首页|雌激素补充治疗对绝经后高危型HPV感染女性阴道菌群及局部免疫的影响

雌激素补充治疗对绝经后高危型HPV感染女性阴道菌群及局部免疫的影响

扫码查看
目的 探讨雌激素补充治疗对绝经后高危型人乳头瘤病毒(human papillomavirus,HPV)感染女性阴道菌群及局部免疫的影响.方法 2018年6月至2023年6月期间在上海市瑞金康复医院妇科招募体检或因妇科疾病就诊的74例绝经后女性为研究对象.根据HPV检测结果分为高危型HPV阴性女性(正常组,n=14)和高危型HPV阳性女性(n=60).采用随机对照试验,将高危型HPV阳性女性利用随机数字表法分为试验组(高危型HPV阳性且口服低剂量雌激素治疗,n=30)和对照组(高危型HPV阳性且未口服低剂量雌激素,n=30).在入组时(即第0周)、入组后第4周和第8周采用荧光定量PCR仪和酶联免疫吸附实验检测3组的阴道微生物群落结构以及阴道灌洗液中的炎症细胞因子表达情况.结果 入组时3 组患者年龄、绝经时间、体质量指数、收缩压、舒张压、心率、pH值和阴道细胞成熟指数(vaginal cell maturation index,VMI)差异均无统计学意义(均P>0.05),基线可比.经雌激素治疗后,试验组第4周(5.27±0.13)和第8周(4.84±0.15)的pH值均显著低于第0周(6.59±0.17,均P<0.001),而试验组第4周(41.62±2.62)和第8周的VMI(58.28±2.16)均显著高于第0周(25.97±2.60,均P<0.001).定量结果表明正常组、试验组、对照组3组间及各自组内(即每组不同检测时间点)的大肠杆菌(Escherichia coli)丰度差异均无统计学意义(均P>0.05).试验组第0周加德纳菌(Gardnerella)和奇异菌属(Atopobium)丰度显著高于第4周和第8周(均P<0.001).但经雌激素治疗后第4周的试验组阴道Gardnerella和Atopobium丰度显著低于对照组(均P<0.001),和正常组相比差异均无统计学意义(均P>0.05).第0、第4、第8周的正常组、试验组和对照组组间的普雷沃氏菌属(Prevotella)、加氏乳酸杆菌(L.Gasseri)和惰性乳酸杆菌(L.Iners)丰度差异均无统计学意义(均P>0.05).第0周试验组和对照组卷曲乳酸杆菌(L.Crispatus)和詹氏乳酸杆菌(L.Jensenii)丰度均显著低于正常组(均P<0.001).第4周和第8周试验组的L.Crispatus丰度均显著高于对照组(均P<0.001),和正常组比较差异均无统计学意义(均P>0.05).正常组、试验组和对照组女性阴道灌洗液中的白细胞介素(interleukin,IL)-6、IL-8和干扰素(interferon,IFN)-α浓度差异均无统计学意义(均P>0.05).试验组和对照组中IL-1β浓度均显著高于正常组(均P<0.001),试验组和对照组间差异无统计学意义(P>0.05).试验组第8周肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)浓度显著低于第0周(P<0.001),而第4周后TNF-α浓度与第0周差异无统计学意义(P>0.05).与试验组第0周相比,经雌激素治疗4周后,趋化因子C-X-C motif 配体14、IFN-β浓度差异无统计学意义(均P>0.05),而治疗8周后这两个因子水平显著下降(均P<0.001).与正常组相比,试验组和对照组IFN-γ诱导蛋白16浓度明显升高(均P<0.001),试验组和对照组组间差异无统计学意义(P>0.05).结论 HPV感染后会增加绝经后妇女阴道中Gardnerella和Atopobium的丰度并降低L.Crispatus和 L.Jensenii的丰度,进一步破坏阴道微环境中微生物的稳态.雌激素补充治疗对绝经后高危型HPV感染女性的阴道菌群和局部免疫有一定的改善作用.
Effect of estrogen supplementation therapy on vaginal microbiota and local immunity in postmenopausal women with high-risk HPV infection
Objective To investigate the effect of estrogen supplementation therapy on vaginal microbiota and local immunity of postmenopausal high-risk human papillomavirus(HPV)infected women.Methods A total of 74 postmenopausal women who underwent gynecological examinations or visits at Department of Gynecology,Shanghai Ruijin Rehabilitation Hospital from June 2018 to June 2023 were included in this study.According to HPV test,they were divided into the high-risk HPV-negative women(normal group,n=14)and the high-risk HPV-positive women(n=60).A randomized controlled clinical trial was designed.Within the high-risk HPV-positive women,they were further randomly assigned by using the random number table method to the experimental group(high-risk HPV-positive women receiving low-dose estrogen therapy orally,n=30)and control group(high-risk HPV-positive women not receiving low-dose estrogen therapy,n=30).Vaginal microbiota composition and expression of inflammatory cytokines in vaginal lavage fluid were measured using fluorescence quantitative PCR and enzyme-linked immunosorbent assay at baseline(week 0),4th week,and 8th week after enrollment.Results There were no significant differences in age,menopausal time,body mass index,systolic pressure,diastolic pressure,heart rate,pH value and vaginal cell maturation index(VMI)among the normal group,the experimental group and control group(all P>0.05)which indicated the baseline was comparable.After estrogen treatment,the pH value of the experimental group at 