Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms

Krystal Thomas-White, Susanne Taege, Roberto Limeira, Cynthia Brincat, Cara Joyce, Evann E. Hilt, Laura Mac-Daniel, Katherine A. Radek, Linda Brubaker, Elizabeth R. Mueller, Alan J. Wolfe

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: 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. Objective: This study aimed to determine if estrogen treatment of postmenopausal women with overactive bladder decreases urobiome diversity. Study Design: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)727.e1-727.e11
JournalAmerican journal of obstetrics and gynecology
Volume223
Issue number5
DOIs
StatePublished - Nov 2020
Externally publishedYes

Bibliographical note

Funding Information:
K.T.W. reports being a member of the advisory board of Live UTI Free. K.A.R. reports receiving research support from Kimberly-Clark Corporation . L.B. reports receiving editorial stipends from the Journal of the American Medical Association, Female Pelvic Medicine and Reconstructive Surgery, and UpToDate. E.R.M. reports receiving research support from Astellas Scientific and Medical Affairs Inc, being a member of the advisory board of the Boston Scientific Corporation , receiving royalties from UpToDate, and performing legal review for Bulter-Snow and Ethicon . A.J.W. reports receiving research support from Astellas Scientific and Medical Affairs Inc and Kimberly-Clark Corporation. S.T., C.B., C.J., E.E.H., and L.M.D. report no conflict of interest.

Funding Information:
K.T.W. reports being a member of the advisory board of Live UTI Free. K.A.R. reports receiving research support from Kimberly-Clark Corporation. L.B. reports receiving editorial stipends from the Journal of the American Medical Association, Female Pelvic Medicine and Reconstructive Surgery, and UpToDate. E.R.M. reports receiving research support from Astellas Scientific and Medical Affairs Inc, being a member of the advisory board of the Boston Scientific Corporation, receiving royalties from UpToDate, and performing legal review for Bulter-Snow and Ethicon. A.J.W. reports receiving research support from Astellas Scientific and Medical Affairs Inc and Kimberly-Clark Corporation. S.T., C.B., C.J., E.E.H., and L.M.D. report no conflict of interest.This study was funded by the Loyola Urogynecology Division Research Fund, an investigator-initiated grant from the Kimberly-Clark Corporation, by 2 National Institutes of Health awards given to A.J.W. and L.B. (R56DK104718 and R01 DK104718), and by the Arthur J. Schmitt Dissertation Fellowship. The funders had no input in the design, execution, or interpretation of the study.

Funding Information:
This study was funded by the Loyola Urogynecology Division Research Fund, an investigator-initiated grant from the Kimberly-Clark Corporation, by 2 National Institutes of Health awards given to A.J.W. and L.B. (R56DK104718 and R01 DK104718), and by the Arthur J. Schmitt Dissertation Fellowship. The funders had no input in the design, execution, or interpretation of the study.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • 16S rRNA gene sequencing
  • antimicrobial peptides
  • enhanced urine culture
  • estrogen
  • overactive bladder
  • urgency urinary incontinence
  • urinary microbiome
  • urinary urgency
  • vaginal microbiome

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