Effects of acupoint-stimulation for the treatment of primary dysmenorrhoea compared with NSAIDs

12 Pages·2017·1.81 MB·English

by  Yang Xu

Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436
DOI10.1186/s12906-017-1924-8
RESEARCH ARTICLE Open Access
Effects of acupoint-stimulation for the
treatment of primary dysmenorrhoea
compared with NSAIDs: a systematic review
and meta-analysis of 19 RCTs
Yang Xu1,2†, Wenli Zhao1,3†, Te Li4, Huaien Bu5, Zhimei Zhao6, Ye Zhao7,8* and Shilin Song9*
Abstract
Background: Primarydysmenorrhoea(PD),definedaspainfulmensesinwomenwithnormalpelvicanatomy,isoneof
themostcommongynaecologicalsyndromes.Acupoint-stimulationcouldpotentiallybeaneffectiveinterventionforPD.
Ouraimwastodeterminetheeffectivenessofacupoint-stimulationcomparedwithNon-SteroidalAnti-Inflammatory
Drugs(NASIDs)inthetreatmentofPD.
Methods:SixdatabasesweresearchedtoDecember2014.Sixteenstudiesinvolving1679PDpatientswereincluded.We
includedrandomizedcontrolledtrialsthatcomparedacupoint-stimulationwithNASIDsforthetreatmentofPD.Themain
outcomesassessedwereclinicaleffectivenessrate,symptomscore,visualanaloguescore,variationinperipheralblood
prostaglandinF2α(PGF2α)andsideeffects.AllanalyseswereperformedusingComprehensiveMeta-Analysisstatistical
software.
Results:(1)Thetotalefficacywasbetterthancontrolgroup:oddsratio=5.57;95%confidenceinterval(95%CI)=3.96,7.
83;P<0.00001;(2)TheeffectofinterventionwaspositiveinrelievingtheseverityofPDsymptoms:meandifference
(MD)=2.99;95%CI=2.49,3.49;P<0.00001;(3)Nostatisticaldifferenceexistedbetweentwogroupsintermsofa
reductionintheVAS:MD=1.24;95%CI=−3.37,5.85;P=0.60;(4)Theeffectofinterventiononthevariationinperipheral
bloodPGF2αbetweentwogroupswaspositive:MD=7.55;95%CI=4.29,10.82;P<0.00001;(5)Thesideeffectsofcontrol
groupswasmorethantheacupoint-stimulationgroup:OR=0.03;95%CI=0.00,0.22;P=0.0005.
Conclusions:Accordingtothisarticle,acupoint-stimulationcanrelievepaineffectivelyinthetreatmentofPDandoffers
advantagesinincreasingtheoveralleffectiveness.
Keywords:Acupoint-stimulation,Primarydysmenorrhoea,Meta-analysis,Systematicreview,Non-steroidalanti-
inflammatorydrugs
Background inCanada[2], 48.4% inMexico[3], and79.9%inIran[4].
Dysmenorrhea is the most common gynecologic com- Over 50% of females of reproductive age have painful
plaint among adolescent and young adult females. The menstruation; among them, 10% have severe dysmenor-
prevalence of dysmenorrhoea appears to differ across the rhoea, whereby their monthly lives’ quality is impaired
world,ranging from80%inWesternAustralia[1],to60% from1to3daysdifferently[5].Itstartssomehoursbefore
menstruation and continues for up to 48–72 h, and takes
the form of pains and cramps in the lower abdomen
*Correspondence:[email protected];[email protected]
†Equalcontributors radiating towards the inner side of the thighs [6]. Half
7DepartmentofChemicalEngineering,UniversityofFlorida,1006Center ofsuchcasesexperiencesystemicsymptoms,suchasnau-
Drive,Gainesville,FL32611,USA sea, vomiting, diarrhoea, fatigue, irritability and dizziness
9LaboratoryofAnatomy,SchoolofIntegrativeMedicine,TianjinUniversityof
[7, 8], which reduce the quality of life. The patients with
TraditionalChineseMedicine,No.88YuQuanRoad,NankaiDistrict,Tianjin
300193,China mild-to-moderate pain can manage their pain without
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InternationalLicense(http://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricteduse,distribution,and
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Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page2of12
drugs or with a small amount of non-prescription drugs. Methods
However, approximately 15% of all women experience se- Searchstrategy
vere dysmenorrhoea to a level that affects work or study; We searched six electronic databases that included
