Elsevier

Maturitas

Volume 91, September 2016, Pages 42-50
Maturitas

Review article
Menopause and the vaginal microbiome

https://doi.org/10.1016/j.maturitas.2016.05.015Get rights and content

Highlights

  • Vaginal lactobacilli are strongly associated with vaginal health in menopause.

  • Disruption in the vaginal microbiome correlates with vaginal symptoms of menopause.

  • Lactobacilli decrease along with menopause-related hormonal and epithelial changes.

  • Hormone replacement therapy can restore vaginal lactobacilli following menopause.

  • Probiotic therapies show promise in reinstating vaginal homeostasis in menopause.

Abstract

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis.

Introduction

Researchers have been investigating bacteria that inhabit the vaginal cavity since the 1800s. Early scientists used light microscopy and Gram staining to study the microbial composition of the vaginal environment. As technology progressed, bacterial culturing techniques and PCR were developed and researchers were able to more accurately identify bacterial species that are present in the vagina. Currently, 16S rRNA sequencing provides a culture-independent method to identify the vaginal microbiota [1]. Next-generation sequencing can be used effectively to characterize a large array of taxonomic species that would not be possible with other methods

An environment rich in Lactobacillus species is associated with vaginal health [2]. Although other anaerobic and aerobic bacteria colonize the vagina, Lactobacillus is the dominant species in most women [1], [2]. Lactobacillus spp. produce compounds such as hydrogen peroxide and lactic acid that have antimicrobial properties [3]. The resulting microenvironment is critically important in preventing colonization of the vagina by diverse, anaerobic and microaerophilic pathogens, which can result in depletion of lactobacilli and dysbiosis (imbalance of vaginal community) called bacterial vaginosis (BV) [4]. BV has been associated with an array of poor obstetric and gynecologic health outcomes in both pre- and postmenopausal women [1], [4], [5], [6]. Particularly relevant to postmenopausal women, disruptions in the vaginal microbiota affect vulnerability to gynecologic infections and sexually transmitted infections (STI) [4], [7], [8], [9].

Multiple studies have focused on the vaginal microbiota in healthy, reproductive-aged women and recent sequence-based studies have begun to elucidate the dominant vaginal community states in menopausal women (Table 1). A plethora of changes take place during menopause that affect both the microanatomical structure and microbiome of the lower female reproductive tract [10]. Local, vaginal symptoms include vaginal dryness, vaginal atrophy, and dyspareunia can negatively impact a woman’s quality of life [10].

The objective of this review it to compare the changes that have been identified in the vaginal microbiome of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms and sexual health and quality of life, and conclude with the potential of probiotics to reinstate vaginal homeostasis following menopause.

Section snippets

Methods

A search of the scientific literature was conducted using PubMed/Medline using the following search terms “vaginal microbiota and menopause”, “vaginal microbiome and menopause”, “vaginal flora and menopause”, “vaginal bacteria and menopause”, “vaginal atrophy and menopause”, and “vulvovaginal atrophy and the vaginal microbiota”. Pertinent original articles and reviews that were peer-reviewed, indexed in PubMed/Medline and written in English were included. The publication dates were not limited

Characterization of the vaginal microbiome in menopause

Early studies investigating the bacterial composition of the vagina used cytology and Gram staining techniques. Coupled with the use of bacterial culture techniques, researchers found that vaginal lactobacilli, yeasts and BV were less common in postmenopausal women compared to premenopausal women [11], [12], [13]. In postmenopausal women on hormone replacement therapy (HRT), there was a strong association with the level of Lactobacillus colonization [12], [13]. According to Cauci et al., 44.1%

Conclusions

Research regarding the vaginal microbiome and menopause has evolved over the last decade. Light microscopy and culture techniques revealed healthy vaginal microbiomes are dominated by Lactobacillus species. Next- generation sequencing technology has allowed scientists to further categorize and understand the complexity and diversity of species that inhabit the vaginal cavity. Overall, Lactobacillus dominance is strongly correlated to vaginal health and homeostasis in both pre- and

Contributors

MMH-K designed the scope and organization of the review.

ALM and MMH-K conducted literature reviews, data extraction and analysis, figure and table construction and contributed to the writing of the manuscript.

MMH-K supervised the writing and critically edited and reviewed the complete manuscript, table and figure.

Both authors approved the final manuscript for submission.

Conflict of interest

The authors declare no conflict of interest.

Funding

This work was supported by the University of Arizona.

Provenance and peer review

This article has undergone peer review.

Acknowledgement

The authors would like to thank the members of the Herbst-Kralovetz research team for thoughtful discussions on this topic.

References (56)

  • D. Chase et al.

    The vaginal and gastrointestinal microbiomes in gynecologic cancers: a review of applications in etiology, symptoms and treatment

    Gynecol. Oncol.

    (2015)
  • V. Redondo-Lopez et al.

    Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora

    Rev. Infect. Dis.

    (1990)
  • D.E. O'Hanlon et al.

    Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota

    PLoS One

    (2013)
  • J.M. Marrazzo

    A persistent(ly) enigmatic ecological mystery: bacterial vaginosis

    J. Infect. Dis.

    (2006)
  • B. Ma et al.

    Vaginal microbiome: rethinking health and disease

    Annu. Rev. Microbiol.

    (2012)
  • S.L. Hillier et al.

    Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The vaginal infections and prematurity study group

    N. Engl. J. Med.

    (1995)
  • R. Raz et al.

    A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections

    N. Engl. J. Med.

    (1993)
  • O. Drew et al.

    Sexually transmitted infections in the older woman

    Menopause Int.

    (2008)
  • H.L. Martin et al.

    Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition

    J. Infect. Dis.

    (1999)
  • M. Farage et al.

    Lifetime changes in the vulva and vagina

    Arch. Gynecol. Obstet.

    (2006)
  • S.L. Hillier et al.

    Vaginal microflora in postmenopausal women who have not received estrogen replacement therapy

    Clin. Infect. Dis.

    (1997)
  • S. Cauci et al.

    Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women

    J. Clin. Microbiol.

    (2002)
  • W.L. Pabich et al.

    Prevalence and determinants of vaginal flora alterations in postmenopausal women

    J. Infect. Dis.

    (2003)
  • J.P. Burton et al.

    Evaluation of the bacterial vaginal flora of 20 postmenopausal women by direct (Nugent score) and molecular (polymerase chain reaction and denaturing gradient gel electrophoresis) techniques

    J. Infect. Dis.

    (2002)
  • J. Ravel et al.

    Vaginal microbiome of reproductive-age women

    Proc. Natl. Acad. Sci. U. S. A.

    (2011)
  • P. Gajer et al.

    Temporal dynamics of the human vaginal microbiota

    Sci. Transl. Med.

    (2012)
  • S. Srinivasan et al.

    Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis

    PLoS One

    (2010)
  • J.G. Bartlett et al.

    Quantitative bacteriology of the vaginal flora

    J. Infect. Dis.

    (1977)
  • Cited by (200)

    View all citing articles on Scopus
    View full text