With the Identification of a High-Risk Group for the Development of Vulvodynia Comes an Eye on Prevention

It has been 6 years since an interdisciplinary consensus panel published their recommendations on the future direction of vulvodynia research. ¹ The consensus panel stated that the establishment of the natural progression of vulvodynia was critical to further addressing clinical and research priorities; however, it was also noted that there was a dearth of data on the topic. An article in this issue of the Journal brings the field one important step closer to improved description of the natural progression, specifically from a nondisease state to vulvodynia. ²

Using a population-based sample, Reed et al. ² identified a group of women who exhibit an increased risk of vulvodynia, defined by validated self-reported symptoms using a survey method. The authors found that the risk of incident vulvodynia in the follow-up of up to 4 years was 5.6/100 women-years for women who had what the authors termed an intermediate phenotype of vulvodynia. The intermediate phenotype was defined as pain with intercourse within the last 6 months but no vulvar pain or as vulvar pain but not meeting the criteria for chronic pain (generally defined as lasting 3 months). This incidence was in stark contrast to the incidence for women who had never experienced pain with intercourse and who had never had vulvar pain. The incidence in these strict control women was 1.4/100 women-years, which was consistent with a previous report by the same group. ³ The incidence rate for the strict controls was significantly lower than what was observed for the group with an intermediate phenotype. Somewhat masking this heterogeneity was the overall incidence rate of 3.1/100 women-years. This overall rate is similar to one reported in a different population by Sutton et al. ⁴ at 4.7/100 women-years. When focusing on just the 288 women who report intermediate phenotypes and who exhibited a high risk of vulvodynia, there were certain factors that further increased their risk, including being nonwhite, pain after intercourse, and urinary burning.

In Reed et al., ² the incidence of vulvodynia was reduced by 54% for white women compared to nonwhite women. This finding is consistent with a previous population-based study by Harlow and Stewart, ⁵ which found that Latina women in the Boston area were 80% more likely to be classified as having vulvodynia than white women. Reed et al., as with other population-based studies on vulvodynia, ^6,7 chose to adjust their multivariable models for effects of race. (Some other studies may not have had enough racial diversity for the need to adjust for race.) To date, however, there have been no published studies adequately powered to determine if there are truly racial differences in the incidence or prevalence of vulvodynia.

The additional finding that intermediate symptoms, such as pain after intercourse and urinary burning, increase a woman's risk for vulvodynia simply makes sense. For example, dyspareunia is a hallmark feature of localized, provoked vulvodynia. ⁸ Among this high-risk group, a history of pain with intercourse exhibited a risk similar to that with pain after intercourse (adjusted incidence rate ratio [IRR] 3.41 vs. 3.05, respectively), although the finding for a history of pain with intercourse did not reach statistical significance. Those who report pain after sex were fewer. Therefore, it is feasible that those who had pain after sex also experienced pain during sex, perhaps indicating a more severe pathology and reflecting a better precision in the estimate (and a significant p value), whereas women who experience urinary burning may have a history, perhaps a recent or recurrent history, of urogenital infections. These types of infections have been associated with vulvodynia in multiple epidemiologic studies. ^7,9,10 In addition, a dose-response with the number of infections has been observed. ⁷ Findings at the population level have been supported by laboratory studies; recent evidence from a murine model of vulvodynia introduced repeated Candida albicans infection, causing hyperinnervation with peptidergic nociceptor and sympathetic fibers in genital tract epithelium. ¹¹

One of the most important implications of identifying a high-risk group is the opportunity to develop interventions to prevent disease from occurring (primary prevention), in this case, vulvodynia. If that is not possible, secondary prevention programs, which aim to efficiently identify cases early in their development to avoid biologic and psychosocial sequelae, should be implemented. It is important to note, however, that it remains unclear at this point if these high-risk women have already initiated their conversion to vulvodynia, with the remaining women developing it later (the study had only a 4-year follow-up). In this scenario, primary prevention may not be possible, but it is probably safe to hypothesize that not all of these 288 high-risk women ultimately develop vulvodynia. Therefore, the next challenge is some type of prevention. Thus, interventions aimed at these high-risk women are warranted.

Prevention of vulvodynia is unfortunately far from our sights. However, continued contribution to the identification of at-risk groups and disease progression, such as the Reed et al. study, ² moves the field one step closer. Future research examining the risk of vulvodynia in women of color, particularly Latinas, should be encouraged. In addition, studies further describing the progression of disease should focus on natural fluctuations in vulvar pain that may or may not reach current clinical definitions. Factors that may influence fluctuation in symptoms, such as urogenital infections, should be investigated. Should there be an association between urogenital infection and fluctuations in vulvar pain, treatment for the preceding conditions could be a means to prevention of vulvodynia. With these studies, particularly if they are observational and not clinical trials, care should be taken in the data analysis to account for possible confounding by disease severity. Providing treatment according to the severity of the infection could potentially cause misinterpretion of the study findings regarding treatment on the development of vulvodynia. ¹²

In summary, as with much about vulvodynia, the annual incidence is seemingly heterogeneous. A high-risk group of women for the development of diagnosable vulvodynia is women showing some component of vulvodynia, such as pain with first tampon insertion or intercourse and vulvar burning. Even within this high-risk group, however, additional factors may increase the risk of vulvodynia diagnosis, and these factors include nonwhite race, pain after intercourse, and burning with urination. Priorities for vulvodynia research can now evolve into theories for primary or secondary prevention of this consuming condition.