Ask the Expert: Vulvodynia and the Biome

Ask the Expert: Vulvodynia and the Biome

May 2022

We are pleased to continue our series here on Evolving Women's Health blog called Ask the Expert with Chief Science Officer Elizabeth DuPriest, Ph.D. Have a question about vaginal biome science? Submit yours here and your answer may be featured in an upcoming newsletter.

Q: How does the biome relate to vulvodynia?

A: Vulvodynia is defined as pain of the vulva lasting at least 3 months with no identifiable cause. Vulvodynia may be classified as localized, generalized, or mixed, with localized vulvodynia often restricted to either the vestibule or the clitoris. Further, it may be classified as either provoked, spontaneous, or mixed. Onset may be primary or secondary. The temporal pattern may be intermittent, persistent, constant, immediate, or delayed. Painful sensations are often described as burning but may also be described as sharp, tearing, stinging, rawness, or even itching. Intensity of pain may be mild, moderate, or severe, and involves both allodynia (pain in response to stimuli that are not typically painful) and hyperalgesia (excessive pain sensation). In short, the pain of vulvodynia may be experienced in a number of ways, and it can have profound impacts on quality of life. As many as 16% of women may experience vulvodynia at some point in their lives.

Research so far has shown few weak associations between vulvodynia and the vulvar or vaginal microbiome at the time of diagnosis. However, several studies have shown that women with vulvodynia have a history of multiple yeast infections. It is becoming scientific consensus that some women, who have yet-to-be-determined susceptibility factor(s), develop a hypersensitivity to Candida or possibly other vulvovaginal infection. This stimulates an inflammatory immune response that generates aggregates of immune cells – T cells, B cells, and macrophages – in tender spots, along with sprouting of new nerve fibers near these aggregates. It is this neuroproliferation that is thought to contribute directly to the hyperalgesia and allodynia.

Toll-like receptors (TLRs) are key proteins expressed mostly in macrophages and dendritic cells which detect foreign antigens and activate the immune response to them. Interleukin-6 and other cytokines and chemokines are downstream mediators of TLR action. In localized provoked vulvodynia, seven of the nine TLRs show increased expression, revealing possible pathways for hypersensitivity and hyperreactivity of the immune response. Only a few studies have examined the vaginal microbiome in vulvodynia, and they have generally shown small, inconsistent effects. However, studies have shown that various bacterial species commonly found in the vagina – Lactobacillus crispatus, L. iners, and Gardnerella vaginalis – affect vaginal fluid immune marker levels in differing ways, suggesting that presence or abundance of specific individual or combinations of bacteria might alter the immune response in ways that contribute to or suppress the development and persistence of vulvodynia.

Overall, it seems that there is a complex interaction between microbes and the host immune response that underlies the condition but is yet to be fully understood. More study is desperately needed to understand the causes and pathophysiology of vulvodynia so that better remedies can be found.


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Park SY, Lee ES, Lee SR, Kim SH, Chae HD. Vaginal Microbiome Is Associated With Vulvodynia, Vulvar Pain Syndrome: A Case-Control Study. Sex Med. 2021;9(2):100314. doi:10.1016/j.esxm.2020.100314

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(3):406.e1-406.e16. doi:10.1016/j.ajog.2020.02.03

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Falsetta ML, Foster DC, Woeller CF, et al. Toll-Like Receptor Signaling Contributes to Proinflammatory Mediator Production in Localized Provoked Vulvodynia. J Low Genit Tract Dis. 2018;22(1):52-57. doi:10.1097/LGT.0000000000000364

Murina F, Caimi C, Di Pierro F, Di Francesco S, Cetin I. Features of the Vaginal and Vestibular Microbioma in Patients With Vestibulodynia: A Case-Control Study. J Low Genit Tract Dis. 2020;24(3):290-294. doi:10.1097/LGT.0000000000000523

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