Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA.
Obstetrics and Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL; Mount Carmel Medical Group, Mount Carmel Urogynecology and Pelvic Floor, Westerville, OH.
Am J Obstet Gynecol. 2020 Nov;223(5):727.e1-727.e11. doi: 10.1016/j.ajog.2020.08.006. Epub 2020 Aug 11.
Previous work has shown that the vaginal microbiome decreases in Lactobacillus predominance and becomes more diverse after menopause. It has also been shown that estrogen therapy restores Lactobacillus dominance in the vagina and that topical estrogen is associated with overactive bladder symptom improvement. We now know that the bladder contains a unique microbiome and that increased bladder microbiome diversity is associated with overactive bladder. However, there is no understanding of how quickly each pelvic floor microbiome responds to estrogen or if those changes are associated with symptom improvement.
This study aimed to determine if estrogen treatment of postmenopausal women with overactive bladder decreases urobiome diversity.
We analyzed data from postmenopausal participants in 2 trials (NCT02524769 and NCT02835846) who chose vaginal estrogen as the primary overactive bladder treatment and used 0.5 g of conjugated estrogen (Premarin cream; Pfizer, New York City, NY) twice weekly for 12 weeks. Baseline and 12-week follow-up data included the Overactive Bladder questionnaire, and participants provided urine samples via catheter, vaginal swabs, perineal swabs, and voided urine samples. Microbes were detected by an enhanced culture protocol. Linear mixed models were used to estimate microbiome changes over time. Urinary antimicrobial peptide activity was assessed by a bacterial growth inhibition assay and correlated with relative abundance of members of the urobiome.
In this study, 12 weeks of estrogen treatment resulted in decreased microbial diversity within the vagina (Shannon, P=.047; Richness, P=.043) but not in the other niches. A significant increase in Lactobacillus was detected in the bladder (P=.037) but not in the vagina (P=.33), perineum (P=.56), or voided urine (P=.28). The change in Lactobacillus levels in the bladder was associated with modest changes in urgency incontinence symptoms (P=.02). The relative abundance of the genus Corynebacterium correlated positively with urinary antimicrobial peptide activity after estrogen treatment.
Estrogen therapy may change the microbiome of different pelvic floor niches. The vagina begins to decrease in diversity, and the bladder experiences a significant increase in Lactobacillus levels; the latter is correlated with a modest improvement in the symptom severity subscale of the Overactive Bladder questionnaire.
先前的研究表明,阴道微生物组中乳杆菌的优势减少,绝经后变得更加多样化。研究还表明,雌激素治疗可恢复阴道中的乳杆菌优势,局部雌激素与膀胱过度活动症症状改善有关。我们现在知道膀胱中存在独特的微生物组,并且膀胱微生物组多样性增加与膀胱过度活动症有关。但是,我们尚不清楚每个盆底微生物组对雌激素的反应速度有多快,或者这些变化是否与症状改善有关。
本研究旨在确定雌激素治疗绝经后膀胱过度活动症患者是否会降低泌尿微生物组的多样性。
我们分析了来自 2 项试验(NCT02524769 和 NCT02835846)的绝经后参与者的数据,这些参与者选择阴道雌激素作为主要的膀胱过度活动症治疗方法,每周两次使用 0.5 g 的结合雌激素(Premarin 乳膏;辉瑞公司,纽约市,NY)治疗 12 周。基线和 12 周随访数据包括膀胱过度活动症问卷,参与者通过导管、阴道拭子、会阴拭子和排尿尿液样本提供尿液样本。通过增强培养方案检测微生物。线性混合模型用于估计随时间的微生物组变化。通过细菌生长抑制测定法评估尿抗菌肽活性,并与泌尿微生物组成员的相对丰度相关联。
在这项研究中,雌激素治疗 12 周导致阴道内微生物多样性降低(Shannon,P=.047;Richness,P=.043),但其他部位没有。膀胱中乳杆菌的显著增加(P=.037)而不是阴道(P=.33)、会阴(P=.56)或排尿尿液(P=.28)。膀胱中乳杆菌水平的变化与尿急失禁症状的适度变化相关(P=.02)。雌激素治疗后,棒状杆菌属的相对丰度与尿抗菌肽活性呈正相关。
雌激素治疗可能会改变不同盆底部位的微生物组。阴道开始减少多样性,而膀胱中乳杆菌水平显著增加;后者与膀胱过度活动症问卷的症状严重程度亚量表的适度改善相关。