Oral versus topical maintenance antifungal therapy for recurrent vulvovaginal candidiasis: A systematic review and meta-analysis

Abstract Background Recurrent vulvovaginal candidiasis is a substantial personal and healthcare burden. This systematic review assessed the effects of topical versus oral maintenance antifungal therapy in women with recurrent vulvovaginal candidiasis to improve outcomes. Methods We conducted a comprehensive search of bibliographic databases (CENTRAL, MEDLINE/PubMed), citation indexes (Web of Science, Scopus), and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) from inception to March 2025, without language or publication status restrictions. We screened reference lists of relevant studies and systematic reviews. We included randomized trials comparing topical versus oral maintenance antifungal therapy for recurrent vulvovaginal candidiasis. Three reviewers independently screened the records, assessed the full texts, extracted the data, and assessed the risk of bias. The primary outcome was the proportion of participants with no clinical or mycological recurrence at the end of follow-up. We performed a common-effect meta-analysis. We used the GRADE approach to assess the certainty of evidence and generate a summary of findings table. Results We included six trials (1224 participants). All studies included women with recurrent vulvovaginal candidiasis. In the oral arm, five studies used fluconazole and one study used itraconazole. In the topical arm, three studies used clotrimazole, one used a combination of clotrimazole-diclofenac, one used fenticonazole, and one used nystatin. Five studies continued outcome measurement for six months after completion of the maintenance phase. Most of the included studies were judged to be at high risk of bias. The pooled estimates of the effects are not significantly different across all outcomes, including clinical or mycological recurrence, satisfaction, and adverse events. The evidence for all outcomes was very uncertain due to serious methodological concerns and imprecision. Conclusions The evidence is very uncertain about the benefits and harms of oral versus topical antifungal maintenance therapy for women with recurrent vulvovaginal candidiasis. Given the substantial personal and healthcare burden of the condition, the uncertainty of the evidence leaves a crucial gap in guidance for clinicians and patients when choosing a maintenance strategy. Review Registration: OSF osf.io/g7fzy