Elucidating the relationships between vulvodynia, immune conditions, and the vaginal microbiome
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Abstract
INTRODUCTION: Vulvodynia is a poorly understood chronic gynecological pain condition that affects 7-8% of women by age 40. To shed light into its complex etiology, we aimed to elucidate the relationship between chronic immune conditions (a known contributor to vulvodynia) and the vaginal microbiome using data from a clinically-confirmed case-control study of vulvodynia.
METHODS: We analyzed data from a case-control study of 213 vulvodynia cases and 220 controls who were recruited from a large healthcare system in the St. Paul/Minneapolis region. We used a directed acyclic graph (DAG) to depict hypothesized relationships between variables. We created a binary variable indicating a history of any chronic immune condition. Vaginal microbiome diversity was assessed using the Shannon alpha diversity index (dichotomized above/below the sample median), and community state type (CST) was identified using an unsupervised clustering method. We calculated adjusted odds ratios (aORs) relating microbiome characteristics to vulvodynia using logistic regression models which we stratified by a history of immune conditions. We also calculated adjusted odds ratios (aORs) relating a history of immune conditions to vulvodynia using logistic regression models which we stratified by microbiome characteristics (alpha diversity and CST).
RESULTS: We saw no evidence of effect modification of the association between alpha diversity and vulvodynia by a history of chronic immune conditions. When evaluating CST, stratification by a history of immune conditions resulted in two aORs in different directions. The aOR for CST 1-3 vs CST 4-6 was 1.54 (95% CI: 0.91-2.62) among those with an immune condition, whereas the odds of vulvodynia was 0.49 (95% CI: 0.22-1.06) for those without immune conditions, raising the possibility of effect modification. We also stratified analyses by microbiome characteristics but interpreted these findings with caution due to the possibility of collider stratification bias, which is demonstrated by our post-study DAG.
CONCLUSION: Our findings suggest that the relationship between vulvodynia in reproductive-aged women and a history of immune conditions may be modified by some characteristics of the vaginal microbiome (CST) but not others (alpha diversity). Methodologically, our study also highlights the utility of DAGs in elucidating complex relationships in disease processes involving multiple variables.
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2025