Objective A number of randomised controlled trials have been performed to determine the effectiveness or efficacy of acupuncture in primary dysmenorrhoea. The objective of this review was to explore the relationship between the ‘dose’ of the acupuncture intervention and menstrual pain outcomes.
Methods Eight databases were systematically searched for trials examining penetrating body acupuncture for primary dysmenorrhoea published in English up to September 2015. Dose components for each trial were extracted, assessed by the two authors and categorised by neurophysiological dose (number of needles, retention time and mode of stimulation), cumulative dose (total number and frequency of treatments), needle location and treatment timing.
Results Eleven trials were included. Components of acupuncture dose were well reported across all trials. The relationship between needle location and menstrual pain demonstrated conflicting results. Treatment before the menses appeared to produce greater reductions in pain than treatment starting at the onset of menses. A single needle during menses may provide greater pain reduction compared to multiple needles. Conversely, multiple needles before menses were superior to a single needle. Electroacupuncture may provide more rapid pain reduction compared to manual acupuncture but may not have a significantly different effect on overall menstrual pain.
Conclusions There appear to be relationships between treatment timing and mode of needle stimulation, and menstrual pain outcomes. Needle location, number of needles used and frequency of treatment show clear dose-response relationships with menstrual pain outcomes. Current research is insufficient to make definitive clinical recommendations regarding optimum dose parameters for treating primary dysmenorrhoea.
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Dysmenorrhoea can be described as painful uterine cramps of menstrual origin.1 Primary dysmenorrhoea is menstrual pain in the absence of any organic pathology and is the most common form of period pain in young women,2 as well as the most frequently under-reported cause of period pain.3 Prevalence rates among reproductive aged women range from 16.8% to 81%.4 While standard biomedical treatments, usually non-steroidal anti-inflammatory drugs (NSAIDs) or the combined oral contraceptive pill (COCP), are commonly used and effective for many women,5 ,6 approximately 25% have pain that is refractory to one or more of these standard treatments.7
Acupuncture has become a popular therapy for treating menstrual disorders in recent years.8 A recent Cochrane review examined the effectiveness and safety of acupuncture for primary dysmenorrhoea and reported unclear results for the reduction of menstrual pain, mostly due to an inability to combine the data due to evidence of excessive skew.9 While the review incorporated criteria for assessing the methodological quality of trials, the existence of a possible dose-response phenomenon has not been investigated.
There is both theoretical and empirical support for the hypothesis that alterations in acupuncture dose have an impact on therapeutic outcomes. Women with primary dysmenorrhoea show reduced uterine blood flow,10 impedance to which can be improved with both manual acupuncture (MA)11 and electroacupuncture (EA)12 in non-pregnant women. Menstrual pain is strongly correlated with reductions in uterine blood flow.13 Stener-Victorin et al12 found a dose-response relationship between the number of EA treatments and increases in uterine blood flow, which may also be relevant for menstrual pain. There is also evidence of a dose-response relationship when acupuncture and related techniques are used for non-gynaecological pain conditions14 or subfertility.15 Other complex interventions such as psychotherapy16 also show a clear dose-response relationship. While theoretically sound, the current evidence for the existence of a dose-response phenomenon when treating primary dysmenorrhoea is unclear.
We previously used the Delphi process to identify treatment components that are considered to contribute to the ‘dose’ of acupuncture, including: the number of needles; type of stimulation; retention time; and number of treatments.17 White and colleagues,18 in their review on acupuncture ‘dosage’, found that attempts to discuss whether or not the dose of acupuncture had been adequate included the following components: the number of treatment sessions; the number of acupuncture needles; the length of the session(s); and mode of stimulation. Hao et al19 found that the components of acupuncture dose that affected the outcomes for tension-type headache were mode of stimulation, needle retention time and frequency of treatment.
This review explores the relationship between the components of acupuncture dose and menstrual pain in women with primary dysmenorrhoea. Wherever possible, the effect of varying dose components were compared within the same study, otherwise potential relationships were investigated across studies. Due to the small number of studies examining each component and the issues with meta-analysis encountered in our most recent systematic review,9 our objective from the outset was to synthesise and report outcomes using a narrative style.
Based on the recommendations of Smith et al17 and White et al,18 as well as the findings of Hao et al,19 we extracted, grouped and reported four different components of acupuncture dose and examined their relationship with menstrual pain intensity: (1) neurophysiological dose reflected by the number of needles, retention time and mode of stimulation (including de qi, and intensity and frequency of EA); (2) cumulative dose comprising the total number and frequency of treatments delivered during a treatment course; (3) choice of needle location based on the underlying theoretical framework (often reported in studies as point location); and (4) timing of treatments. Due to the cyclical nature of menstruation, many studies timed their treatments in relation to the start of menses. Therefore, we also examined for a possible temporal relationship between acupuncture treatment timing and menstrual pain reduction. The two authors extracted dose components and evaluated blinding independently. Any disagreements were resolved by discussion.
