Shu-Cheng Chen1
Jia-Yin Ruan1
Bohan Zhang1
Lok-Yi Pang1
Linda Zhong2Shuang-Lan Lin1
Ka-Po Wong3Hui-Xi Ouyang4
Wing-Fai Yeung1
Qin-Wei Fu5*
Bo-Qian Chen6*- 1School of Nursing, Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- 2School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- 3Department of Applied Social Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- 4The Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- 5Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- 6Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD).
Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions.
Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = −1.51, 95%CI (−2.91, −0.12)/SMD = −2.31, 95%CI (−4.61, −0.02)], warm needling [SMD = −1.43, 95%CI (−2.68, −0.18)/SMD = −2.23, 95%CI (−4.43, −0.03)], moxibustion [SMD = −1.21, 95%CI (−1.85, −0.57)/SMD = −2.10, 95%CI (−3.95, −0.07)], and acupuncture [SMD = −1.09, 95%CI (−1.62, −0.55)/SMD = −1.89, 95%CI (−3.67, −0.11)]. No adverse events were detected.
Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network.
Systematic review registration: PROSPERO CRD42022373312.
1 Introduction
Primary dysmenorrhea (PD) refers to the occurrence of menstrual cramps in the lower abdomen, without any identifiable pelvic pathology, with characteristic symptoms such as lower abdominal or pelvic pain, ranging from 8 h to 72 h and typically occurring at the onset of menstrual flow (1). Other associated symptoms include low back pain, headache, diarrhea, fatigue, nausea, or vomiting (2). The prevalence of PD varies from 50 to 90% (3). The exact causes remain unknown, leading to non-targeted treatments. Risk factors for PD include early age at menarche, heavy menstrual flow, nulliparity, family history of dysmenorrhea, and stress (4).
Systematic reviews and randomized controlled trials (RCTs) have shown that non-steroidal anti-inflammatory drugs (NSAIDs) (5, 6) and hormonal regulation through oral contraception (7) are significantly more effective for pain relief than placebo, and they are often used for symptom control (8). However, some women may not always find them effective or acceptable; for example, NSAIDs have undesirable side effects (6). Non-drug, non-surgical treatments for PD include transcutaneous electric nerve stimulation, behavior modification/relaxation, acupressure, acupuncture, spinal manipulation, topical heat, vitamin E, thiamine, fish oil, and herbal medicine (9). Only 26.7% of patients with PD have no experience with complementary and alternative medicine. Diet and homeopathy are the most frequently used methods from complementary and alternative medicine. In spite of the provision of information on efficacy, safety, and costs, patients choose methods based on earlier experience (10). Despite their popularity, evidence on the effectiveness of these nonpharmacologic therapies for PD is limited and inconsistent (11, 12).
Traditional Chinese medicine (TCM) interventions based on meridian theory can be an effective alternative approach for PD. Meridian is a system of conduits through which qi and blood circulate, connecting the bowels, viscera, extremities, superficial, organs, and tissues and making the body an organic whole. The meridian system includes 12 regular meridians, 8 extra meridians, 12 meridian divergence, 12 meridian sinews, 12 cutaneous vessels, and 15 collateral vessels (13). Meridian-based TCM interventions include acupuncture, acupressure, tuina, moxibustion, cupping, auricular therapy, electro-acupuncture, and scraping. These interventions may produce analgesic effects through the regulation of the hypothalamic–pituitary–ovarian axis, modulation of the immune system, and release of endogenous opioid peptides (14). Animal experiments have demonstrated that acupuncture may facilitate the release of central and peripheral neurotransmitters, modulation of immune function, and alleviation of uterine smooth muscle spasm (15, 16). Clinical trials have indicated that acupuncture may elicit analgesia by regulating serum levels of prostaglandins and ovarian hormones, facilitating the release of peripheral β-endorphin, improving the status of uterine artery blood flow, and alleviating uterine smooth muscle spasm (14). Similarly, moxibustion may modulate endocrine hormones, immune function, and nerve factors and enhance uterine microcirculation (17).
