1 Introduction
Irregular menstruation, a common gynecological disease, mainly refers to the syndrome of abnormal menstrual cycle or menstrual period, which is more common in adolescent or menopausal women.[1,2]
The etiology and pathogenesis of irregular menstruation are complex. The clear etiology is the endocrine dysfunction of reproductive nerve to cause abnormal uterine bleeding. Insufficient progesterone secretion or premature decline of corpus luteum in corpus luteum stage could lead to poor endometrial secretion reaction, or the prolonged corpus luteum atrophy cycle may result in irregular shedding of endometrium. In modern medicine, the mostly used therapy is hormone.[3–5]
Acupuncture therapy has been widely used in the treatment of female gynecological diseases in recent years. Acupuncture could promote the recovery of menstrual cycle through acupoint selection and manipulation. The implementation of acupuncture artificial cycle therapy according to the change of female menstrual cycle can achieve remarkable results.[6–8]
However, there are various acupuncture therapy applied for patients with irregular menstruation, such as filiform needles, electroacupuncture, scalp acupuncture, and acupuncture combined with medications, and the efficacy are different in many studies. A network meta-analysis could be feasible to assess the efficacy and safety of various acupuncture for irregular menstruation. Therefore, we try to conduct a Bayesian network meta-analysis to evaluate the efficacy and safety of various acupuncture in the treatment of irregular menstruation.
2 Methods
This protocol of Bayesian network meta-analysis is drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols.[9]
2.1 Eligible criteria
2.1.1 Type of studies
Randomized controlled trials (RCTs) of acupuncture in the treatment of irregular menstruation will be included, and languages are limited to Chinese and English. Studies with unsatisfactory outcome indicators, unable to extracting data, incorrect random methods will be excluded.
2.1.2 Type of participants
All the included cases conform to the diagnosis of irregular menstruation, regardless of nationality, race, age, gender, and source of cases.
2.1.3 Type of interventions
The study focuses on RCTs of irregular menstruation treated by any acupuncture therapies, including filiform acupuncture, fire needle acupuncture, electro-acupuncture, acupoint injection, and auricular acupuncture, with completely and precisely described point prescriptions. The intervention in the control group will not be limited.
2.1.4 Type of outcome measures
The primary outcome is the efficacy of irregular menstruation, and the secondary outcomes include serum estradiol 2, progesterone, follicular estrogen, luteinizing hormone, endometrial thickness, and the incidences of adverse events related to the interventions, such as allergy, infection, coughing, and nausea.
2.2 Literature sources and search strategy
A comprehensive literature search will be conducted in both English and Chinese database, including Medline, PubMed, Embase, Cochrane Library, Wanfang, China National Knowledge Infrastructure, Chongqing VIP Database, and Chinese Biological and Medical database, from inception to October 2021. MeSH terms and key words will be used to identify RCTs of acupuncture against irregular menstruation, with the following terms and combinations: “irregular menstruation,” “menstruation disturbances,” “menstrual irregularities,” “irregular menses” “electroacupuncture,” “acupuncture,” “acupoint injection,” “auricular acupuncture,” “fire needle acupuncture,” etc. The search strategy of PubMed is listed in Table 1 .
Table 1 -
Search strategy in PubMed.
Number
Search terms
#1
Randomized controlled trial [Publication Type]
#2
Controlled clinical trial [MeSH Terms] OR Randomized [Title/Abstract] OR Clinical trials as topic [MeSH Terms] OR Randomized controlled trial [Title/Abstract] OR Random allocation [MeSH Terms]
#3
#1 OR #2
#4
Irregular menstruation [MeSH Terms]
#5
Menstruation disturbances [Title/Abstract] OR menstrual irregularities [Title/Abstract] OR irregular menses OR Hypomenorrhea [Title/Abstract] OR Polymenorrhea [Title/Abstract] OR Menstruation Disorder[Title/Abstract]
#6
#4 OR #5
#7
Acupuncture therapy [MeSH Terms]
#8
Acupuncture [MeSH Terms]
#9
Acupuncture therapy [Title/Abstract] OR Acupuncture [Title/Abstract] OR Acupoints [Title/Abstract] OR Acupuncture [Title/Abstract] OR Filiform acupuncture [Title/Abstract] OR Fire needle acupuncture [Title/Abstract] OR Manual acupuncture [Title/Abstract] OR Auricular acupuncture [Title/Abstract] OR Ear acupuncture [Title/Abstract] OR Electroacupuncture [Title/Abstract] OR Fire needle [Title/Abstract] OR Scalp needle [Title/Abstract] OR Abdominal acupuncture [Title/Abstract] OR Transcutaneous electrical stimulation [Title/Abstract] OR Acupoint injection [Title/Abstract]
#10
#7 OR #8 OR #9
#11
#3 AND #6 AND #10
2.3 Literature screen and data extraction
The study screen process will follow the preferred reporting items for systematic reviews and meta-analyses guidelines (Fig. 1 ). Endnote X9 will be applied to remove duplicate. Two authors will independently read the titles, abstracts, and full text, and screen the literature according to the eligible criteria. Then the two researchers will crosscheck the included literature. For documents that are difficult to determine, the decision will be made by discussion. Finally, literature title, first author, journal, publication year, participants’ age, sample size, sex ratio, randomization, concealment, types of interventions, outcomes, adverse events from the eligible RCT studies will be extracted. Two authors will independently extract the information, and if there is any disagreement, the decision will be made by discussion.