suchwomenneeddrugstorelievetheirpain[9].Dysmen- PubMed, the Cochrane Library, Embase, the Chinese
orrheainadolescentsandyoungadultsisusuallyprimary, Academic Journals Full-text Database, the Chinese
and is defined as painful menses in women with normal Science and Technology Journal Full-text Database
pelvicanatomy[10].In~10% offemaleswithseveredys- (CNKI), Wanfang Data, and the Chinese Biomedical
menorrhea symptoms, pelvic abnormalities such as endo- Literature Database (VIP). The index terms were the
metriosis or uterine anomalies may be found (secondary following: dysmenorrhoea, menorrhagia, painful men-
dysmenorrhea) [11]. This article mainly discusses primary struation, menstrual, pain, painful menstruation, men-
dysmenorrhoea(PD). strual pain, menstrual pains, acupuncture, moxibustion,
In recent years, there are more and more researches auricular point, ear acupoint (administering persistent/
aboutthepathogenesisofPD.Inadditiontofactorsrelating temporary pressure with Cowherb seed/finger force to
tothebody’snerve,geneticandimmunesystems,andpsy- stimulate pressure points), electroacupuncture, acusec-
chological/social factors, the pathogenesis is generally con- tor, acupoint application, randomized controlled trials,
sidered to be mainly related to two factors: (1) abnormal controlled clinical trials, and random. The above terms
uterine contraction, and (2) endocrine and metabolic fac- in Chinese were adapted and searched in Chinese data-
tors. The state of uterine ischemia and hypoxia causes the bases. The studies were published between the first year
uterine muscle to contract, increasing intrauterine tension, they were available and December 2014, which of the
and so leading to abdominal pain. Patients with abnormal languageisChinese andEnglish.
uterinecontractionsandthesubjectivefeelingofabdominal
colichavebeenconsistentlyreportedovertime.Manytypes Selectioncriteriaandexclusioncriteria
of molecular endocrine factors play an important role in Selectioncriteria
the pathogenesis of PD, such asprostaglandins (PGs), oxy-
tocin (OT) and vasopressin (VP), β-EPs, nitric oxide (NO), (cid:1) ResearchType
noradrenaline (NE), endothelins, and magnesium and (cid:1) Research Subjects
calcium ions. In particular, prostaglandin F2α (PGF2α), (cid:1) Interventions
cyclooxygenase (COX) metabolite of arachidonic acid, (cid:1) Outcomes(Clinical effectivenessrate, Symptom
causes potent vasoconstriction and myometrial contrac- score,Visual analoguescore,Peripheral blood
tions,leadingtouterineischemiaandpain[12]. PGF2α,Sideeffects)
Treatment for PD includes a variety of pharmaco-
logical and non-pharmacological methods. Common Researchtype
pharmacological interventions include Non-Steroidal Randomizedcontrolledtrials(RCTs).
Anti-Inflammatory Drugs (NASIDs) and oral contracep-
tives. NSAIDs are widely used as the first-line therapy Researchsubjects
for females with dysmenorrhoea [13, 14]. However, there Patients with a definite PD diagnosis: PD is defined as
are often adverse events associated with the use of painful menses in women with normal pelvic anatomy.
NSAIDs, including stomach ache, diarrhoea, nausea, and An eligible patientisdiagnosedbased onthe PD Clinical
liver or kidney damage after discontinuing medication GuidelineoftheSocietyofObstetriciansandGynaecolo-
[13]. Therefore, manypatientswith PD are seeking com- gistsofCanada.
plementary and alternative techniques such as acupoint-
stimulationtotreat thesymptomsofPD[15],whichem- Interventions
phasizes stimulating the acupoint(s) to strengthen the Intervention groups –acupoint-stimulation, including acu-
body’s endogenetic regulated function, so as to prevent- puncture, moxibustion, ear acupressure, electroacupunc-
ing and treating diseases by regulating the meridian ture,acupointapplication;Controlgroups–NSAIDs.
system.
