高。纳入研究的质量评价由两名研究者独立进行，分歧由第三名研究者仲裁解决。
1.5　结局指标和数据分析
本研究的主要结果是雌激素治疗与卵巢癌的相关性。计数资料采用比值比（OR）为疗效分析统计量，各效应量均以95%可信区间（CI）表示。采用χ2检验分析各研究间的异质性。当各研究间存在统计学异质性（P≤0.1，I2≥40%）时，采用随机效应模型进行meta分析；否则采用固定效应模型进行meta分析。
1.6　发表偏倚
如果纳入研究超过5项，则通过构建漏斗图和Egger检验来评估发表偏倚。若数据点呈对称漏斗状分布，且P>0.05，表明无发表偏倚。
2　结果
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2.1　文献检索结果
根据主题词共检索出相关文献49篇，排除重复文献22篇，排除病例报道及其他非相关文献9篇。随后全文阅读共18篇文章，排除4篇，其原因及检索流程见图1。最终纳入14篇文献[10,12,14-25]。表1概述了雌激素替代治疗的研究特点、类型和治疗方案、卵巢癌病例数和肿瘤亚型。在14篇文献中，10篇是队列研究，包括1 721 642名妇女和2 392名卵巢癌患者；4篇是病例对照研究，包括1 793名卵巢癌患者和4 435名对照者。
2.2　文献质量评价
表2展示了采用NOS量表进行质量评价的结果，纳入研究的14篇文献的质量评价均高于6分，总体质量较高，降低了产生偏倚的风险。
2.3　Meta分析结果
Meta分析结果显示纳入的14项研究间存在异质性（I2=45.8%，P=0.031），因此采用随机效应模式进行分析，结果显示绝经后雌激素治疗将增加女性罹患卵巢癌的风险(OR=1.27，95%CI：1.14～1.43)，见图2。
根据雌激素治疗的持续时间将研究进行分层分析，雌激素疗程小于5年的研究有8项，meta分析结果显示服用雌激素疗程小于5年的绝经后女性与不使用雌激素的女性相比，其罹患卵巢癌风险无明显差异（OR=1.04，95%CI：0.90～1.20），见图3。
雌激素疗程在5～10年间的研究有9项，结果显示雌激素疗程在5～10年间的绝经后女性，其罹患卵巢癌的风险明显增加(OR=1.27，95%CI：1.06～1.53)，见图4。
而雌激素疗程在10年以上的研究有6项，meta分析结果显示雌激素疗程在10年以上的绝经后女性罹患卵巢癌的风险显著增加(OR=1.69，95%CI：1.42～2.02)，见图5。
2.4　异质性分析
总体分析结果显示纳入研究的14项研究之间存在较为明显的异质性（I2=45.8%，P=0.031），我们采用星状图分析异质性来源，发现异质性主要源于两项研究[10,22]，见图6。当去除上述这两项研究后，再次进行meta分析，结果显示异质性显著降低（I2=0.1%，P=0.623），而meta分析的结果仍提示绝经后女性雌激素治疗将增加其罹患卵巢癌风险(OR=1.28，95%CI：1.18～1.39)。
2.5　发表偏倚
纳入文献的发表偏倚采用Begg检验和Egger检验予以评估。漏斗图中没有发现明显的不对称，见图7统计结果中未发现发表偏倚：Begg检验P=0.584；Egger检验P=0.805。
3　讨论
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绝经后妇女由于体内雌孕激素水平明显下降，出现涉及多个系统的多种绝经相关症状，并与骨质疏松等许多大量占用医疗资源的老年慢性疾病相关，近年越来越受到专业人士和大众的关注[26-28]。激素补充治疗可以有效缓解绝经相关症状，且在绝经早期（即治疗的窗口期）使用激素补充治疗可以在一定程度上预防老年慢性疾病发生。但对于激素补充治疗的副作用仍存在争议[29-32]。
本文纳入14项针对绝经后女性使用雌激素与卵巢癌相关性的高质量研究，meta分析结果提示绝经后使用雌激素将增加妇女罹患卵巢癌的风险(OR=1.27，95%CI：1.14～1.43)。这与2015年一项激素补充治疗与卵巢癌风险的meta分析的结果是一致的，该meta分析纳入11篇雌激素补充治疗与卵巢癌风险的文献，结果显示绝经后使用雌激素将增加妇女罹患卵巢癌的风险(OR=1.37，95%CI：1.19～1.58)[33]。2008年Pearce等[34]发表的一项包括14项研究的综述显示，绝经后妇女使用雌激素补充治疗，其罹患卵巢癌风险增加，OR为1.22。
2000年一项关于雌激素补充治疗与卵巢癌风险的meta分析结果显示雌激素补充治疗与罹患卵巢无明显相关性[11]。该meta分析的结果与本研究结果不一致，其可能的原因是由于该meta分析所纳入的文献较少（纳入有完整数据的病例对照研究仅9项），故而该研究受限于样本量难以发现统计学差异，而本研究纳入病例对照研究14项，因此所得到的结果较前更加准确和稳定。且2000年的这项meta分析并未对纳入文献中妇女使用激素补充治疗的疗程进行描述和分析，而雌激素使用的周期可能与其副作用的发生密切相关。因此我们对纳入的14项研究，根据雌激素补充治疗的疗程分为三个亚组，分别是疗程<5年，5≤疗程<10年，疗程≥10年；一项研究所统计的疗程为<4年和≥4年，故未纳入亚组分析[12]。在剩余13项研究中，雌激素疗程<5年的研究有8项，meta分析结果显示服用雌激素疗程<5年的绝经后女性与不使用雌激素的女性相比，其罹患卵巢癌风险无明显差异(OR=1.04，95%CI：0.90～1.20，P=0.183)。雌激素疗程在5～10年间的研究有9项，meta分析结果显示雌激素疗程在5～10年间的绝经后女性，其罹患卵巢癌的风险明显增加(OR=1.27，95%CI：1.06～1.53，P=0.031)。而雌激素疗程≥10年的研究有6项，meta分析结果显示雌激素疗程在10年以上的绝经后女性罹患卵巢癌的风险显著增加(OR=1.69，95%CI：1.42～2.02)。由此可以发现绝经后女性雌激素补充治疗的疗程与卵巢癌存在相关性，疗程在5年以内，并不明显增加卵巢癌的风险，但疗程在5年以上，则其罹患卵巢癌的几率明显增加，且风险随着疗程的增加而增大。
