Anti-Dysmenorrhea Effects and Safety of Guizhi Fuling Capsules for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Primary dysmenorrhoea is common and disabling, while available treatments may be limited by incomplete response or adverse effects. We aimed to evaluate the efficacy and safety of Guizhi Fuling Capsules (GZFL) for primary dysmenorrhoea. METHODS: We searched eight English- and Chinese-language databases from inception to 1 December 2025 for randomized controlled trials comparing GZFL, alone or as add-on therapy, with placebo or conventional medicines. Meta-analyses used risk ratios (RRs), odds ratios (ORs), or mean differences (MDs) with 95% confidence intervals (CIs). Risk of bias and certainty of evidence were assessed using the Cochrane tool and GRADE. RESULTS: The searches identified 294 records, of which 14 trials involving 1280 participants met the eligibility criteria. All trials were conducted in China and were short-term, generally covering three menstrual cycles. GZFL-based regimens were associated with higher trial-defined pain-relief rates (11 trials, 1014 participants; RR 1.62, 95% CI 1.23-2.14; I2 = 62%) and total effective rates (11 trials, 1014 participants; RR 1.42, 95% CI 1.17-1.73; I2 = 89%). VAS evidence from three trials (295 participants) was inconclusive (MD -1.26, 95% CI -4.21 to 1.70; I2 = 98%). Four trials (512 participants) contributed safety data; adverse events were generally mild (OR 0.42, 95% CI 0.23-0.76; I2 = 17%). Biomarkers were reported in few trials: IL-6 was inconclusive, while lower IL-10 and TNF-alpha estimates remained mechanistically uncertain. CONCLUSION: Short-term randomized evidence suggests that GZFL-based regimens may improve categorical pain response and total effective rate and may be well tolerated, whereas the pooled VAS result was inconclusive. Confidence is limited by heterogeneity, incomplete reporting, short follow-up, and exclusively Chinese settings; longer, rigorously designed trials with standardized outcomes are needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD420251271957.