Although previously publications have reported that Outcomes
acupuncture-related treatments are effective for primary (1)Clinicaleffectivenessrate
dysmenorrhea, the evidence is low convincing due to in- It was a dichotomous outcome and the overall effect-
sufficient methodological quality and small sample size. iveness of acupoint-stimulation therapy as a subjective
Given the safety of acupoint-stimulation [16], therefore, assessment, which was defined as the proportion of par-
the purpose of this systematic review and meta-analysis ticipants who got relieved pain and was based on re-
study is to determine the effectiveness of acupoint- sponse evaluation criteria used in the treatment of
stimulationintreating PD. insomnia with acupoint-stimulation. What’s more, it was
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page3of12
Fig.1PRISMA2009FlowDiagram
reported by trial participants themselves. For example, change. The total number of “cure, markedly effective,
clinical therapeutic effect criteria were categorized as effective” were used to calculate effective rate.
cure, markedly effective, effective, or ineffective. Ac- (2)Symptomscore
cording to the Guideline for Clinical Trials of New InaccordancewiththeGCTNPCM,thepatients’symp-
Patent Chinese medicines (GCTNPCM) [17] evalu- tomscoreswererecordedbeforeandaftertreatment[18].
ation standards, which define: Cured: after treatment, (3)Visualanalogue score (VAS)
the score of symptoms was;restored to 0, abdominal In the paper, we draw a 10 cm above the horizontal
pain and other symptoms disappeared and the dys- line and horizontal line of the end of 0, indicating no
menorrhea did not recurred 3 menstrual cycles after pain; on the other side of 10, said the pain; middle part
treatment; Markedly effective: after treatment, the of said varying degrees of pain. Feel the patient accord-
score of symptoms was decreased to less than 1/2 of ing to uniform mark on the horizontal line, indicating
the score before treatment, abdominal pain obviously thedegreeofpain[19].
relieved and other symptoms improved and the pa- (4)Peripheralblood PGF2α.
tient without taking analgesics could insist in work; The blood was taken from cubital vein within 24 h in
Effective: after treatment,the score of symptoms de- the last menstrual period before treatment and within
creased to 1/2–3/4 of the score before treatment, ab- 24 h in the next menstrual period after treatment for
dominal pain relieved and other symptoms improved, one course, and the plasma PGF2α levels in the two
and the patient could work after taking analgesics; In- groupsweredeterminedwithradioimmunoassay.
effective: abdominal pain and other symptoms did not (5)Sideeffects
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page4of12
hs hs hs hs hs hs hs hs hs hs hs
ollow-pVisit mont mont mont mont mont mont mont mont mont mont mont
Fu 3 3 6 3 3 3 3 3 3 3 6
Timeofinitiationofacupoint-stimulationandCourseofTreatment Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor3daysfor3menstrualcycles Thetreatmentstarted5daysbeforemenstrualonset,onceeverydayandwasgivenfor–45daysfor3menstrualcycles Thetreatmentstarted2daysbeforemenstrualonset,onceeverydayandwasgiven–for45daysfor3menstrualcycles Thetreatmentstartedduringthemenstrualperiod,onceeverydayandwasgivenfor3menstrualcycles Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor5daysfor3menstrualcycles Thetreatmentstarted7daysbeforemenstrualonset,onceeverydayandwasgivenfor7daysfor3menstrualcycles Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor6daysfor3menstrualcycles Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor5daysfor3menstrualcycles Thetreatmentstartedduringthemenstrualperiod,onceeverydayandwasgivenfor3menstrualcycles Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor6daysfor3menstrualcycles
+
Secondary N/A Uterinearterybloodflowsignals +PGFα2recurrencerate symptomscore+VAS+sideeffects symptomscore+analgesictime VAS+COX+PGFα2OT+sideeffects PGFα2 symptomscore+sideeffects symptomscore N/A N/A
y y y y y y y y y y
c c c c c c c c c c
a a a a a a a a a a
c c c c c c c c c c
