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Meta-Analysis
. 2023 Sep 13:14:1241962.
doi: 10.3389/fendo.2023.1241962. eCollection 2023.

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review

Wenxin Ma  1 , Xiaowen Zhang  1 , Ruotong Zhao  2 , Yang Tang  2 , Xiaoyun Zhu  3 , Longkun Liu  2 , Mingyuan Xu  2 , Ge Wang  4 , Peiyue Peng  2 , Jianping Liu  1   5 , Zhaolan Liu  1
Affiliations
Meta-Analysis

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review

Wenxin Ma et al. Front Endocrinol (Lausanne). .

Abstract

Objectives: To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs (ATDs) in the treatment of hyperthyroidism.

Methods: Eight databases and three trial registries were searched from inception until May 2023. Randomized controlled trials (RCTs) were included and meta-analysis was conducted using RevMan 5.4 and Stata 14.0. The Cochrane risk of bias (ROB) tool 1.0 and GRADE tool was used for quality appraisal. The findings from case reports using mono-JWXYS and pharmacological studies were summarized in tables.

Results: Thirteen RCTs with 979 participants were included. The majority of the included studies were assessed as high risk of bias in one ROB domain. Compared with ATDs, JWXYS plus ATDs resulted in lower free triiodothyronine (FT3) (MD = -1.31 pmol/L, 95% CI [-1.85, -0.76]; low-certainty), lower free thyroxine (MD = -3.24 pmol/L, 95% CI [-5.06, -1.42]; low-certainty), higher thyroid stimulating hormone (MD = 0.42 mIU/L, 95% CI [0.26, 0.59]; low-certainty), higher effectiveness rate of traditional Chinese medicine syndrome (RR = 1.28, 95% CI [1.08, 1.52]; low-certainty), lower goiter score (MD = -0.66, 95% CI [-1.04, -0.29]; very low-certainty), lower thyrotrophin receptor antibody (SMD = -0.44, 95% CI [-0.73, -0.16]; low-certainty) and fewer adverse events (AEs) (RR = 0.34, 95% CI [0.18, 0.67]; moderate-certainty). Compared with regular dosage of ATDs, JWXYS plus half-dose ATDs resulted in fewer AEs (RR = 0.24, 95% CI [0.10, 0.59]; low-certainty). Compared with ATDs in 1 trial, JWXYS resulted in higher FT3, lower goiter score and fewer AEs. Three case reports showed that the reasons patients sought TCM-only treatment include severe AEs and multiple relapses. Three pharmacological studies demonstrated that JWXYS restored Th17/Treg balance, lowered deiodinases activity, regulated thyroid cell proliferation and apoptosis, and alleviated liver oxidative stress in mouse or rat models.

Conclusion: JWXYS may enhance the effectiveness of ATDs for hyperthyroidism, particularly in relieving symptoms and reducing AEs. Mono-JWXYS is not recommended except in patients intolerant to ATDs. The findings should be interpreted with caution due to overall high risk of bias. Further pharmacological studies with more reliable models are needed.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023394923.

Keywords: Jiawei-Xiaoyao-San; hyperthyroidism; meta-analysis; pharmacological studies; randomized controlled trials; systematic review; traditional Chinese medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of study selection process. CNKI, China National Knowledge Infrastructure; VIP, Chongqing Chinese Science and Technology Journal Database; SinoMed, China BioMedical Literature Service System; ICTRP, the WHO International Clinical Trials Registry Platform; n, number; RCT, randomized controlled trails. Template for the flow diagram was provided by PRISMA.
Figure 2
Figure 2
Risk of bias summary of 13 included RCTs.
Figure 3
Figure 3
Forest plots of the effectiveness comparison on thyroid functions. (A): Free triiodothyronine, (B): Free thyroxine, (C): Thyroid stimulating hormone. JWXYS, Jiawei-Xiaoyao-San; ATD, antithyroid drug; L-ATD, half-dose antithyroid drug.
Figure 4
Figure 4
Forest plots of the effectiveness comparison on traditional Chinese medicine (TCM) syndrome. (A): Effectiveness rate of TCM syndrome, (B): TCM syndrome score. JWXYS, Jiawei-Xiaoyao-San; ATD, antithyroid drug; L-ATD, half-dose antithyroid drug.
Figure 5
Figure 5
Forest plots of the effectiveness comparison on goiter score. JWXYS, Jiawei-Xiaoyao-San; ATD, antithyroid drug; L-ATD, half-dose antithyroid drug.
Figure 6
Figure 6
Forest plot of the effectiveness comparison on TRAb. JWXYS, Jiawei-Xiaoyao-San; ATD, antithyroid drug.
Figure 7
Figure 7
Forest plots of adverse events in different comparisons. JWXYS, Jiawei-Xiaoyao-San; ATD, antithyroid drug; L-ATD, half-dose antithyroid drug.
Figure 8
Figure 8
Sensitivity tests of primary outcomes in the comparison between Jiawei-Xiaoyao-San plus antithyroid drugs (ATDs) and mono-ATDs. (A): Free triiodothyronine, (B): Free thyroxine, (C): Thyroid stimulating hormone.
Figure 9
Figure 9
Subgroup analyses classified by course of intervention of primary outcomes in the comparison between Jiawei-Xiaoyao-San plus antithyroid drugs (ATDs) and mono-ATDs. (A): Free triiodothyronine, (B): Free thyroxine, (C): Thyroid stimulating hormone.
Figure 10
Figure 10
Funnel plots and Egger’s tests of the effectiveness on free triiodothyronine (A) and free thyroxine (B) reported by 10 included trials in the comparison between Jiawei-Xiaoyao-San plus antithyroid drugs (ATDs) and mono-ATDs.
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