Abstract

After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to the loss of estrogen. An understudied aspect of vaginal health in women who experience dryness due to atrophy is the role of the resident microbes. It is known that the microbiota has an important role in healthy vaginal homeostasis, including maintaining the pH balance and excluding pathogens. The objectives of this study were twofold: first to identify the microbiome of post-menopausal women with and without vaginal dryness and symptoms of atrophy; and secondly to examine any differences in epithelial gene expression associated with atrophy. The vaginal microbiome of 32 post-menopausal women was profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Sixteen subjects were selected for follow-up sampling every two weeks for 10 weeks. In addition, 10 epithelial RNA samples (6 healthy and 4 experiencing vaginal dryness) were acquired for gene expression analysis by Affymetrix Human Gene array. The microbiota abundance profiles were relatively stable over 10 weeks compared to previously published data on premenopausal women. There was an inverse correlation between Lactobacillus ratio and dryness and an increased bacterial diversity in women experiencing moderate to severe vaginal dryness. In healthy participants, Lactobacillus iners and L. crispatus were generally the most abundant, countering the long-held view that lactobacilli are absent or depleted in menopause. Vaginal dryness and atrophy were associated with down-regulation of human genes involved in maintenance of epithelial structure and barrier function, while those associated with inflammation were up-regulated consistent with the adverse clinical presentation.

Highlights

  • The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse [1]

  • A lactobacilli-dominated vaginal microbiota is associated with retention of health, but with menopause it has long been assumed that estrogen replacement therapy (ERT) is required to maintain the dominant lactobacilli and reduce the risk of infection [5]

  • This is supported by studies of the vaginal microbiota using denaturing gel electrophoresis [6,7]

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Summary

Introduction

The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse [1]. These symptoms affect 25–50% post-menopausal women [2,3] and significantly impact their quality of life. A lactobacilli-dominated vaginal microbiota is associated with retention of health, but with menopause it has long been assumed that ERT is required to maintain the dominant lactobacilli and reduce the risk of infection [5] This is supported by studies of the vaginal microbiota using denaturing gel electrophoresis [6,7]. Nextgeneration deep sequencing provides a means to uncover the extent of bacterial presence in a given niche, including the vagina [8,9,10]

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