目标:如今,针对雌二醇与阴道炎之间因果关系的孟德尔随机化(MR)研究有限.因此,这项研究进行了一项双向MR研究,以阐明两者之间的因果效应和相关影响因素。
方法:所有遗传数据集均使用基于IEUGWAS数据库中欧洲血统个体的公开汇总统计数据获得。使用MR-Egger进行MR分析,加权中位数(WM)和逆方差加权(IVW)方法评估暴露与结局之间的因果关系,并通过综合评估多效性效应和异常值的影响来验证研究结果。
结果:MR分析显示雌二醇与阴道炎风险之间没有显著的因果关系。雌二醇与初潮年龄呈负相关(IVW,OR:0.9996,95%CI:0.9992-1.0000,P=0.0295;WM,OR:0.9995,95%CI:0.9993-0.9998,P=0.0003),初潮年龄与阴道炎呈正相关(IVW,OR:1.5108,95%CI:1.1474-2.0930,P=0.0043;MR-Egger,OR:2.5575,95%CI:1.7664-9.6580,P=0.0013)。雌二醇与绝经年龄呈负相关(IVW,OR:0.9872,95%CI:0.9786-0.9959,P=0.0041)。然而,绝经年龄与阴道炎之间无因果关系(P>0.05)。此外,HPVE716型,HPVE718型和乳酸杆菌对雌二醇和阴道炎没有直接的因果关系(P>0.05)。敏感性分析显示没有异质性和水平多效性。
结论:当雌激素水平下降时,会导致更晚的初潮,初潮年龄越晚可能会增加阴道炎的风险,强调女性生殖道接受雌激素刺激的时间越长,防御能力越强,阴道炎的患病率降低。总之,这项研究间接支持了雌激素水平降低或雌激素刺激时间短与阴道炎风险增加之间的关联.
OBJECTIVE: Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and
vaginitis. Therefore, this study conducted a two-way MR study to clarify the causal effect and related influencing factors between them.
METHODS: All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR-Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers.
RESULTS: MR analysis revealed no significant causal relationship between estradiol and
vaginitis risk. There was a negative correlation between estradiol and age at menarche (IVW, OR: 0.9996, 95% CI: 0.9992-1.0000, P = 0.0295; WM, OR: 0.9995, 95% CI: 0.9993-0.9998, P = 0.0003), and there was a positive correlation between age at menarche and
vaginitis (IVW, OR: 1.5108, 95% CI: 1.1474-2.0930, P = 0.0043; MR-Egger, OR: 2.5575, 95% CI: 1.7664-9.6580, P = 0.0013). Estradiol was negatively correlated with age at menopause (IVW, OR: 0.9872, 95% CI: 0.9786-0.9959, P = 0.0041). However, there was no causal relationship between age at menopause and
vaginitis (P > 0.05). In addition, HPV E7 Type 16, HPV E7 Type 18, and Lactobacillus had no direct causal effects on estradiol and vaginitis (P > 0.05). Sensitivity analyses revealed no heterogeneity and horizontal pleiotropy.
CONCLUSIONS: When estrogen levels drop, it will lead to a later age of menarche, and a later age of menarche may increase the risk of
vaginitis, highlighting that the longer the female reproductive tract receives estrogen stimulation, the stronger the defense ability is formed, and the prevalence of vaginitis is reduced. In conclusion, this study indirectly supports an association between reduced level of estrogen or short time of estrogen stimulation and increased risk of vaginitis.