Efficacy of Xiaoyao-San preparations in treating Hashimoto's thyroiditis: A meta-analysis and systematic review

Chengna Wang^1,2,3Wenxin Ma⁴Lingling Qin^1,5Lili Wu^1,3Tonghua Liu^1*

• ¹Beijing University of Chinese Medicine, Beijing, China
• ²The Second Clinical Medical School, Beijing University of Chinese Medicine, Beijing, China
• ³Key Laboratory of Health Cultivation of Traditional Chinese Medicine, the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China
• ⁴Centre for Evidence-Based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
• ⁵Science and Technology Division, Beijing University of Chinese Medicine, Beijing, China

Objective: To assess Xiaoyao-San (XYS) preparations' effectiveness in treating Hashimoto's thyroiditis.Methods: Eight databases were searched for randomized controlled trials (RCTs) comparing XYS preparations to a low-iodine diet (LID), selenium yeast (SY), levothyroxine (LT4), or Ophiocordyceps sinensis (OS) for HT treatment. The datasets from inception to September 2024. Two reviewers independently evaluated literature and research biases. Meta-analysis was done with Revman 5.4. The GRADE technique assessed evidence reliability. Robustness was assessed using sensitivity and trial sequential analysis (TSA).Results: This study analyzed seven randomized controlled trials involving 612 patients. Metaanalysis demonstrated that XYS preparations significantly reduced TPOAb levels [SMD = -0.74, 95% CI (-1.02, -0.46), p < 0.00001]. Combining LT4 with XYS preparations resulted in greater TPOAb reduction compared to LT4 alone [SMD = -0.77, 95% CI (-1.06, -0.47), p < 0.00001] and was more effective in lowering TgAb levels [SMD = -0.66, 95% CI (-1.05, -0.26), p = 0.001]. XYSJW outperformed OS in reducing TgAb [SMD = -0.35, 95% CI (-0.58, -0.10), p = 0.005]. Four XYS preparations (XY, HHXY, GQXY, and DZXY) increased FT3 and FT4 levels [SMD = 0.13, 95% CI (0.01, 0.61), p = 0.04; SMD = 0.58, 95% CI (0.12, 1.04), p = 0.01] and decreased TSH [SMD = -0.76, 95% CI (-0.98, -0.54), p < 0.00001]. Subgroup analysis indicated XY significantly improved FT3 and FT4 levels, but XYS preparations combined with LT4 did not enhance FT3/FT4 restoration. XYSJW also did not reduce TSH more effectively than OS. Evidence quality was low or very low. TSA confirmed the pooled effect estimates, with cumulative z-curves for TPOAb, TgAb, and TSH surpassing the benefit threshold.Combination therapy with XYS preparations and LT4 may reduce TPOAb, TgAb, and TSH levels in HT patients. XY combined with LID or SY therapy is more effective at restoring FT3 and FT4 levels. While XYSJW outperforms OS preparations in lowering TgAb levels, it may not surpass OS in restoring thyroid hormone levels. Most studies reviewed are of low quality. XYS preparations appear to modulate cytokines by targeting immune markers and reducing inflammation, but their safety profile remains unclear, requiring further robust evidence.