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Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy

Brotman, Rebecca M. PhD, MPH1,2; Shardell, Michelle D. PhD2; Gajer, Pawel PhD1; Fadrosh, Doug MS1; Chang, Kathryn RN3; Silver, Michelle I. ScM3; Viscidi, Raphael P. MD4; Burke, Anne E. MD, MPH5; Ravel, Jacques PhD1,6; Gravitt, Patti E. PhD, MS3

doi: 10.1097/GME.0b013e3182a4690b
Original Articles

Objective The vaginal microbiota helps protect the female genital tract from disease. We sought to describe the composition of the vaginal microbiota in premenopausal, perimenopausal, and postmenopausal women and to explore the association between the microbiota and vulvovaginal atrophy (VVA).

Methods Eighty-seven women (aged 35-60 y) were classified as premenopausal (n = 30), perimenopausal (n = 29), or postmenopausal (n = 28) according to Stages of Reproductive Aging Workshop guidelines. Midvaginal bacterial community composition was characterized by 16S ribosomal RNA gene analysis.

Results Bacterial communities clustered into six community state types (CSTs), of which four were dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, or Lactobacillus jensenii, and two (CST IV-A and CST IV-B) had low relative abundance of Lactobacillus. CST IV-A was characterized by Streptococcus and Prevotella, whereas CST IV-B was characterized by Atopobium. There were significant associations between menopause stage and CST (P = 0.004) and between VVA and CST (P = 0.002). Perimenopausal women were more likely to be classified as CST IV-A or L. gasseri CST, whereas postmenopausal women were often classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more prevalent in premenopausal women. Nineteen participants had signs of mild or moderate VVA. Compared with women with no VVA, the vaginal microbiota of women with mild or moderate atrophy had 25-fold greater odds of being classified as CST IV-A versus L. crispatus CST (adjusted odds ratio, 25.89; 95% credible interval, 2.98-406.79).

Conclusions A distinct bacterial community state (CST IV-A) with a low relative abundance of Lactobacillus is associated with VVA. Future studies recruiting a larger number of women are needed to replicate the findings. This study provides an impetus for future longitudinal studies designed to manage, modulate, and restore vaginal microbiota homeostasis, which would provide stronger evidence for a causal relationship with VVA and ultimately improve the treatment and prevention of atrophic vaginitis in menopause.

From the 1Institute for Genome Sciences and 2Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Departments of 4Pediatrics and Neurovirology and 5Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, MD; and 6Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD.

Received May 17, 2013; revised and accepted July 10, 2013.

Bacterial 16S ribosomal RNA gene sequences were deposited at the National Center for Biotechnology Information Short Read Archive (Short Read Archive accession number SRA090069; study accession number SRP025158).

Funding/support: This study was supported by National Institutes of Health grants K01-AI080974 (R.M.B.), K25-AG034216 (M.D.S.), U01-AI070921 (J.R.), UH2-AI083264 (J.R.), and R01-CA123467 (P.E.G.).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Rebecca M. Brotman, PhD, MPH, Institute for Genome Sciences and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Room 633, 801 West Baltimore Street, Baltimore, MD 21201. E-mail:

© 2014 by The North American Menopause Society.