Beyond the placebo effect: a systematic review and a network meta-analysis of treatment strategies for vulvodynia

To comprehensively evaluate the comparative and absolute effectiveness of available treatments for vulvodynia on pain and sexual function outcomes through network meta-analysis (NMA). Systematic searches extracted data from randomized controlled trials (blinded or unblinded) evaluating pharmacological and non-pharmacological treatments in women with vulvodynia, from inception through September 2025. Of 40 studies assessed for eligibility, 34 studies involving 1,893 participants were included in the final analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2 tool.Confidence in network meta-analysis results was evaluated using the Confidence in Network Meta-analysis (CINeMA) framework. Pain and sexual function outcomes were rescaled to percentage of maximum possible score (POMP, 0–100 scale) to enable pooling across heterogeneous measurement instruments. Both relative treatment effects (comparing interventions to placebo/no treatment) and absolute effects (pre-post changes) were evaluated using Bayesian NMA. Ten treatment categories were analysed: acupuncture, botulinum toxin, topical anaesthetics, topical non-anaesthetics, multimodal/physical therapy, psychological approaches, surgery, tissue-based therapies (photobiomodulation, low-level laser, vaginal transcutaneous electrical nerve stimulation, shockwave therapy), placebo, and no treatment. For pain immediately post-therapy (33 studies, 1,873 women), tissue-based therapies demonstrated superior efficacy compared to placebo in both NMA (POMP difference: -16.1, 95% CI: -24.1, -7.9, mixed evidence, moderate confidence), and pairwise meta-analyses (POMP difference: -20.2, 95% CI: -28.6, -11.7, I2 = 77%) and ranking highest in surface under the cumulative ranking curve (SUCRA) analysis (85.2%). Pharmacological interventions showed no superiority over placebo. Compared to no treatment, multimodal-physical therapy (POMP: -25.3, 95% CI: -40.8, -9.7, mixed evidence, low confidence), acupuncture (POMP: -25.6, 95% CI: -43.4, -8.1, mixed evidence, moderate confidence), and psychological approaches (POMP -27.4, 95% CI: -44.6, -10.3, indirect evidence, low confidence) all demonstrated moderate-to-high pain reduction. At 3–6 months follow-up (16 studies, 1,106 women), tissue-based treatments remained the only therapy significantly superior to placebo (POMP: -24.5, 95% CI: -42.2, -6.7, mixed evidence, moderate confidence; SUCRA = 77.9%). In absolute effects analysis, placebo produced significant pain reduction (Absolute effect: -13.7, 95% CI: -18.3, -9.3 immediately; -11.7, 95% CI: -17.7, -6.0 at 3–6 months), with confidence intervals overlapping all treatments except tissue-based therapies (Absolute effect: -28, 95% CI: -33.4, -21.7 immediately; -31.6, 95% CI: -43.9, -19.1 at follow-up). Placebo had no effect on sexual function improvement (14 studies, 942 women), (Absolute effect: 2.5, 95% CI: -8., 12.9). At 3–6 months of follow-up (8 studies, 429 women), psychological-based treatments, when added to multimodal treatment (POMP = 9.0, 95% CI = 1.8, 16.7, I2 = 41.6%), improved modestly sexual functioning. In NMA, tissue-based therapies were the most effective treatment for vulvodynia-associated pain, achieving reductions that clearly exceeded placebo effects with moderate evidence quality. Commonly prescribed pharmacological interventions lack robust evidence of superiority over placebo. Multimodal approaches combined with psychological interventions show promise, particularly for sexual function recovery.