Department of Otolaryngology Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
Eur J Obstet Gynecol Reprod Biol. 2019 Jun;237:33-41. doi: 10.1016/j.ejogrb.2019.03.029. Epub 2019 Apr 15.
Recently, metformin, first-line drug for type 2 diabetes, has been reported to treat some gynecological tumors. However, these epidemiological studies have never been formally summarized. Considering a single study may lack the power to provide reliable conclusion, we performed two meta-analyses with different indicators to assess metformin's role in reducing the risk of gynecological cancers.
A systematic literature search was carried out in PubMed, Medline (Ovid), Embase database (last search was performed on August 15, 2018). The relative risk (RR) along with a random-effects model were performed on Revman 5.3 and STATA 15.1 for risks analyzing.
A total of 1,710,080 patients in 7 studies were included in first meta-analysis. The results suggested metformin may reduce the risk of gynecological cancers (RR=0.49, 95%CI=0.29-0.82, and p=0.006). In the subgroup analyses: significantly decreased risks were found among Asians (RR=0.27, 95%CI=0.17-0.41, and p<0.00001), ovarian cancer (RR=0.18, 95%CI=0.12-0.28, and p<0.00001), and cervical cancer (RR=0.60, 95%CI=0.43-0.83, and p=0.002), but not in Caucasians (RR=0.81, 95%CI=0.50-1.32, and p=0.40) or in endometrial cancer (RR=0.71, 95%CI=0.29-1.74, and p=0.45). Meanwhile, another total of 8,335,332 cumulative follow-up years, person years, were conducted in 8 studies. The results indicated no statistical significance in general (RR=0.59, 95%CI=0.32-1.10, p=0.10), and no difference in Caucasians (RR=1.15, 95%CI=0.88-1.48, and p=0.30), endometrial cancer (RR=0.89, 95%CI=0.27-2.95, and p=0.84) or ovarian cancer (RR=0.37, 95%CI=0.09-1.49, and p=0.16) when performing subgroup analyses. However, in the subgroup analyses, results in Asians (RR=0.26, 95%CI=0.17-0.40, and p<0.00001) and cervical cancer (RR=0.56, 95%CI=0.40-0.78, and p=0.0005) had an apparent significance.
The results suggested the metformin can be used as a potential anticarcinogenic drug for gynecological cancers' prevention, especially for Asians and cervical cancer. The question remains, still, whether metformin is beneficial for ovarian cancer. Also, we don't know whether it is worth to give metformin to non-diabetes to prevent gynecological cancer.
最近，二甲双胍作为 2 型糖尿病的一线药物，已被报道可用于治疗一些妇科肿瘤。然而，这些流行病学研究从未被正式总结过。由于单一研究可能缺乏提供可靠结论的能力，我们进行了两项荟萃分析，使用不同的指标来评估二甲双胍在降低妇科癌症风险中的作用。
在 PubMed、Medline（Ovid）和 Embase 数据库中进行了系统的文献检索（最后一次搜索是在 2018 年 8 月 15 日进行的）。使用 Revman 5.3 和 STATA 15.1 进行风险分析，采用随机效应模型计算相对风险（RR）。
共有 7 项研究的 171 万患者纳入了第一项荟萃分析。结果表明，二甲双胍可能降低妇科癌症的风险（RR=0.49，95%CI=0.29-0.82，p=0.006）。在亚组分析中：在亚洲人群中发现风险显著降低（RR=0.27，95%CI=0.17-0.41，p<0.00001），卵巢癌（RR=0.18，95%CI=0.12-0.28，p<0.00001）和宫颈癌（RR=0.60，95%CI=0.43-0.83，p=0.002），但在高加索人群中（RR=0.81，95%CI=0.50-1.32，p=0.40）或子宫内膜癌中（RR=0.71，95%CI=0.29-1.74，p=0.45）无统计学意义。同时，在 8 项研究中进行了总共 8335332 年的累积随访、人年。结果表明，总体上无统计学意义（RR=0.59，95%CI=0.32-1.10，p=0.10），在高加索人群中无差异（RR=1.15，95%CI=0.88-1.48，p=0.30）、子宫内膜癌（RR=0.89，95%CI=0.27-2.95，p=0.84）或卵巢癌（RR=0.37，95%CI=0.09-1.49，p=0.16）。然而，在亚组分析中，亚洲人群（RR=0.26，95%CI=0.17-0.40，p<0.00001）和宫颈癌（RR=0.56，95%CI=0.40-0.78，p=0.0005）的结果有明显意义。
结果表明，二甲双胍可作为预防妇科癌症的潜在抗癌药物，特别是对亚洲人和宫颈癌患者。然而，二甲双胍是否对卵巢癌有益，以及是否值得将二甲双胍用于非糖尿病患者以预防妇科癌症，仍存在疑问。