A modified version of the Cochrane search strategy was used. Articles that used acupressure, non-penetrating acupuncture, non-standard acupuncture using microsystems, acupuncture point injections, transcutaneous electrical nerve stimulation (TENS), herbal medicine or moxibustion alone were not included. Only randomised controlled trials (RCTs) were included; quasi-randomised or non-randomised trials were excluded. Databases searched included Medline, PsychINFO, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, the Cochrane Library menstrual disorders subfertility group, Proquest and Web of Knowledge. All databases were searched from inception until September 2015 using the keywords ‘acupuncture’ and ‘dysmenorrhoea’. Figure 1 outlines the search and selection process. Online appendix A and supplementary material contains detailed search strategies. Papers that either had English full text or an English translation was available were included.
Inclusion/exclusion criteria and assessment of methodological quality
To be included, studies had to compare different acupuncture dose characteristics. Any study that did not have at least two verum acupuncture groups was excluded. Studies recruiting participants with a diagnosis of primary dysmenorrhoea or mixed primary and secondary dysmenorrhoea were included; studies of secondary dysmenorrhoea only were excluded. Participants needed to be aged ≥16 years. All included trials were assessed for risk of bias according to the Cochrane criteria.
The primary outcome was menstrual pain, measured by visual analogue scale (VAS), numerical rating scale (NRS), Cox menstrual symptom scale (CMSS) or the McGill pain questionnaire. Definitions of ‘effectiveness rates’ reported by Chinese language studies differed for each study, and did not follow set criteria (see online supplementary table S1 for details of effectiveness criteria for each study).
Follow-up outcome data related to menstrual pain was categorised as immediate (<48 hours after last treatment), short term (2 days to 3 months after the last treatment) and long term (4–12 months after the last treatment). The CMSS20 records both pain and secondary symptoms, combining the two domains. Therefore, when VAS and CMSS were both present, VAS was used preferentially as this only relates to pain.
A total of 389 articles were returned, 280 studies were identified as duplicates, and 109 articles were screened for eligibility. Two trials were excluded as they were subsets of the dataset reported in Liu et al.21 In total, 11 RCTs provided data that could be used to explore the relationship between dose and pain outcomes (figure 1).
Effect of acupuncture dose on menstrual pain
Six studies11 ,21–25 investigated the effect of needle location, three studies26–28 explored the effect of changing mode of stimulation while two studies29 ,30 investigated the effect of treatment timing. No studies were found that examined the effect of needle retention time, frequency of treatment or total number of treatments on pain outcomes. Dose components for all included studies are outlined in table 1.
Table 2 describes the included studies that examined the impact of changing the number of needles, the retention time or the mode of stimulation. All 11 included studies reported elicitation of de qi sensation. One study26 examined the effect of changing de qi sensation with MA. Acupuncture with strong manual stimulation, as indicated by increased de qi sensation, had a greater immediate effect on pain than acupuncture without manual stimulation (minimal de qi sensation) for both pain intensity and pain duration. No short-term or long-term follow-up was included. One study27 examined two styles of MA, one using the ‘Qinglong Baiwei’ method at LI4 and LR3 compared with standard MA at CV3/CV4 or BL32/SP6. The ‘Qinglong Baiwei’ method involves inserting the needle obliquely, achieving de qi then moving the needle slowly from side to side (as if it were a rudder in a boat) nine times. Immediate pain relief was greatest in the group receiving the ‘Qinglong Baiwei’ method while short-term pain relief was similar between both acupuncture groups. However, this study varied both needle location and type of stimulation and therefore does not provide useful information about the relative contribution of each component. One study28 examined MA versus EA using ‘superficial’ in-dwelling acupuncture and found that EA resulted in a more rapid onset of pain reduction in the 30 min after treatment (p<0.05); however, there was no significant difference between the overall ‘clinical effectiveness rate’ at the conclusion of the treatment course (91.23 vs 94.74, p>0.05) between MA and EA. No studies examined the effect of changing needle retention time.
