Characteristics of the vaginal microbiome in women with and without clinically confirmed vulvodynia.

Bedford, Lisa; Parker, Samantha E; Davis, Elyse; Salzman, Elizabeth; Hillier, Sharon L; Foxman, Betsy; Harlow, Bernard L

BACKGROUND Vulvodynia (idiopathic vulvar pain) affects up to 8% of women by age 40, has a poorly understood etiology, and variable treatment efficacy. Several risk factors are associated with vulvodynia from history of yeast infections to depression and allergies. Recent work suggests an altered immune inflammatory mechanism plays a role in vulvodynia pathophysiology. As the vaginal microbiome plays an important role in local immune-inflammatory responses, we evaluated the vaginal microbiome among women with vulvodynia compared to controls as one component of the immune system. OBJECTIVE 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 [OR] 8.1, 95% CI: 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 ORs from 1.83 to 2.81. These associations were not observed in women with high diversity microbiomes. CONCLUSIONS 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.