Outcomes Primary Clinicaleffi Clinicaleffi Clinicaleffi Clinicaleffi Clinicaleffi N/A Clinicaleffi Clinicaleffi Clinicaleffi Clinicaleffi Clinicaleffi
p
Controlgrou Indometacin Ibuprofen Ibuprofen Ibuprofen Indometacin Fenbid Ibuprofen Indometacin Fenbid Indometacin Indometacin
e e
h Intervention Interventiongroup AcupunctureatSP10SP6CV6LI4 Eyeacupunctureatthjiaolower-area;liverarea;kidneyarea;theliverarea;theheartarea;thespleenarea Eyeacupunctureatthjiaolower-area;liverarea;kidneyarea;theliverarea;theheartarea;thespleenarea AcupunctureatEX-B8SP8BL32 SuperficialneedlingatSP6 MoxibustionatCV4CV8SP6 MoxibustionatCV4SP6 SandwichedmoxibustionatCV8 ElectroacupunctureatBL32 EaracupointatTF2CO18CO10CO12
c
Sear ±2.60
ntheLiterature Age(I/C) ––1327/1125 ––1530/1530 ––1530/1529 ––1529/2028 19.60±3.20/18.93 –1335 ––1628/1827 ––1826/1925 –1930 ––1628/1524 ––1428/1327
i
d ol
entifie en/Contr
9TrialsId SampleSizInterventio 45/45 80/60 60/50 29/30 60/60 69/64 40/40 51/51 30/30 30/28 36/36
1 er
e b
h m
t u
of on e e e e mn e e e e
acteristics RandomizatiMethod Randomnumbertabl Randomnumbertabl Randomnumbertabl Randomnumbertabl SPSSRando Randomnumbertabl Registrationorder Randomnumbertabl Randomnumbertabl Randomnumbertabl
har al.
Table1C Studies ZhangLMet(2012)[22] LinQetal.(2012)[23] HuYLetal.(2012)[18] CaoYetal.(2011)[24] ZhiLXetal.(2007)[25] BoLNetal.(2013)[26] RenXLetal.(2013)[27] ZhuYetal.(2010)[28] LiJMetal.(2012)[29] WangKetal.(2005)[30]
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page5of12
hs hs hs hs hs
nt nt nt nt nt
o o o o o
A m m m A A m m
N/ 3 3 6 N/ N/ 3 3
Thetreatmentstarted2daysbeforemenstrualonset,onceeverydayandwasgivenfor4daysfor6menstrualcycles Thetreatmentstarted7daysbeforemenstrualonset,onceeverydayandwasgivenfor10daysfor3menstrualcycles Thetreatmentstarted7daysbeforemenstrualonset,onceeverydayandwasgivenfor10daysfor3menstrualcycles Thetreatmentstarted7daysbeforemenstrualonset,onceeverydayandwasgivenfor7daysfor3menstrualcycles Thetreatmentstarted7daysbeforemenstrualonset,onceeverydayandwasgivenfor9daysfor6menstrualcycles Thetreatmentwasgiventhreetimesonthe5thand2nddayspriortotheexpectedmenstruationdateandonthethirddayofmenstruationfor1month Thetreatmentstarted4daysbeforemenstrualonset,onceeverydayandwasgivenfor7daysfor3menstrualcycles Thetreatmentstartedduringthemenstrualperiod,onceeverydayandwasgivenfor3menstrualcycles Thetreatmentstarted3daysbeforemenstrualonset,onceeverydayandwasgivenfor6daysfor3menstrualcycles
+
e e e
scor scor scorGE2
m m mP
o o o+
A mpt A mpt S A A mptFα2
N/ sy N/ sy VA N/ N/ syPG
acy acy acy acy acy acy acy
effic effic effic effic effic effic effic
al al al al al al al
nic nic nic nic A nic nic nic
Cli Cli Cli Cli N/ Cli Cli Cli
m
u
di
n n o n n n
aci aci n ns aci aci aci
Indomet Fenbid Indomet Ibuprofe Naproxe Indomet Indomet Indomet
n
6 o
(Continued)h AcupointapplicationatCV4 AcupointapplicationatCV4CV3CV6 MoxibustionatCV4EX-B8 AcupunctureatCV4CV3SP10SP8LI4LI11 AcupointapplicationatCV3CV8BL32SP AcupunctureatHT7PC6LI4LI10SP6LR3ST36GB26SP15 AcupunctureatBL31BL32BL33LI3SP6SP8CV4ST36 Prickingbloodlettingattheliverarea;kidneyarea;theliverarea;theuterusarea;HT7 SandwichedmoxibustiatCV8
c
Sear ±6.12 9 ±4.51
dintheLiterature ––1628/1524 21.22±5.86/20.96 ––1728/1827 ––1330/1435 13.1±1.0/12.8±0. 19.35±4.33/20.55 ––1527/1632 22±3/22±2 per-protocolanalysis
ntifie ator
19TrialsIde 30/28 40/40 20/20 100/100 11/24 34/34 60/54 30/30 intention-to-tre
e n
h o
t nti
of e e e e e e me
acteristics Randomnumbertabl Randomnumbertabl Randomnumbertabl Randomnumbertabl Randomnumbertabl Registrationorder Registrationorder Registrationorder Randomnumbertabl uresdidn't
Table1Char YangMetal.(2009)[31] ChenLWetal.(2006)[32] LiuCetal.(2011)[33] ZhuCetal.(2011)[34] LiZLetal.(2012)[35] GurkanKetal.(2013)[19] JiangLY(2007)[36] XingQX(2011)[37] JiLetal.(2012)[38] Theaboveliterat
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page6of12
Fig.2Meta-analysisoftheClinicalEffectiveRate
To observe the vital signs before and after treatment (2)Trials conducted usingcombinations oftreatments
andwhethertherewerefainting,stomachache,diarrhoea, and manymedicalinterventions;