Numerous studies have investigated the efficacy of TCM interventions based on meridian theory for dysmenorrhea, including systematic reviews, RCTs, and case series. A systematic review of RCTs on acupuncture for PD reported that acupuncture provides superior pain relief (OR: 4.99; 95% CI: 2.82–8.82; 4 RCTs; I2 = 0%) and has fewer adverse events compared with NSAIDs (OR: 0.10; 95% CI: 0.02–0.44; 4 RCTs; I2 = 15%); however, evidence quality was low, and further research is needed to ascertain the effectiveness of acupuncture and acupressure (18). In an RCT of 152 subjects, moxibustion was found to have sustained and superior pain-relieving effects compared with drugs 3 months post-intervention (effect size: −0.87, 95% CI: −1.32 to −0.42, p < 0.001) measured by the visual analogue scale (VAS) (19). Acupressure on the SP6 meridian was found to be superior to placebo acupressure in relieving PD pain symptoms based on a VAS score (−4.935; 95% CI: [−15.757, 5.887]; p = 0.371) (20), whereas auricular therapy was found to be more effective than analgesics based on VAS scores (OR = 3.28, 95%CI: [1.37, 7.85], p = 0.008) (21). Although numerous studies have examined the effects of meridian-based TCM interventions for PD pain, no comparative analysis of their effectiveness has been conducted. Therefore, a comprehensive comparison of multiple TCM interventions based on meridian theory is required, as well as organization and collection of high-quality evidence.
Network meta-analysis (NMA) yields high-quality evidence, which can be used to evaluate the effects of multiple interventions and rank optimal intervention strategies (22). This study performed an NMA of RCTs on TCM interventions based on meridian theory for relieving pain in patients with PD, comparing the effects among interventions (TCM interventions based on meridian theory and eligible control interventions), and exploring the optimal one. The findings can provide evidence to help clinical workers and researchers understand the optimal protocol for pain management of PD.
2 Methods
This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) (18), the PRISMA-2020 guidelines (19), and the extension statement for network meta-analysis (PRISMA-NMA) (20). The protocol was registered on PROSPERO (CRD42022373312).
2.1 Selection criteria
Studies had to fulfill the following criteria presented in PICOS tools (population, intervention, comparators, outcomes, and study design): (1) population: patients diagnosed with PD; (2) intervention: meridian-based TCM interventions including acupressure, acupuncture, moxibustion, tuina, electroacupuncture, warm needling, auricular therapy, and scraping therapy (Interventions should be singly used, so that their effects can be detected. Interventions related to Chinese herb, staging acupoint catgut embedment therapy, acupuncture point injection therapy, or combined TCM intervention were excluded.); (3) comparators: control group with waitlist, placebo, western medicine (e.g., NSAIDs and combined oral contraceptives), conventional therapy, or another type of meridian-based TCM interventions (Studies comparing two or more meridian-based TCM interventions were included. Usual care was excluded due to the variety of care content among different interventions and study settings.); (4) outcomes: studies that evaluated pain intensity using VAS or numerical rating scale (NRS); and (5) study design: RCTs.
2.2 Search strategy
We searched Ovid MEDLINE, Embase, Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, Web of Science, Allied and Complementary Medicine, the China National Knowledge Infrastructure, Wanfang Data, PubMed, SinoMed, and CQVIP from database inception until 1 July 2023. The following keywords were used for our search: (massag* OR anmo OR acupress* OR tuina OR acupunct* OR electroacupunct* OR electro-acupunct* OR acupoint* OR meridia* OR auricular OR needl* OR moxibustion OR moxa) AND (dysmenorr* OR menstrua* pain OR period cramp OR period pain* OR menstrua* distress OR period distress OR menstrua* distress). To search the Chinese databases, we used the corresponding Chinese keywords. We did not impose any language restrictions (See Supplementary Appendix 1). We also scanned reference lists of relevant systematic reviews and clinical guidelines. Two authors (SCC and JYR) independently performed the literature search. Disagreements were resolved upon consultation and judgement by a third reviewer (WFY).