Table 3 describes the included studies that examined the effect of changing needle location. Four studies21–24 examined the effect of EA at SP6, GB39 or an unrelated acupuncture point. All studies concluded that EA had a significant and immediate effect on pain. Studies were inconsistent regarding the importance of point specificity in reducing pain. Immediate pain relief was similar for SP6 and GB39 but superior to an unrelated acupuncture point,24 with one study showing no difference between points22 and two studies21 ,23 showing SP6 to be superior. Short-term pain relief did not differ between groups.24
One study11 examined the effect of MA at SP6 vs GB39 and found that needling at SP6 resulted in greater immediate pain reduction compared to GB39. One small study25 examined the effect of MA at traditional acupuncture points versus ‘non-channel’ points. Examination of responder rates showed that more women in the traditional acupuncture point group achieved ≥50% improvement in pain (90.9%) compared with the non-channel group (36.4%) for long-term pain (p<0.05). However, no significant difference between groups was found for the pain scores themselves, either short- or long-term.
Table 4 outlines the included studies that examined the effect of changing treatment timing in relation to the start of menses. One large study30 varied both the number of needles used and treatment timing. Immediate pain relief, as measured by a VAS, was greatest in the two groups that had treatment during menses regardless of the number of points used (p<0.01); however, the raw numerical data were not published. Treatment before menses at multiple points including SP6, SP8, Bl32 and Shiqizhui produced a greater short-term reduction in pain than treatment at the single point Shiqizhui. By contrast, when treating during menses the single point was superior to multiple points. Overall treatment before menses at multiple acupuncture points produced the greatest short-term reduction in CMSS scores. One study29 examined the effect of treatment timing only. MA given 3–7 days before menses was significantly better at reducing short-term pain intensity and short-term pain duration than acupuncture starting from the first day of menses.
No studies undertook direct comparisons between the number of treatments.
Trials with either single, weekly or monthly25 ,28 treatment did not show a trend towards reduced pain compared to those with daily treatment21 ,23 ,24 ,26 ,27 ,29 ,30 for immediate, short-term or long-term outcomes. Furthermore, no studies undertook direct comparisons of the frequency of treatment.
Overall risk of bias was moderate to high in all of the included studies (see online supplementary figure S1). Randomisation was performed adequately in all but one study, although allocation concealment was poor in almost two thirds of the included studies. Lack of blinding caused a high risk of bias in over half of the included trials. There was a low risk of bias for incomplete outcome data, while selective reporting and other sources of potential bias were unclear in most studies. Online supplementary figure S2 outlines the risk of bias for each of the included studies. The process of exclusion of secondary dysmenorrhoea, or attempts to distinguish between primary and secondary dysmenorrhoea, were not clearly reported in most trials. Therefore, it is possible that these trials included some women with secondary dysmenorrhoea.
Supplementary figure 1
Supplementary figure 2
Overall, few studies included in this review undertook direct comparisons of acupuncture dose, meaning that for most components there was no clear relationship between dose and pain outcomes. Overall, the included studies demonstrated a high degree of variation with respect to the characteristics of the intervention and treatment outcomes, especially in terms of when pain scores were measured. Those studies that included a no-treatment or wait-list control group showed that the acupuncture intervention appeared to provide an immediate analgesic effect,22–24 ,29 ,30 irrespective of the dose delivered.
The magnitude of the effect of changing mode of stimulation, on the continuum from no stimulation through manual stimulation to EA, was unclear due to the small number of trials. A recent white paper by Langevin and colleagues highlighted the inherent difficulties in comparing MA and EA, as all of the included trials that used EA obtained de qi via manual stimulation before the addition of EA; therefore, the included studies may be more accurately interpreted as comparing MA versus MA+EA rather than MA versus EA.31 The importance of de qi in treating menstrual pain is still unclear; while Xiong26 found an effect on immediate menstrual pain, a more recent analysis on the importance of de qi in the treatment of primary dysmenorrhoea casts doubt on this finding.32 When considering the number of needles used, there were no obvious dose-response relationship across studies; interestingly, however, one study suggested that treatment using a single needle during menses may give better results, whereas multiple needles may be superior before menses.30 This may reflect an increased sensitivity to acupuncture during menstruation itself.
Needle location differed significantly across trials; however, SP6 was common to all but one trial.25 The clinical usage of SP6 in trials of traditional Chinese acupuncture is most likely due to its historical usage in dysmenorrhoea,33 which has been reinforced by experiments in animal models that have provided support for the physiological effects of acupuncture at SP6.34 The trial that did not use SP625 found no differences in pain scores between groups; however, the very small sample size of this trial means that it is difficult to draw any conclusions about the relative importance of needle location.
