1 Introduction
Uterine leiomyoma (UL), also known as fibroma or leiomyoma, is a female gynecologic tumor[1] [2] [3,4] [5] [6] [7]
Traditional Chinese medicine (TCM) has been used in the treatment of diseases for thousands of years and has gained the overwhelming trust of patients through its history of positive therapeutic effects. Xuefu Zhuyu Decoction (XFZYD) is composed of the peach kernel (Tao Ren), safflower (Hong Hua), angelica (Dang Gui), radix rehmanniae (Sheng Di), chuanxiong rhizome, red peony root (Chi Shao), achyranthes root (Niu Xi), balloonflower (Jie Geng), Chinese thorowax (Chai Hu), bitter orange (Zhi Ke), and glycyrrhiza (Gan Cao).[8] Xuefu Zhuyu Decoction has a good effect on diseases of nervous system, digestive system, cardiovascular system, and obstetrics and gynecology.[9] [10] [11] [12] [13]
Some clinical studies published in China have shown that XFZYD is often used in combination with Mifepristone in UL treatment with satisfactory therapeutic effects,[14–16]
2 Methods
2.1 Protocol register
This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). Moreover, it has been registered on open science framework (OSF) (Registration number: DOI 10.17605/OSF.IO/YADN3).
2.2 Ethics
Ethical approval is not required for this study since it relies on secondary data.
2.3 Inclusion and exclusion criteria
The inclusion criteria of our review specified that: all participants in the included studies were patients with confirmed UL, without any restrictions concerning age and race; the treatment method in the intervention group was XFZYD combined with Mifepristone, while the treatment method in the control group was Mifepristone alone; all included studies were RCTs; and studies were from articles published in Chinese or English.
Exclusion criteria ruled out any studies that: displayed a lack of literature on related outcome indicators; had been selected for duplicate published studies; was impossible to extract the related data from the published results, and unable to obtain the primary data after contacting the author; the treatment group adopted other traditional Chinese medicine therapies, such as acupuncture and moxibustion, or other traditional Chinese medicine, the control group was not treated with Mifepristone alone.
2.4 Outcome measures
The primary outcomes included the effective rate, uterine leiomyoma volume (ULV, cm3 ), and uterine volume (UV, cm3 ). The secondary outcomes included the total incidence of adverse events (%), the incidence of estradiol (E2, pmol/L), luteinizing hormone (LH, IU/L), follicle-stimulating hormone (FSH, IU/L), and progesterone (P, nmol/L).
2.5 Search strategy
We searched for randomized controlled trials (RCTs) reported through December 2020; the electronic databases included: the Cochrane Library, PubMed, Embase, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and the Wanfang database. As a herbal formula of traditional Chinese medicine, XFZYD is mainly used in China, so the 4 electronic databases of China were searched to obtain a comprehensive study.
The keywords used, respectively, or in combination, to retrieve relevant published studies from 7 electronic databases included: “Xuefu Zhuyu Decoction ,” “Xuefu Zhuyu,” “uterine leiomyoma,” “uterine fibroids,” and so on. This retrieval strategy was determined after multiple searches. PubMed retrieval strategies are shown in Table 1 . The aim was to locate RCTs of XFZYD in combination with Mifepristone for the treatment of UL, filter documents, and extract data according to inclusion and exclusion criteria.
Table 1 -
Search strategy in PubMed database.
Number
Search terms
#1
Uterine leiomyoma [MeSH]
#2
Uterine fibroids [Title/Abstract]
#3
Fibroma, Uterine [Title/Abstract]
#4
Fibroid, Uterine [Title/Abstract]
#5
Leiomyoma, Uterine [Title/Abstract]
#6
Tumors, Fibroid [Title/Abstract]
#7
Fibroid Uterus [Title/Abstract]
#8
#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7
#9
Xuefu Zhuyu [Title/Abstract]
#10
XFZY [Title/Abstract]
#11
#9 OR #10
#12
#8 And #11
2.6 Study selection and data extraction
The 2 reviewers (SS, QY) read the title and abstract of the article independently, and then read the full text after screening to determine whether the final article should be included. Any differences were resolved by consensus or in consultation with a third party (FP). The integration process was shown as a flow diagram (Fig. 1 ). The data was extracted and managed by the 2 reviewers. The data collection form was designed in advance, and each reviewer independently extracted and collected data from the articles involved, including general trial characteristics (title, author, year); baseline data (sample size, age, sex, disease course); intervention measures (Chinese patent medicine dose, control intervention medication, intervention time); results (primary outcome indicators, secondary outcome indicators, adverse events). If there was a difference in perspective between the 2 reviewers, it was settled through negotiation or with assistance from a third party (FP).