2.3 Data extraction
Two authors (SSC and LYP) independently screened the titles and abstracts of the retrieved studies, and the unrelated articles were removed. Thereafter, we reviewed the full texts of potentially relevant studies and extracted the data based on the selection criteria. The following data were extracted from the included RCTs in a predesigned data sheet: the first author’s name, publication year, characteristics of participants, sample size, diagnostic system, details of interventions, details of the control interventions, follow-up period, details of outcomes, and language. Basic information on the excluded studies was also extracted to provide a comprehensive reference to readers, with information on the original title, publication year, and reasons for exclusion. An additional reviewer (WFY) was consulted in the event of discrepancies between authors.
2.4 Quality assessment
Two authors (SCC and LYP) performed the quality evaluation of included studies independently in accordance with Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (21). The risk of bias for trials was assessed using criteria in the Cochrane Risk of Bias version 2 (RoB 2) tool. We assessed potential bias related to five domains, namely, randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Each publication was identified as “high risk,” “low risk,” or “some concerns.” If there were any objections, they would be discussed or judged by a third researcher (WFY) to reach a consensus.
The GRADEpro Guideline Development Tool web page was employed to assess the evidence for the quality of outcome indicators including five degrading factors: risk of bias, inconsistency, indirectness, imprecision, and publication bias (23). On the basis of these variables, the software generates a GRADE rating of “high,” “moderate,” “low,” or “very low” to reflect the certainty of the reported effect. A summary of findings (SoF) table was generated for a given comparison of interventions to provide key information concerning the magnitudes of relative and absolute effects of the interventions examined, the amount of available evidence, and the quality of available evidence (21).
2.5 Statistical analysis
Standard mean difference (SMD) with a 95% confidence interval (CI) was used to estimate the effect sizes of NRS or VAS. Variation was expected between the original studies. To make the results more conservative, a random effects model was used rather than a fixed effects model. The statistical heterogeneity in each pairwise comparison was assessed using inconsistency index tests or Chi-square test or I2 statistic test (I2 > 30% or p-value <0.1 indicating inconsistency). Additionally, sensitivity analysis was conducted to verify the robustness of the results and test the source of heterogeneity in each RCT. Three-armed RCTs were transformed into two-armed pairs to clearly present the effects of comparisons. For the studies that reported the mean and standard deviation of effect changes in the interventions, we calculated the data at the endpoint of the intervention period using the current data.
An NMA with a Bayesian framework using Statistics and Data Science (STATA) software was conducted to assess the outcomes of different interventions (24). Network diagrams were used to present the results: (1) each node represents an exercise intervention; (2) the size of the node indicates the sample size of the subjects who performed this intervention; (3) if there are no line segments between each node, then indirect comparisons will be made between the nodes; if there are line segments, then direct comparisons will be made between the nodes; (4) the thickness of the line segments between the nodes indicates the original study sample size; and (5) the size of the nodes and the thickness of the line segments are positively correlated with the number (25). The surface under the cumulative ranking curve (SUCRA) is the probability each intervention has of being among the best of those in the network; the SUCRA values range from 0 to 1, with large values representing high intervention ranking probabilities (26). NMA results were visualized using forest plots. A funnel plot was generated to examine possible publication bias.
3 Results
3.1 Literature search
Our search yielded a total of 3,080 potentially eligible citations, among which 704 remained after the removal of duplicates and irrelevant records. Of the remaining citations, 86 studies were obtained by reading the titles and abstracts. After the full text of these records was screened, 57 studies were included for network analysis. The PRISMA flow diagram describing the inclusion process is presented in Figure 1. Supplementary Appendix 2 shows the details of the excluded studies from full-text screening.
Figure 1. PRISMA Flow Chart.
