Menopause hormone therapy and type 2 diabetes risk and prognosis: systematic review and meta-analyses.

This study was conducted to systematically review the literature, to summarise and quantify the effect of MHT on glucose or insulin levels and on new-onset type 2 diabetes among women without type 2 diabetes and to summarise and quantify the effect of MHT on glucose, insulin, lipid and blood pressure levels among women with type 2 diabetes.

本研究旨在系统回顾文献，总结并量化MHT对无2型糖尿病女性的葡萄糖或胰岛素水平以及新发2型糖尿病的影响，以及总结并量化MHT对有2型糖尿病女性的葡萄糖、胰岛素、脂质和血压水平的影响。

Methods

Data from six electronic databases (PubMed, Embase, Cochrane, CINAHL, PsyclNFO and MEDLINE) from inception to 29 July 2025 were searched for randomised controlled trials (RCTs) and cohort studies comparing MHT users with non-users among postmenopausal women or women undergoing the menopausal transition.

从六个电子数据库（PubMed、Embase、Cochrane、CINAHL、PsyclNFO和MEDLINE）中检索了从创建到2025年7月29日的数据，以寻找比较更年期女性或经历更年期过渡的女性中MHT使用者与非使用者的随机对照试验（RCTs）和队列研究。

Eligible studies reported the effects of MHT on glucose metabolism, lipid levels or blood pressure in women with or without type 2 diabetes.

符合条件的研究报告了MHT对有或无2型糖尿病女性的葡萄糖代谢、脂质水平或血压的影响。

The risk of bias in RCTs and cohort studies was assessed with version 2 of the Cochrane risk-of-bias for randomised trials (RoB 2) tool and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool, respectively.

使用Cochrane随机试验风险偏倚工具（RoB 2）版本2和干预措施的非随机研究偏倚风险工具（ROBINS-I），分别评估了随机对照试验（RCTs）和队列研究中的偏倚风险。

Certainty of evidence (CoE) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

证据的确定性（CoE）是通过推荐等级、证据质量评估、发展和评价（GRADE）方法进行评估的。

Random-effects models were used to estimate the pooled effects.

使用随机效应模型来估计汇总效应。

Results

In total, 49 articles (33 reporting on RCTs and 16 on cohort studies) from 15 countries were identified, involving 1,472,277 participants.

总共识别出49篇文章（33篇报告了RCTs，16篇报告了队列研究），来自15个国家，涉及1,472,277名参与者。

The study durations ranged from 1 week to 13.2 years for RCTs and from 6 months to 17 years for cohort studies.

研究持续时间从1周到13.2年不等，对于随机对照试验(RCTs)，从6个月到17年不等，对于队列研究。

Seven of these were assessed as having a low risk of bias.

其中七项被评估为低偏倚风险。

Among women without type 2 diabetes, MHT use was associated with small reductions in fasting insulin (11 studies: N=4262, mean difference [MD] -5.90 pmol/l [95% confidence interval(CI) -8.03, -3.77 pmol/l]; high CoE) and in homeostasis model assessment of insulin resistance score (four studies: N=2883, MD -0.21 [95% CI -0.32, -0.09]; moderate CoE), as well as a lower risk of new-onset type 2 diabetes (14 studies: N=1,450,134, risk ratio 0.83 [95% CI 0.75, 0.92]; very low CoE], compared with non-MHT users.

在没有2型糖尿病的女性中，使用激素替代疗法(MHT)与空腹胰岛素的小幅降低（11项研究：N=4262，平均差异[MD] -5.90 pmol/l [95%置信区间(CI) -8.03, -3.77 pmol/l]；高证据质量）以及胰岛素抵抗的稳态模型评估分数的小幅降低（四项研究：N=2883，MD -0.21 [95% CI -0.32, -0.09]；中等证据质量）有关，与非MHT使用者相比，新发2型糖尿病的风险也较低（14项研究：N=1,450,134，风险比0.83 [95% CI 0.75, 0.92]；非常低的证据质量）。

Among women with type 2 diabetes, MHT was associated with small reductions in fasting plasma glucose (16 studies: N=1379, MD -1.07 mmol/l [95% CI -1.86, -0.28 mmol/l]; very low CoE), haemoglobin A1c (17 studies: N=15,720, MD -5.47 mmol/mol [-0.50%] [95% CI -8.32, -2.62 mmol/mol (-0.76, -0.24%)]; very low CoE), cholesterol (15 studies: N=907, MD -0.37 mmol/l [95% CI -0.50, -0.24 mmol/l]; low CoE), low-density lipoprotein cholesterol (16 studies: N=961, MD -0.33 mmol/l [95% CI -0.54, -0.13 mmol/l]; low CoE) and systolic blood pressure (nine studies: N=630, MD -3.43 mmHg (-0.46 kPa) [95% CI -4.88, -1.98 mmHg]; low CoE), compared with non-MHT users.

在有2型糖尿病的女性中，MHT与空腹血糖的小幅降低（16项研究：N=1379，MD -1.07 mmol/l [95% CI -1.86, -0.28 mmol/l]；非常低的证据质量）、血红蛋白A1c的小幅降低（17项研究：N=15,720，MD -5.47 mmol/mol [-0.50%] [95% CI -8.32, -2.62 mmol/mol (-0.76, -0.24%)]；非常低的证据质量）、胆固醇的小幅降低（15项研究：N=907，MD -0.37 mmol/l [95% CI -0.50, -0.24 mmol/l]；低证据质量）、低密度脂蛋白胆固醇的小幅降低（16项研究：N=961，MD -0.33 mmol/l [95% CI -0.54, -0.13 mmol/l]；低证据质量）和收缩压的小幅降低（九项研究：N=630，MD -3.43 mmHg (-0.46 kPa) [95% CI -4.88, -1.98 mmHg]；低证据质量）有关，与非MHT使用者相比。

conclusions/interpretation

MHT showed small beneficial associations with glucose metabolism among women with and without type 2 diabetes, while the effect size was generally too small to be clinically significant.

MHT在有和没有2型糖尿病的女性中显示出与葡萄糖代谢的小幅有益关联，但效应大小通常太小，不足以具有临床意义。

Future studies are needed to shed more light on the effect of MHT by initiation age.

需要进一步的研究来更深入地了解按开始年龄划分的MHT的效果。

Study limitations include the predominantly single-reviewer screening and assessment, the high risk of bias of the included studies and restricted geographical representation.

研究局限性包括主要是单个审查员的筛选和评估、所包括研究的高偏倚风险以及地理代表性的限制。

registration

The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251230387).

该研究方案已在国际前瞻性系统评价登记处（PROSPERO; CRD420251230387）注册。

funding

This work was supported by a National Health and Medical Research Council investigator grant (APP2009577).

本研究得到了国家健康与医学研究委员会调查员资助（APP2009577）。