Li Xiaofeng, Fang Zhuofan, Yang Xin, Pan Huijuan, Zhang Chunfang, Li Xiaoling, Bai Yan, Wang Fang
Reproductive Medicine Center, Lanzhou University Second Hospital, Lanzhou City, P.R. China.
The Second Clinical Medical College of Lanzhou University, Lanzhou City, P.R. China.
J Obstet Gynaecol Res. 2021 May;47(5):1804-1816. doi: 10.1111/jog.14725. Epub 2021 Mar 1.
Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients.
The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language.
Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] -1.33; 95% confidence interval [CI] -2.16 to -0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD -1.82; 95% CI -2.56 to -1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI -0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD -2.05; 95% CI -2.40 to -1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI -1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI -22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001).
Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.
二甲双胍作为胰岛素增敏剂在多囊卵巢综合征（PCOS）患者中广泛应用。然而，既往研究发现二甲双胍对PCOS患者同型半胱氨酸水平的影响并不一致。本综述的目的是分析二甲双胍对PCOS患者同型半胱氨酸水平的影响。
根据预定义的检索词检索Cochrane图书馆、Pubmed和科学网。对发表时间和语言无限制。
纳入11项研究并提取数据。PCOS患者服用二甲双胍后同型半胱氨酸水平显著升高（平均差值[MD]-1.33；95%置信区间[CI]-2.16至-0.49，p=0.002）。亚组分析显示，体重指数（BMI）≥25的PCOS患者单独服用二甲双胍后同型半胱氨酸水平普遍升高（MD-1.82；95%CI-2.56至-1.07，p<0.00001）。BMI<25的PCOS患者同型半胱氨酸水平无显著变化（MD0.69；95%CI-0.41至1.79，p=0.22）。亚组分析显示，服用二甲双胍>3个月或服用二甲双胍≤3个月时无显著差异（p=0.84）。PCOS患者服用二甲双胍≥1700mg/天显著升高同型半胱氨酸水平（MD-2.05；95%CI-2.40至-1.70，p<***0.00001）。当服用二甲双胍<1700mg/天时，PCOS患者同型半胱氨酸水平无显著差异（MD0.15；95%CI-1.06至1.37，p=0.80）。两个亚组之间的差异显著（p=0.0006）。二甲双胍治疗前后维生素B12水平无显著差异（MD24.70；95%CI-22.54至71.93，p=0.31）。服用二甲双胍后血清叶酸水平降低（MD1.03；95%CI0.80至1.26，p<0.00001）。
单独服用二甲双胍会使未孕PCOS患者的同型半胱氨酸水平升高，叶酸水平降低。并且，建议二甲双胍的剂量应小于1700mg/天。在未孕PCOS患者服用二甲双胍期间补充叶酸和B族维生素可能至关重要。我们应高度关注二甲双胍对PCOS患者的潜在影响。