3.2 Description of included studies
As shown in Table 1, the included 57 RCTs were published between 2011 and 2022 and included 3,903 participants. The included participants’ age ranged from 14 years to 39 years. The sample size of the included RCTs was from 20 to 208. Besides the eligibility on age, disease duration, and intervention use records, most RCTs screened and included participants by using pain rating scales (57 studies), including VAS and NRS. Eight types of meridian-based TCM interventions were reported among the included RCTs, namely, acupuncture (n = 865) (31, 32, 35–37, 41, 44, 46, 50–56, 58, 62–65, 68, 70), acupressure (n = 285) (27, 28, 30, 33, 34, 71, 72, 79), auricular therapy (n = 35) (57), electro-acupuncture (n = 66) (34, 47), moxibustion (n = 651) (29, 38–40, 42–44, 48–50, 61, 62, 66, 67, 74, 77), scraping therapy (n = 30) (69), tuina (n = 57) (45, 54), and warm needling (n = 151) (41, 59, 60, 78). The most commonly involved meridians included conception vessel (CV), spleen meridian (SP), stomach meridian (ST), and governor vessel (GV). Four types of control interventions were reported, namely, health education (27), waitlist (35, 81), placebo (sham interventions) (28–30, 32, 33, 56, 72, 82), and conventional medicine (oral contraceptive pill and NSAIDs) (31, 36–40, 42, 43, 45–49, 51–53, 55, 57–61, 63–71, 73–80, 83). Pain outcome measures included VAS and NRS. One RCT used both VAS and NRS (29), 3 used NRS only (36, 59, 69), and the other 53 used VAS only. The treatment period ranged from 30 min to 3 months, and the follow-up period ranged from 3 h to 6 months. Twelve RCTs were published in English and 45 were in Chinese.
Table 1. Characteristics of the included studies.
3.3 Risk of bias
Figure 2 presents a summary of the methodological quality of the included studies. Thirty-two RCTs were rated as low risk of bias (28, 31, 33, 34, 36, 39–43, 46, 47, 49, 51, 56, 59, 61–66). Nineteen studies were rated as high risk of bias due to the application of inappropriate data analysis methods (27, 29, 30, 32, 45, 48, 50, 54, 55, 57, 58, 60, 68, 71, 72, 81, 83) or unblinding of the outcome assessors (35, 81). The remaining six studies were rated as having certain concerns because of the insufficient information on data analysis methods (37, 38, 44, 52, 53, 77) or the high dropout rate (57, 75).
Figure 2. Summary of risk of bias (RoB) of the included studies.
3.4 Network diagram
A network diagram was drawn based on 15 interventions, including 3,903 participants. A total of 105 pairs of comparisons were formed (including 18 pairs of direct comparisons and 87 pairs of indirect comparisons). Nineteen RCTs reported a comparison between acupuncture and NSAIDs, and 12 RCTs reported the comparison between moxibustion and NSAIDs. Direct comparisons between 9 pairs of comparisons occurred only once. Among these interventions, NSAIDs had the largest sample size (n = 1,426), followed by acupuncture (n = 865), moxibustion (n = 651), and warm needling (n = 151). The data are shown in Figure 3. (Supplementary Appendix 3).
Figure 3. A network diagram for all interventions.
3.5 Heterogeneity and inconsistency test
Conceptual heterogeneity and inconsistency were low across the network given that all the included studies had the same study design, participants, and outcomes. Statistical heterogeneity was high in several pairwise comparisons (Supplementary Appendix 4). Supplementary Appendix 5 shows the detailed information on the local inconsistency test. A node-splitting test was conducted for local inconsistency analysis, and 19 pairs of mixed comparisons (including direct and indirect) were analyzed. The results showed no statistical inconsistency in each pair of direct comparison. Sensitivity analysis indicated that the findings were robust (Supplementary Appendix 6).
3.6 NMA
As shown in Figure 4, the estimated effect of the NMA for each intervention on relieving PD pain was generated. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = −1.51, 95% CI (−2.91, −0.12)/SMD = −2.31, 95% CI (−4.61, −0.02)], warm needling [SMD = −1.43, 95% CI (−2.68, −0.18)/SMD = −2.23, 95% CI (−4.43, −0.03)], moxibustion [SMD = −1.21, 95% CI (−1.85, −0.57)/SMD = −2.10, 95% CI (−3.95, −0.07)], and acupuncture [SMD = −1.09, 95% CI (−1.62, −0.55)/SMD = −1.89, 95% CI (−3.67, −0.11)].
