Effects of Flourish HEC Vaginal Care System on Reduction of Pain in Women With Localized Provoked Vulvodynia

Vulvodynia is a chronic pain condition affecting the tissues of the external genitalia in women. Localized provoked vulvodynia (LPV) is a specific subset of vulvodynia in which pain occurs upon touching specific sites on the vestibule (or, less commonly, another defined area), and which has been present for more than three months without a known cause. LPV is characterized both by allodynia (pain in response to a normally non-painful stimulus) and hyperalgesia (excessive pain response), leading to pain with sex, tampon use, and even with activities of daily life, such as sitting or wearing tight clothing.

It is becoming accepted that LPV occurs as a type of hypersensitivity to Candida and other antigens which occurs in susceptible women. LPV is an inflammatory condition with increased levels of B-cells, T-cells, and macrophages in tender areas vs. non-tender areas. The inflammatory process sparks neuroproliferation - growth of new nerve endings - which increases the density of nerve fibers in tender spots, especially in areas of lymphoid aggregates.

The vulvar and vaginal microbiomes are connected to each other; species found in one are often found in the other. In fact, Jayaram et al. showed that all vaginal species were also found on the vestibule, and the dominant vaginal species is also the dominant vestibular species, suggesting that vaginal secretions are a major contributor to the vestibular/vulvar microbiome. Three recent studies have examined the link between vulvodynia and the vaginal microbiome. Results vary by study, with one showing differences in the present vaginal microbiomes between women with vulvodynia and healthy women, and others not showing differences. These may be explainable by inclusion/exclusion criteria (two studies excluded women with active yeast infection; one study specified studying generalized, not localized, vulvodynia; while the others did not specify). But it is agreed that past alterations in the microbiome primed women for excessive pain in response to gentle stimuli.

Vaginal microbiome composition is known to affect immune activation in the vagina and vulva. Campisciano and colleagues showed that vaginal dysbiosis is associated with elevated levels of interleukin (IL)-1ra and IL-2, and lower levels of fibroblast growth factor (FGF)-beta and granulocyte-macrophage colony stimulating factor (GM-CSF) than observed in healthy vaginas. Another study by the same group reported associations between vaginal microbiome composition and IL-1alpha and IL-18. Doerflinger showed activation of the innate immune response by Lactobacillus iners (intermediate flora) and Fannyhessea vaginae (associated with bacterial vaginosis), but not L. crispatus (healthy flora). Of greatest relevance, Falsetta and colleagues investigated expression and activation of the toll-like receptor family and found seven of them to be expressed at higher levels in tissue biospies from tender spots in LPV than in control tissue, and that exposure to HIV increased expression of TLR7 expression and the downstream inflammatory molecule IL-6. Notably, no studies have examined whether improving the vaginal microbiome might lead to reductions in immune signaling in vulvodynia.

Taken together, it is reasonable to hypothesize that the constitution of the vaginal microbiome may influence the hypersensitivity to allergens that comprises the cause of LPV. It is also possible that improving the vaginal microbiome may reduce immune cell recruitment and activation, reducing pain. It is predicted that using sequencing-based technology, differences between the vaginal microbiomes of women with LPV and those without will be detectable. Furthermore, its is predicted that using an over-the-counter feminine hygiene system designed to support a healthy vulvovaginal microbiome will reduce pain in women with LPV over and above any reductions observed with standard-of-care treatment.