A meta-umbrella review of risk factors for vulvodynia: evidence from demographic, psychosocial, and biomedical domains

Vulvodynia is a chronic vulvar pain condition significantly affecting the quality of life. Its multifactorial etiology is not fully understood, and comprehensive pooled data on associated risk factors are lacking due to heterogeneous research. This umbrella review addresses this gap.

This systematic umbrella review and meta-analysis aims to synthesize existing evidence on demographic, psychosocial, and biomedical risk factors associated with vulvodynia. We seek to quantitatively evaluate the strength of these associations, assess the quality of information in the current literature, and determine the clinical impact of each identified risk factor.

Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), we searched major databases for meta-analyses, systematic reviews, and comparative observational studies. We included potential risk factors with ≥100 vulvodynia cases. Risk of bias was assessed via Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E); data were analyzed using the metaumbrella in R, measuring associations as equivalent odds ratios (eORs) with 95% confidence intervals. Evidence was stratified into 5 classes using 2 different approaches evaluating the strength and quality of the evidence.

We identified 15 meta-analyses, 28 systematic reviews, and 129 primary studies (87 from reviews/meta-analyses and 42 from individual searches) (30 095 vulvodynia cases and 14 928 868 controls from 1993 to 2025). Convincing or very suggestive evidence of association included: fibromyalgia (eOR = 2.62, 95% CI, 2.06-3.35), recurrent urinary tract infection (eOR = 3.12, 95% CI, 2.16-4.48), recurrent vulvovaginal candidiasis (eOR = 3.07, 95% CI, 2.38-3.96), irritable bowel syndrome (eOR = 2.79, 95% CI, 2.24-3.49), anxiety (eOR = 2.7, 95% CI, 2.18-3.4), depression (eOR = 2.56, 95% CI, 1.92-3.4), systemic inflammation (eOR = 2.30, 95% CI, 1.76-3.00), and allergy/atopy (eOR = 1.83, 95% CI, 1.52-2.22). Suggestive evidence was found for interstitial cystitis (eOR = 9.11, 95% CI, 3.27-25.42), endometriosis (eOR = 5.39, 95% CI, 2.25-12.93), and younger age (eOR = 0.51, 95% CI, 0.37-0.69). Additional 23 psychosocial and biomedical factors also showed significant associations with varying degrees of evidence. Subgroup analysis for generalized/unspecific vulvodynia showed similar results with reduced heterogeneity.

This meta-umbrella review identifies numerous factors strongly associated with vulvodynia, highlighting its multifactorial nature. These findings are crucial for clinical history and future research.