Figure 4. The network meta-analysis for all interventions.
3.7 Probability ranking
Figure 5 shows the SUCRA probability ranking for the different treatment effects of all interventions. For the 15 interventions, the SUCRA value predicted the possibility of different interventions as the best treatment on the management of PD pain, and the ranking was as follows: oral contraceptive pill (75.8%), electro-acupuncture (73.0%), acupressure (72.9%), warm needling (70.6%), moxibustion (64.9%), acupuncture (60.0%), health education (59.7%), tuina (52.3%), scarping therapy (48.0%), sham moxibustion (43.1%), sham acupressure (34.8%), auricular therapy (34.1%), sham acupuncture (24.9%), NSAIDs (23.9%), and waitlist (12.1%).
Figure 5. The probability ranking for all the interventions.
3.8 Safety
Information on the safety of different interventions was collected and assessed based on adverse events reported in RCTs. Nineteen RCTs reported adverse events on acupuncture, warm needling, NSAIDs, and sham acupressure. For acupuncture and warm needling, adverse events included local bleeding or hematoncus (8 RCTs) (36, 37, 51, 53, 58, 60, 68, 73), headache or myalgia (1 RCT) (36), fever (1 RCT) (36), nausea (1 RCT) (46), and nervousness in the first treatment session (1 RCT) (71). Adverse events of NSAIDs incorporated gastrointestinal symptoms (13 RCTs) (36, 37, 46, 48, 51–53, 65, 68, 69, 73, 75, 83), vaginal bleeding (1 RCT) (36), weight gain (1 RCT) (36), breast engorgement (1 RCT) (36), hypermenorrhea (1 RCT) (48), rash (1 RCT) (52), and dizziness and tinnitus (3 RCTs) (68, 73, 83). An RCT also reported that the analgesic effect of medication faded away with repetitive use in some cases (31). An RCT mentioned that 3 participants dropped out from the sham acupressure control group due to severe pain (30, 72), whereas another RCT reported that 2 participants dropped out from the sham acupressure group without providing the specific reasons (30). Details on the adverse events of the interventions are in Supplementary Appendix 7.
3.9 Certainty of evidence
The evidence quality of all 18 comparisons was evaluated by GRADEpro. High-quality evidence was found in two comparisons on PD pain symptoms, namely, acupuncture versus placebo and electroacupuncture versus NSAIDs. The evidence quality was evaluated as moderate in six comparisons: acupressure versus placebo, moxibustion versus NSAIDs, moxibustion versus acupuncture, tunia versus acupuncture, warm needling versus NSAIDs, and scraping therapy versus NSAIDs. The evidence quality of the rest of the 10 comparisons was evaluated as low or very low. The most common reason for downgrading the evidence quality was imprecision, followed by high heterogeneity and high risk of bias. Details of the SoF table are in Supplementary Appendix 8.
3.10 Publication bias
The publication bias is shown in Appendix 9. The results showed that the studies were roughly symmetrical around the center line. Egger’s test (p = 0.162) showed no significant risk of publication bias as well.
4 Discussion
Numerous clinical trials and systematic reviews have investigated the effects of meridian-based TCM interventions for PD pain and suggested that these interventions can reduce PD pain intensity, duration, and related symptoms, with relatively few adverse events. However, this work is the first study to quantitatively summarize and compare the effects of the meridian-based TCM interventions via NMA. In PD pain management, the effects of acupressure, acupuncture, and moxibustion were superior to those of NSAIDs and waitlist; acupressure was more effective than placebo; and warm needling was superior to both NSAIDs and waitlist.
