DataSheet_4_The influence of 17β-estradiol plus norethisterone acetate treatment on markers of glucose and insulin metabolism in women: a systematic review and meta-analysis of randomized controlled trials.docx

ObjectiveDespite the fact that some evidence suggests that the administration of 17β-estradiol plus norethisterone acetate influences glucose and insulin metabolism in women, these findings are still contradictory. Thus, we aimed to examine the impact of the co-administration of 17β-estradiol and norethisterone acetate on glycated haemoglobin (HbA1c), fasting glucose, insulin and C-peptide concentrations in females by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).
MethodsWe searched four databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) using specific keywords and word combinations. The random-effects model (DerSimonian and Laird model) was employed to compute the weighted mean difference (WMD) and 95% confidence intervals (CIs) for the variations from baseline of HbA1c, fasting glucose, insulin, and C-peptide concentrations.
ResultsIn total, 14 RCTs were entered into the quantitative synthesis. The combined administration of 17β-estradiol and norethisterone acetate decreased HbA1c (WMD: -0.65%, 95% CI: -1.15 to -0.15; P=0.011), fasting glucose (WMD: -11.05 mg/dL, 95% CI: -16.6 to -5.5; P<0.001) and insulin (WMD: -1.35 mIU/L, 95% CI: -2.20 to -0.50; P=0.001) levels. C-peptide concentrations’ declined only in females diagnosed with overweight/obesity or diabetes.
ConclusionEvidence to date points out that the administration of 17β-estradiol and norethisterone acetate has a positive impact on glucose metabolism in women by reducing fasting glucose, HbA1c, and insulin values. Future studies need to confirm the potential benefits of this drug combination in the prevention and/or management of cardiometabolic disorders.

研究目的：尽管已有部分研究表明，联合施用17β-雌二醇（17β-estradiol）与醋酸炔诺酮（norethisterone acetate）会对女性的葡萄糖与胰岛素代谢产生影响，但相关研究结论仍存在争议。因此，本研究旨在通过对随机对照试验（randomized controlled trials, RCTs）进行系统评价与荟萃分析，探讨该联合用药方案对女性糖化血红蛋白（glycated haemoglobin, HbA1c）、空腹血糖、胰岛素及C肽浓度的影响。
研究方法：本研究通过特定关键词及词组组合，检索了PubMed/MEDLINE、Scopus、Embase及Web of Science共4个数据库。采用随机效应模型（DerSimonian与Laird模型），计算糖化血红蛋白、空腹血糖、胰岛素及C肽浓度相较于基线的变化值的加权均数差（weighted mean difference, WMD）与95%置信区间（confidence intervals, CIs）。
研究结果：最终共有14项随机对照试验被纳入定量合成分析。联合施用17β-雌二醇与醋酸炔诺酮可降低女性的糖化血红蛋白（加权均数差：-0.65%，95%置信区间：-1.15~-0.15；P=0.011）、空腹血糖（加权均数差：-11.05 mg/dL，95%置信区间：-16.6~-5.5；P<0.001）及胰岛素水平（加权均数差：-1.35 mIU/L，95%置信区间：-2.20~-0.50；P=0.001）。仅在超重/肥胖或确诊糖尿病的女性群体中，C肽浓度出现显著下降。
研究结论：现有研究证据表明，联合施用17β-雌二醇与醋酸炔诺酮可通过降低空腹血糖、糖化血红蛋白及胰岛素水平，对女性的葡萄糖代谢产生积极影响。未来仍需开展相关研究，以验证该药物联合方案在预防和/或管理心脏代谢紊乱方面的潜在益处。