All trials undertaken in China appeared to consider timing in relation to menses, with treatment starting either less than a week before onset of menses, or at the beginning of menses itself. Justification was not given for this choice but may reflect possible differences in the way acupuncture treatment is delivered in China compared to the rest of the world.9 Two studies29 ,30 found that treatment administered before menses provided greater short-term pain relief than treatment that started on the first day of menses; however, treatment during menses may provide more significant immediate pain relief.30 Given the more favourable short-term clinical outcomes when treatment was given before menses, rather than at the onset of menses, it is possible that those trials that delivered acupuncture only during menses may have underestimated the treatment effect;21–24 ,28 however, this relationship needs to be investigated further.
Examining the relationship between dose components and menstrual outcomes has also provided some insight into the possible mechanisms underlying acupuncture treatment of primary dysmenorrhoea. Mayor35 argues that EA implicitly provides a greater dose of stimulation compared to MA alone, based on greater activation of endogenous opioid mechanisms (EOM). The single trial comparing MA with EA showed a more rapid onset of pain relief in the EA group.28 Both Zhi28 and Liu et al24 reported the time course of pain reduction following EA and found pain relief peaked within 30 min and, in the case of Liu et al, began to decline by 60 min post-treatment, which follows the typical time course of acupuncture-induced endogenous opioid release.36 Due to the involvement of EOM, the additional pain reduction provided by electrical stimulation is likely to only be transient, with other mechanisms significantly contributing to the observed reduction in overall menstrual pain including changes in uterine blood flow11 and reduced prostaglandin levels.28 ,37 Supporting the influence of multiple mechanisms in addition to EOM, Zhi28 found that there was no significant effect of changing the mode of stimulation when looking at the overall clinical therapeutic effect. The largest included trial suggested that SP6 offers a greater immediate pain reduction when compared to GB39.21 This difference is likely due to the fact that SP6 is segmental to the uterus while GB39 is not.38 This segmental activation at the level of sacral spinal nerve 2 (S2) may lead to reflex sympathetic inhibition of the uterus12 resulting in increased uterine blood flow.11 Additional support for immediate pain reduction being mostly secondary to EOM comes courtesy of Ma et al,30 who showed that a greater number of needles causes a more rapid and sustained reduction in pain compared to a single needle when treatment is delivered during painful menstruation. There may also be additional mechanisms by which acupuncture-like treatments can relieve primary dysmenorrhoea; for example, by inactivation of myofascial trigger points on the abdomen using wet needling.39
Overall, trial quality was low, which provides several caveats to causally linking the dosing used in these trials (either high-frequency, daily treatment or EA) directly to improved menstrual pain outcomes; there may be a reporting bias in the studies included in this review and some studies have used non-validated outcome measures such as effectiveness scores or CMSS scores, which incorporate multiple domains rather than just pain reduction.
The strengths of this review include its use of all publically available databases plus those provided by the Cochrane Menstrual Disorders and Subfertility Review Group. Data were extracted and checked independently by the two reviewers with any disagreements resolved by discussion. Dose components were assessed based on previously published guidelines. The primary weakness of this review is the limitation on language; only those trials published with full text in English, or where an English translation had been undertaken during a Cochrane review, were included. This excludes a large body of Chinese language only research. Trials that did not include more than one acupuncture group were excluded from this review. Although this was commensurate with our primary aim of comparing dose between active treatment groups, consequently some high quality studies may have been excluded. Finally, due to skewing of the data, pooled analysis was not possible.
The relationship between acupuncture dose and menstrual pain was unclear, primarily due to the individual variation in the timing of outcome measures that prevented direct comparison. Findings from this review demonstrate that EA may provide more benefit than MA in immediate pain reduction during menses; however, treatment was only delivered on the first day of menses and used an uncommon style of superficial acupuncture. Treatment in the week before menses appears to provide greater benefit than treatment delivered during menses. Overall trial quality was low. Future RCTs should be designed to explore directly the potential effects of variable acupuncture dose on menstrual pain using validated outcome measures.
We would like to thank Helen Nagels from the Cochrane Menstrual Disorders and Subfertility Review Group, Dr Xiaoshu Zhu, Professor Cindy Farquhar, Professor Hannah Dahlen, Brendon Hooker and Carol Yang.
Contributors MA conceptualised the review, performed the searches, extracted the data and wrote the manuscript. CAS contributed to the conceptualisation, extracted the data and commented on the manuscript.
Funding This review consists of material generated as part of MA's PhD thesis. The Australian Postgraduate Association (APA) provided funding for this thesis.
Competing interests MA has recently finished his PhD on acupuncture for primary dysmenorrhoea. CAS has published an RCT on acupuncture for primary dysmenorrhea which was not included in this review.
Provenance and peer review Not commissioned; externally peer reviewed.
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