Previous reviews have evaluated the effects of meridian-based TCM interventions for PD pain and found similar results to this study. A systematic review of acupuncture-related therapies (acupuncture, acupoint injection, acupressure, and moxibustion) for PD indicated that acupuncture was significantly more effective than placebo (WMD = −0.57, 95% CI [−0.76, −0.38]) and NSAIDs (WMD = −0.19, 95% CI [−0.37, −0.01]) in PD pain management, and acupressure was more effective than placebo (WMD = −0.91, 95% CI [−1.78, −0.04]). Nevertheless, the reliability of their review may be compromised because it included a combination of randomized and non-randomized trials with fewer interventions, trials, and comparisons. Moreover, most of the studies included were deemed low in methodology (84). Another systematic review on the effects and safety of acupuncture and moxibustion for PD demonstrated that acupuncture (MD = −1.93; 95% CI [−2.80, −1.06]) and moxibustion (MD = −2.67; 95% CI [−4.96, −0.38]) are more effective in managing PD pain than the control via VAS; however, the review combined all control interventions as one for their meta-analysis (85). Similarly, Jiang et al. conducted a systematic review of RCTs on acupressure for PD and reported that acupressure is better at improving pain with VAS compared with placebo or waitlist (MD: −1.41, 95% CI [−1.61, −1.21]), but the study found no difference in pain relief between acupressure and NSAIDs. This discrepancy may be due to the small number of RCTs with modest sample included, which hindered the detection of treatment effects in their systematic review (86). The present study’s findings suggested that electroacupuncture may be an optimal intervention strategy for PD pain; however, direct comparisons among interventions were few based on a limited number of studies.
For safety issues, the current study provided evidence that meridian-based TCM interventions are safe with no severe adverse events for the treatment of PD, and the reported adverse events focused on acupuncture and warm needling. These results were in accordance with previous studies (33, 84, 85). Fainting, hematoma or bleeding, sticking of needle, and needling sensation after acupuncture are common situations during acupuncture treatment in clinics or research (87). These situations might be related to irregular acupressure practice of practitioners, participants’ mental and physical conditions, and participant–practitioner interactions (88). All the abovementioned adverse events are mild and can be handled well under appropriate management. A systematic review examining the adverse events of meridian-based TCM interventions between 2000 and 2011 (117 studies, 25 countries, and 294 cases with adverse events in acupuncture) emphasized the significance of acupuncture practice guidelines (89). Therefore, to minimize adverse events, practitioners should strictly follow the operation guidelines, observe the situation of patients, and communicate with them actively during acupuncture treatment. Standard reporting form can be adopted in future studies to systematically document the occurrence and severity of AE (90).
The good statistical consistency observed in the NMA suggested that the variation in the treatment effects of the meridian-based TCM interventions is predictable and not due to chance (91). However, the statistical heterogeneity in the pairwise comparisons within the NMA is high. Several appropriate statistical methods were applied to identify the sources of heterogeneity. Sensitivity analysis indicated the robustness of the overall results of the meta-analysis (92). Publication bias was suggested from the funnel plot and Egger’s test. Considering that the overall methodological quality of the included studies was high, the high statistical heterogeneity observed in the pairwise comparisons could be attributed to the variability in sample size or the different durations of intervention among various studies (93). The heterogeneity may also arise from differences in demographic characteristic of participants with PD among the study populations (94). Future systematic reviews may limit the age range of the participants, define the optimal information size (for example, 400 as suggested by GRADEpro handbook) (95), and set the treatment duration and frequency. Special attention should be paid to the clinical trials with a large effect size but a small sample size (96, 97).
For the quality of methodology of the included studies, factors that led to high risk of bias included the application of inappropriate data analysis methods, unblinding of the outcome assessors, insufficient information on data analysis methods, and high dropout rate. The factors that rated down the evidence quality of this study by GRADEpro contained imprecision, high heterogeneity, and risk of bias. Further RCTs should give particular emphasis on these several domains, applying the intention-to-treat approach for data analysis to eliminate or reduce bias in treatment effects arising from missing data (98), blinging the outcome assessors to reduce detection bias (99), reporting the results completely to avoid selective reporting bias (e.g., selective outcome reporting, selective analysis reporting, and lack of reporting of adverse events and dropout reasons) (100), and making sure that the sample size has the power to demonstrate the smallest effect of intervention (101).