Figure 1: Flow diagram.
2.4 Risk of bias assessment
The risk of bias assessment will be performed in accordance with the Cochrane Handbook, including random sequence generation, allocation concealment, blinding, integrity of outcome data, follow-up, selecting report, and other bias. The final risk of bias of studies is of bias. According to the design and implementation of original literature, the bias will be classified as high, unclear or low risk. Two independent reviewers will conduct the assessment, and third researcher will be consulted to make a final decision.
2.5 Statistical analysis
2.5.1 Pairwise meta-analysis
RevMan 5.3 software provided by the Cochrane Collaboration will be used for pairwise meta-analysis. For dichotomous variables, the odds ratio will be used as effect indicator, and mean difference for the continuous variable, with a 95% Confidence interval. Heterogeneity will be assessed by I -square (I 2 ), and P < .1 is considered as inter-study heterogeneity. If I 2 I 2
2.5.2 Network meta-analysis
ADDIS 1.16.8, Open BUGS 3.2.3, and Stata 14.0 will be performed. For dichotomous data, odds ratio and 95% confidence interval will be applied. ADDIS 1.16.8 will be applied for the variance of chains by adopting convergence evaluated by potential scale reduced factor, and potential scale reduced factor closed to 1 indicating a good convergence with a high reliability results. Node spilt analysis will be used for inconsistencies between direct and indirect comparisons. When P > .05 in node spilt analysis, the consistent model will be selected; otherwise, the inconsistent model will be selected. The surface under the cumulative ranking curve will be sued for carrying out a possible range of interventions by Open BUGS 3.2.3, from 0 to 100%, and a higher surface under the cumulative ranking curve value indicating a better intervention effect.
2.5.3 Subgroup analysis
If the heterogeneity is large, a subgroup analysis will be conducted. The sensitivity analysis will be performed by a one-by-one elimination method.
2.5.4 Reporting bias
If the included studies are larger than 10, a comparison-adjusted funnel plot will be used to assess publication bias.
2.5.5 Quality evaluation
The Grading of Recommendations Assessment, Development, and Evaluation will be applied d to assess the quality of evidence, as divided in to high, moderate, low, and very low.
3 Discussion
A normal menstrual cycle ranges from 21 to 35 days for most women. However, many women are likely to experience an irregular menstrual cycles, such as amenorrhea, oligomenorrhea, menorrhagia, prolonged menstrual bleeding, or dysmenorrhea. Mostly, irregular menstruation can be caused by an imbalance of hormones, particularly estrogen and progesterone. The ongoing irregular menstruation can make it difficult to conceive and the negative effects may influence the normal life and work of patients.
Acupuncture is often widely used to relieve pain in many studies.[10–12] [13,14] network meta-analysis to evaluate the efficacy and safety of various acupuncture in the treatment of irregular menstruation. Yet, there still might be several limitations in the protocol, including the limited literature languages, various acupoint selections to lead to bias. Subgroup analysis, if possible, will be applied to minimize it.
Author contributions
Data collection: Junting Wang and Heran Zhang.
Funding support: Heran Zhang.
Literature retrieval: Junting Wang and Heran Zhang.
Software operating: Heran Zhang.
Supervision: Heran Zhang.
Writing – original draft: Junting Wang and Heran Zhang.
Writing – review & editing: Heran Zhang.
References
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[4]. Roomruangwong C, Sirivichayakul S, Matsumoto AK, et al. Menstruation distress is strongly associated with hormone-immune-metabolic biomarkers. J Psychosom Res 2021;142:110355.
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[12]. Liu LY, Tian ZL, Zhu FT, et al. Systematic review and meta-analysis of acupuncture for pain management in women undergoing transvaginal oocyte retrieval. J Pain Res 2021;14:2833–49.
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