绝经后女性雌激素补充疗法（MHT）被广泛用于减轻绝经后的不适症状，如潮热、情绪波动和骨密度降低等[35-37]。尽管MHT有其显著的好处，但其对卵巢癌风险的关联及发病机制存在争议[9]。有研究报道雌激素能促进卵巢上皮细胞的增殖，绝经后的女性由于缺乏天然雌激素，当接受MHT时，体内的雌激素水平增加，可能会增强上皮细胞的增殖，从而提高卵巢癌的风险。此外，雌激素可能通过直接或间接方式干扰DNA修复机制，导致DNA损伤和突变，进而增加卵巢癌的发病风险[38-39]。另一方面，炎症在许多癌症中都起到关键作用。雌激素可能通过增加炎症反应来增加卵巢癌的风险[40]。炎症环境可能导致产生活性氧和自由基，这些物质能损伤DNA，进一步增加癌变风险。但也有研究指出，MHT中添加的孕激素可能对卵巢有保护作用。与雌激素相比，孕激素具有相反的效应，可能通过抑制卵巢上皮细胞的增殖和促进细胞凋亡，从而降低卵巢癌的风险[41-42]。总的来说，关于MHT与卵巢癌风险的关联需要进一步的研究。为了更好地理解这种关联，未来的研究应当考虑MHT的类型、剂量、使用时长以及与孕激素的联合应用[43]。
Meta分析的一个重要的关注点是异质性的程度，因为非均质的研究进行合并分析可能会产生误导性的结果。在本研究中，通过I2统计量和Q检验来评估纳入文献的异质性，发现14项研究之间存在明显的异质性（I2=45.8%，P=0.031），我们采用星状图探索异质性来源，发现两项研究是异质性主要来源。剔除这两项研究后，异质性显著降低，而meta分析的结果保持不变。Meta分析的另一个关注点是由于文献的选择性发表而导致发表偏倚。在本研究中，对发表偏倚进行Begg漏斗图和Egger检验。无论是统计结果还是漏斗图形状，均未出现发表偏倚的迹象。
本文纳入的大部分研究中，患者接受雌激素补充治疗的方案为口服结合雌激素，有一项研究除口服结合雌激素外，还纳入了口服替勃龙治疗的患者[12]，不同类型的雌激素可能具有不同的生物活性和作用机制，这可能影响其与卵巢癌之间的关联。结合雌激素与替勃龙在雌激素受体结合亲和力上存在差异，这可能导致它们在卵巢组织中的作用不同，从而影响患者的卵巢癌风险。其次，不同的雌激素补充方式可能导致药物在体内的代谢动力学和生物利用度发生变化，进而影响其对卵巢癌风险的调节作用。除口服雌激素外，一项研究纳入了通过阴道途径补充雌激素的患者[12]，口服给药和阴道给药可能导致药物在血液中的浓度和持续时间不同，这可能对卵巢组织产生不同的影响，进而影响卵巢癌的发生率。因此，在后续研究中还需要对服用不同类型的雌激素和不同的雌激素补充方式的药代动力学和药效学特性进行比较分析，以进一步探讨其可能对卵巢癌相关性的影响。
本研究存在一定的局限性：（1）本研究纳入的文献包括病例对照研究和队列研究，均为回顾性研究，相比于前瞻性研究，尤其是随机对照研究，其结果的说服力相对较低。（2）纳入研究的文献之间存在明显的异质性，按照雌激素疗程进行分层分析，各亚组纳入的文献相对较少，样本量相对较小，可能无法发现统计学差异。（3）纳入文献的主要结果指标是OR值，OR除了雌激素补充治疗外还受其他因素影响，但并非所有纳入的文献都针对其他因素对OR进行了校正。即使有的文献对OR进行了校正，但其针对的因素比如年龄、吸烟史、体重指数和种族等不尽相同，由此可能产生偏倚。
绝经后女性雌激素补充治疗同其罹患卵巢癌的风险，与雌激素补充治疗的疗程相关。疗程小于5年，其患卵巢癌的风险无明显增高，疗程超过5年，其罹患卵巢癌的风险明显增高。但由于潜在的混杂因素众多，后续需要更多的文献进一步研究证实和丰富现有的研究结果。
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doi: 10.20043/j.cnki.MPM.202307423
  • 接收时间：2023-07-23
  • 首发时间：2026-03-19
  • 出版时间：2024-01-10
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    四川大学华西第二医院妇产科，四川 成都 610041

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
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species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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