4.1 Implication
The findings of this study can implicate PD patients, healthcare providers, researchers, and policy makers. The study provides a potential ranking of the effects of multiple interventions (e.g., meridian-based TCM interventions and conventional western medicine) for relieving PD pain, as well as their adverse events. The information could be a reference for PD patients when choosing interventions. Health care providers may use the findings to inform their clinical decisions and improve patient outcomes. Researchers may find some research gaps from the findings. For example, the results indicated that acupressure, moxibustion, and warm needling may also have significant effects on PD pain, but relevant evidence is very limited. More clinical trials can be conducted to examine their effects on PD pain management. Researchers could further explore the effects of meridian-based TCM interventions on other outcomes in patients with PD. Policy makers in the field of women’s health may focus on the safety and potential effects of meridian-based TCM interventions and highlight the importance of integrating these interventions into clinical practice guidelines and health care policies.
4.2 Strength
The present study has several strengths. First, the study strictly defined the inclusion criteria, and the overall methodological quality of the included studies was high. Second, we limited the outcome as PD pain, providing a clear and specific research question that allowed for a focused assessment of the current evidence. Third, evidence of both effects and adverse events was collected, enabling readers to obtain knowledge of meridian-based TCM interventions on PD pain. Additionally, the review included studies published in both English and Chinese, which increased the generalizability of the findings and avoided potential language bias.
4.3 Limitation
Several limitations of this study should be acknowledged. First, as a result of the diversity of intervention types, the number of studies using the same interventions in some direct comparisons was relatively small. Besides, the duration of the interventions varied across the included studies, which may affect the effects of the interventions. These factors may subsequently influence the reliability of the findings. Second, the study only focused on the severity of PD pain as the sole outcome. Evidence on the effects of meridian-related interventions on other associated symptoms such as menstrual blood flow, sleep quality, and mood was not reviewed. Lastly, the statistical heterogeneity observed among different comparisons was high, suggesting the presence of substantial variability in the results and limiting the generalizability of the findings.
5 Conclusion
For the management of PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Furthermore, based on probability ranking, oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. Meridian-based TCM interventions are safe, and no severe related adverse events were detected. More high-quality clinical trials are needed to provide more robust evidence of this NMA.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.
Author contributions
S-CC: Conceptualization, Formal analysis, Methodology, Writing – original draft. J-YR: Methodology, Writing – review & editing. BZ: Formal analysis, Writing – original draft. L-YP: Formal analysis, Writing – original draft. LZ: Writing – review & editing. S-LL: Formal analysis, Writing – original draft. K-PW: Writing – review & editing. H-XO: Writing – review & editing. W-FY: Writing – review & editing. Q-WF: Conceptualization, Writing – review & editing. B-QC: Writing – review & editing, Conceptualization.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Conflict of interest
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.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Publisher’s note
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Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2024.1453609/full#supplementary-material
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Keywords: primary dysmenorrhea, TCM, Chinese medicine, acupuncture, acupressure, moxibustion, tuina, warm needling
Citation: Chen S-C, Ruan J-Y, Zhang B, Pang L-Y, Zhong L, Lin S-L, Wong K-P, Ouyang H-X, Yeung W-F, Fu Q-W and Chen B-Q (2024) Traditional Chinese medicine interventions based on meridian theory for pain relief in patients with primary dysmenorrhea: a systematic review and network meta-analysis. Front. Med. 11:1453609. doi: 10.3389/fmed.2024.1453609
Edited by:
Cristina Secosan, Victor Babes University of Medicine and Pharmacy, RomaniaReviewed by:
Coroleuca Catalin, Clinical Hospital of Obstetrics and Gynecology Prof. Dr. Panait Sârbu, RomaniaRazvan Ciortea, County Emergency Hospital Cluj-Napoca, Romania
Copyright © 2024 Chen, Ruan, Zhang, Pang, Zhong, Lin, Wong, Ouyang, Yeung, Fu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Bo-Qian Chen, 20193113175@stu.gzucm.edu.cn; Qin-Wei Fu, fuqinweitcm@163.com