Effect of estrogen supplementation therapy on vaginal microbiota and local immunity in postmenopausal women with high-risk HPV infection
10.3760/cma.j.cn101441-20231105-00200
- VernacularTitle: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
- Author:
Xiaosheng XU
1
;
Rong ZHAO
;
Weiwei FENG
;
Jian SHEN
Author Information
1. 上海交通大学医学院附属瑞金医院妇产科，上海 200025
- Publication Type:Journal Article
- Keywords:
Human papillomavirus;
Menopause;
Vaginal microbial
- From:
Chinese Journal of Reproduction and Contraception
2024;44(2):116-122
- CountryChina
- Language:Chinese
-
Abstract:
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.