nausea, and liver or kidney damage during the treatment (3)Trials inwhich thedata wereinadequateand
andotheradverseeventsoccurred,andrecorded. difficulttoextract.
Dataextractionandqualityassessment
Exclusioncriteria Searches were conducted and the data extracted by two
independent researchers. Each trial identified in the
(1)Trials where itwasunclear whetherarandomized search was evaluated for design, eligibility criteria for
trialwas beingconducted; participants, and outcome measures. Any disagreement
Fig.3Meta-analysisoftheSymptomScore
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page7of12
Fig.4Meta-analysisoftheVAS
between researchers with regard to the eligibility of a The research team evaluated homogeneity among the
trial was resolved by consulting a third researcher. We trials via I2. If I2 was ≥50%, the trials were considered to
created a form for data extraction which included: (1) be heterogeneous, and a random-effect model based on
basic information about each trial, including the topic, a Mantel-Haenszel (MH) or inverse variance (IV) statis-
first author, dateline and journal; (2) basic information tical approach was selected. If I2 was <50%, the studies
about the patients, including the number of cases in were considered to be homogeneous, and a fixed-effects
each group and the mean age; (3) the study design and model based on an MH or IV statistical approach was
intervention; and(4)theoutcomes. used. Pooled summary statistics of the differences in the
The quality of the trials included in this study was ratio or mean of the individual studies were developed.
assessed by other two researchers according to the Pooled differences in ratios or means, and two-sided P-
Cochrane HandbookforSystematicReviews ofInterven- values were calculated and used as criteria for determin-
tions,Version 5.1.0. ing the level of statistical significance. P < 0.05 was con-
sidered to indicate statistical significance. Moreover, a
Statisticalanalyses sensitivity analysis was conducted based on the leave-
All analyses were performed using Comprehensive Meta- one-outcross-validation procedure[21].
Analysis statistical software, RevMan 5.1.0 (Cochrane
Collaboration, Copenhagen, Denmark). Continuous out- Results
come variables were analyzed using a standardized meas- Studyselection
ure;dichotomousvariableswerecomparedandtheresults A flow chart of the included/excluded studies is shown
presentedasoddsratios/riskratios(OR/RR). in Fig. 1. Database searches yielded 70 studies from
Toobtainastandarddeviationofthechangefrombase- PubMed, 28fromtheCochraneCentralRegisterofClin-
linefortheexperimentalintervention,use(R =0.5)[20]: ical Trials, 215 from Embase, 552 from CNKI, 328 from
1
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi Wanfang Data, 279 from VIP, and 479 from CBM. After
SDðCÞ¼ SDðBÞ2þSDðFÞ2−ð2(cid:3)R1(cid:3)SDðBÞ(cid:3)SD(cid:3)ðFÞÞ removal of duplicate records, 849 records remained. Fol-
lowing the first review based on the title, 149 records
SD(B) represents the standard deviation before inter- were remained, and the abstracts were reviewed based on
vention; SD(F) represents the standard deviation after thepre-definedeligibilitycriteria.Atotalof82recordswere
intervention. selectedforfulltextreviewanddataprocessing.Duringthis
Fig.5Meta-analysisofthePeripheralBloodPGF2α
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page8of12
Fig.6Meta-analysisoftheSideEffects
phase,63paperswereexcluded,so19studieswereincluded visualanaloguescore
inthefinalmeta-analysis,comprising1679participants. Three trials reported the VAS; analysis of pooled data
using a random-effect model showed that I2 = 98%, indi-
Characteristicsoftheincludedstudies cating heterogeneity. So, the trial by Cao (2011) was ex-
Table 1 shows the main characteristics of the 19 RCTs cluded from analysis, then analysis of the pooled data
[18,19,22–38]. using a random-effect model showed that there was no
statistical difference in variation of VAS between the
Clinicaloutcomes groups receiving acupoint-stimulation and the control
Clinicaleffectivenessrate groups[MD=1.24,95%CI(−3.37,5.85),P=0.60](Fig.4).