Figure 1: Flow diagram.
2.7 Quality assessment
The 2 reviewers assessed the quality of the included study using the risk of bias tool recommended by the Cochrane collaboration. The risk of bias assessment was divided into 6 items, according to the Cochrane Handbook: random sequence generation; concealed allocation; blind implementation of participants and personnel; blind method of outcome assessment; incomplete result data; selective reporting, and other sources of bias. Each project had 3 categories: “high risk,” “low risk,” and “unclear.” Other deviations include profit deviations and sample calculations. In the case of inconsistency, the 2 reviewers negotiated between themselves or with a third party to resolve the difference.
2.8 Statistical analysis
This systematic review used Review Manager RevMan 5.3(developed by the UK's International Cochrane Collaboration) software (to analyze the data and I 2 I 2 < 50%, the heterogeneity between the 2 was considered acceptable, and a fixed-effect model was adopted. If I 2
2.9 Subgroup and sensitivity analyses
Subgroup analysis focused on the effect of different intervention characteristics on the cure rate, such as the duration of treatment, variance in the dosage of agents, and so on. A sensitivity analysis was performed to verify the stability of the results. After each document was excluded, the new results were analyzed again and compared with the original consolidated results to see if the study had affected the stability of the results.
2.10 Assessment of reporting bias
For the significant outcome indicators, a funnel plot was used to qualitatively detect publication bias when the number of the included study was ≥10. Egger and Begg tests were used to assess potential publication bias quantitatively.
2.11 Evidence quality evaluation
We grade the outcome indicators through the Grading of Recommendation Assessment, Development and Evaluation (GRADE) method.[17]
3 Discussion
As the incidence of UL increases, the cost of treatment plays a vital role in the world's health and economic burden.[18] [19] [20]
The TCM compound XFZYD is one of the decoctions commonly used in the clinical treatment of UL. The formula has the therapeutic properties of promoting blood circulation, removing blood stasis, and alleviating pain; these functions have been widely recognized in China.[21] Xuefu Zhuyu Decoction , has obvious inhibitory effect on the growth and proliferation of uterine fibroids;[22] [23] [24]
Although a number of clinical studies have confirmed the efficacy and safety of Xuefu Zhuyu Decoction combined with mifepristone in the treatment of uterine fibroids, the methods and results of various studies are different. Therefore, based on the current evidence, this study will evaluate the effectiveness of Xuefu Zhuyu Decoction combined with mifepristone in the treatment of uterine fibroids, providing a clinical basis for the clinical application of this treatment regimen.
However, this system evaluation has some limitations. There may be some clinical heterogeneity due to different drug doses, dosage forms, and patients’ disease degrees among the included studies. Due to the different follow-up time of different studies, there are differences in the evaluation of long-term efficacy and safety. Due to the limitation of language retrieval, we will only include Chinese and English literature, and may ignore studies in other languages and regions.
Author contributions
Administrative support: Shasha Shi.
Collection and assembly of data: Shasha Shi, Qiaobo Ye.
Conception and design: Chenghao Yu.
Conceptualization: Chenghao Yu.
Data analysis and interpretation: Shasha Shi, Qiaobo Ye.
Data curation: Shasha Shi, Qiaobo Ye.
Final approval of manuscript: Shasha Shi, Qiaobo Ye, Chenghao Yu, Fu Peng.
Manuscript writing: Shasha Shi, Fu Peng.
Provision of study materials or patients: None.
Resources: Qiaobo Ye.
Writing – original draft: Shasha Shi, Fu Peng.
Writing – review & editing: Shasha Shi, Qiaobo Ye, Fu Peng.
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