Background
Vulvodynia (idiopathic vulvar pain) affects up to 8% of women by age 40 years, has
a poorly understood etiology, and has variable treatment efficacy. Several risk factors
are associated with vulvodynia from a history of yeast infections to depression and
allergies. Recent work suggests an altered immune inflammatory mechanism plays a role
in vulvodynia pathophysiology. Because the vaginal microbiome plays an important role
in local immune-inflammatory responses, we evaluated the vaginal microbiome among
women with vulvodynia compared with controls as 1 component of the immune system.
Objective
The objective of the study was to characterize the vaginal microbiome in women with
clinically confirmed vulvodynia and age-matched controls and assess its overall association
with vulvodynia and how it may serve to modify other factors that are associated with
vulvodynia as well.
Study Design
We conducted a case-control study of 234 Minneapolis/Saint Paul–area women with clinically
confirmed vulvodynia and 234 age-matched controls clinically confirmed with no history
of vulvar pain. All participants provided vulvovaginal swab samples for culture-based
and non-culture (sequencing)–based microbiological assessments, background and medical
history questionnaires on demographic characteristics, sexual and reproductive history,
and history of psychosocial factors. Vaginal microbiome diversity was assessed using
the Shannon alpha diversity Index. Data were analyzed using logistic regression.
Results
Culture and molecular-based analyses of the vaginal microbiome showed few differences
between cases and controls. However, among women with alpha diversity below the median
(low), there was a strong association between increasing numbers of yeast infections
and vulvodynia onset, relative to comparable time periods among controls (age-adjusted
odds ratio, 8.1, 95% confidence interval, 2.9–22.7 in those with 5 or more yeast infections).
Also among women with low-diversity microbiomes, we observed a strong association
between moderate to severe childhood abuse, antecedent anxiety, depression, and high
levels of rumination and vulvodynia with odds ratios from 1.83 to 2.81. These associations
were not observed in women with high-diversity microbiomes.
Conclusion
Although there were no overall differences in microbiome profiles between cases and
controls, vaginal microbiome diversity influenced associations between environmental
and psychosocial risk factors and vulvodynia. However, it is unclear whether vaginal
diversity modifies the association between the risk factors and vulvodynia or is altered
as a consequence of the associations.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & GynecologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Prevalence of symptoms consistent with a diagnosis of vulvodynia: population-based estimates from 2 geographic regions.Am J Obstet Gynecol. 2014; : 21040.e1-21040.e8
- Assessment of vulvodynia symptoms in a sample of US women: a prevalence survey with a nested case control study.Am J Obstet Gynecol. 2007; 196: 128.e1-128.e6
- Vulvodynia: definition, prevalence, impact and pathophysiological factors.Sexual Medicine. 2016; 13: 291-304
- Vulvodynia: what we know and where we should be going.J Lower Gen Tract Dis. 2017; 21: 1-7
- Elevated tissue levels of interleukin-1 beta and tumor necrosis factor-alpha in vulvar vestibulitis.Obstet Gynecol. 1997; 89: 291-296
- Interleukin-1β gene polymorphism in women with vulvar vestibulitis syndrome.Eur J Obstet Gynecol Reprod Biol. 2003; 107: 74-77
- Allergic reactions and risk of vulvodynia.Ann Epidemiol. 2009; 19: 771-777
- Recurrent yeast infections and vulvodynia: can we believe associations based on self-reported data?.J Womens Health. 2017; 26: 1069-1076
- In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis.Sci Rep. 2018; 8: 2307
- Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women.Immunity. 2017; 46: 29-37
- The bacterial microbiome in paired vaginal and vestibular samples from women with vulvar vestibulitis syndrome.Pathogens Dis. 2014; 72: 161-166
- Vulvovestibular syndrome and vaginal microbiome: a simple evaluation.J Clin Med Res. 2018; 10: 688-692
- ISSVD, ISSWSH, and IPPS consensus terminology and classification of persistent vulvar pain and vulvodynia.J Lower Gen Tract Dis. 2016; 20: 1-5
- Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform.Appl Environ Microbiol. 2013; 79: 5112-5120
- Minimum entropy decomposition: unsupervised oligotyping for sensitive partitioning of high-throughput marker gene sequences.ISME J. 2015; 9: 968-979
- Oligotyping: differentiating between closely related microbial taxa using 16S rRNA gene data.Methods Ecol Evol. 2013; 4: 1111-1119
- DADA2: high-resolution sample inference from Illumina amplicon data.Nat Methods. 2016; 13: 581-583
- Dirichlet multinomial mixtures: generative models for microbial metagenomics.PloS One. 2012; 7e30126
- R: a language and environment for statistical computing.R Foundation for Statistical Computing, Vienna, Austria2017 (Available at:)
- DirichletMultinomial: Dirichlet-Multinomial Mixture Model Machine Learning for Microbiome Data. Buffalo, NY: R package version 1.28.0;.2019
- Analysis of matched case control studies.Br Med J. 2016; 352: i969
- ANOVA-like differential gene expression analysis of single-organism and Meta-RNA-Seq.PLoS One. 2013; 8: e67019
- Ecological dynamics of the vaginal microbiome in relation to health and disease.Am J Obstet Gynecol. 2019; : 324-335
- Molecular identification of bacteria associated with bacterial vaginosis.N Engl J Med. 2005; 353: 1899-1911
- Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort.PLoS One. 2013; 8e63514
- Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women.ISME J. 2014; 8: 1781-1793
- Vaginal microbiome and its relationship to behavior, sexual health, and sexually transmitted diseases.Obstet Gynecol. 2017; 129: 643-654
- Diversity is the question, not the answer.ISME J. 2017; 11: 1-6
- The vaginal microbiome during pregnancy and the postpartum period in a European population.Sci Rep. 2015; 5: 8988
- Recurrent vulvovaginal candidiasis.Am J Obstet Gynecol. 2016; 214: 15-21
- Vulvovaginal candidiasis: epidemiology, microbiology and risk factors.Crit Rev Microbiol. 2016; 42: 905-927
- Population cycles and species diversity in dynamic Kill-the-Winner model of microbial ecosystems.Sci Rep. 2017; 7: 39642
- Vaginal microbiome of reproductive-age women.Proc Natl Acad Sci USA. 2011; 108: 4680-4687
Article info
Publication history
Published online: March 02, 2020
Accepted:
February 21,
2020
Received in revised form:
February 15,
2020
Received:
August 15,
2019
Footnotes
This study was supported by the National Vulvodynia Association and National Institutes of Health–Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01 HD058608.
The authors report no conflict of interest.
Cite this article as: Bedford L, Parker SE, Davis E, et al. Characteristics of the vaginal microbiome in women with and without clinically confirmed vulvodynia. Am J Obstet Gynecol 2020;223:406.e1-16.
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