4th and 8th weeks(5.27±0.13,4.84±0.15)was significantly lower than that at week 0(6.59±0.17,all P<0.001),while the vaginal cell maturation index(VMI)at 4th and 8th weeks(41.62±2.62,58.28±2.16)was significantly higher than that at week 0(25.97±2.60,all P<0.001).The quantitative results showed no significant differences in the abundance of Escherichia coli among the normal group,the experimental group,and control group,and within each group at different time points(all P>0.05).The abundance of Gardnerella and Atopobium in the experimental group was significantly higher at week 0 compared with 4th week and 8th week(all P<0.001).However,after estrogen treatment,the abundance of Gardnerella and Atopobium in the experimental group at 4th week was significantly lower than those in control group(all P<0.001),with no significant difference compared with the normal group(all P>0.05).There were no significant differences in the abundance of Prevotella,L.Gasseri,and L.Iners among the normal group,the experimental group,and control group at week 0,4th week and 8th week(all P>0.05).The abundance of L.Crispatus and L.Jensenii in the experimental group and control group at week 0 was significantly lower than that in the normal group(all P<0.001).The abundance of L.Crispatus in the experimental group at 4th week and 8th week was significantly higher than that in control group(all P<0.001),with no significant difference compared with the normal group(P>0.05).There were no significant differences in the concentrations of interleukin(IL)-6,IL-8,and interferon(IFN)-α in vaginal lavage fluid among the normal group,the experimental group,and control group(all P>0.05).The concentration of IL-1β in the experimental group and control group was significantly higher than that in the normal group(P<0.001),with no significant difference between the experimental group and control group(P>0.05).The concentration of tumor necrosis factor alpha(TNF-α)in the experimental group at 8th week was significantly lower than that at week 0(P<0.001),while there was no significant difference in TNF-α concentration after week 4 compared with week 0(P>0.05).Compared with the experimental group at week 0,the concentration of chemokine C-X-C motif ligand 14(CXCL14)and IFN-β significantly decreased after 8 weeks of estrogen treatment(all P<0.001),with no significant change after 4 weeks of treatment(P>0.05).Compared with the normal group,the concentration of IFN-γ inducible protein 16 in the experimental group and control group significantly increased(all P<0.001),with no significant difference between the experimental group and control group(P>0.05).Conclusion HPV infection can increase the abundance of Gardnerella and Atopobium in the vagina of postmenopausal women and decrease the abundance of L.Crispatus and L.Jensenii,which further disrupts the homeostasis of microorganisms in the vaginal microenvironment.Estrogen replacement therapy has a certain improvement effect on vaginal flora and local immunity in postmenopausal women with high-risk HPV infection.

Human papillomavirusMenopauseVaginal microbial

许啸声、赵荣、冯炜炜、沈健

展开 >

上海交通大学医学院附属瑞金医院妇产科,上海 200025

上海市瑞金康复医院妇科,上海 200023

人乳头瘤病毒 绝经 阴道内微生物群落

上海市自然科学基金

18ZR1423900

2024

中华生殖与避孕杂志
上海计划生育科学研究所

中华生殖与避孕杂志

CSTPCD北大核心
影响因子:0.989
ISSN:2096-2916
年,卷(期):2024.44(2)
  • 27