Seventeen trials examined the effects of acupoint-
stimulation and reported the clinical effectiveness rate of
treatmentforparticipantswithPDwhousedthosetherap- PeripheralbloodPGF2α
ies versus the rate for a control group. Analysis of pooled Four trials examined the effects of acupoint-stimulation
data using a fixed-effect model showed that the effect of and reported peripheral blood PGF2α of participants
intervention on the clinical effectiveness rate was positive with PD who used those therapies versus the rate for a
[OR=5.57,95%CI(3.96,7.83),P<0.00001](Fig.2).That control group. Analysis of the pooled data using a fixed-
is to say, the clinical effectiveness rate, the acupoint- effect model showed that the effect of intervention on
stimulationgroupbeingsuperiortotheNSAIDs. the variation in peripheral blood PGF2α between the
groups receiving acupoint-stimulation and the control
Symptomscore groups was positive [MD = 7.55, 95%CI (4.29, 10.82),
Six trials reported the symptom score. Analysis of P < 0.00001] (Fig. 5). In the study, it is indicated that
pooled data using a fixed-effect model showed that the acupoint-stimulation can effectively decrease peripheral
effect of intervention on the symptom score was positive blood PGF2α level in the patient of PD, so as to inhibit
[MD = 2.99, 95%CI (2.49, 3.49), P < 0.00001] (Fig. 3). PGF2α-induced spastic contraction of uterine muscle,
The curative effect of acupoint-stimulation on PD is improve the decrease of blood flow, and relieve the
significant. symptomsofthepatientofdysmenorrhea.
Fig.7Riskofbiasgraph:reviewauthors’judgementsabouteachriskofbiasitempresentedaspercentagesacrossallincludedstudies
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page9of12
Sideeffects
Three trials reported the side effects between acupoint-
stimulation and control group. Analysis of pooled data
using a random-effect model showed that I2 = 83%, indi-
cating heterogeneity. So the trial by Bo (2013) was ex-
cluded from analysis, then analysis of the pooled data
using a fixed-effect model showed that the side effects of
control groups were more than the acupoint-stimulation
group.[OR=0.03,95%CI(0.00,0.22),P=0.0005](Fig.6).
Qualityassessment
Therisksofsevenbiasesamongthe19trialswereevalu-
ated, including random sequence generation, allocation
concealment, blinding of participants and personnel,
blinding of outcome assessment, incomplete outcome
data, selective reporting, and other biases according to
the criteria in the Cochrane Handbook for Systematic
Reviews. Fifteen of the studies described correct
randomization methods. There was only one trial with
allocation concealment and blinding of participants and
personnel and blinding of outcome assessment, and
nearly all of the trials failed to mention allocation con-
cealment, the blinding of the participants and personnel,
and the blinding of outcome assessments. The methodo-
logical qualities of the included trials are summarized in
Figs. 7and8.
Funnelplotofpublicationbias
The research team performed an analysis of all the in-
cluded studies, using a funnel plot to determine publica-
tion bias in all of the literature. The outcome from the
funnel plot analysis is summarized in Fig. 9. The out-
comesuggeststhattherewaslittle publication bias.
Discussion
Meta-analysisofclinicaleffect
In the 19 RCTs included, 17 reported a clinical effective-
ness rate and 6 reported symptom scores and 4 reported
variation in the level of PGF2α in the peripheral blood
of women with PD. The meta-analysis revealed that
acupoint-stimulation is superior to NSAIDs in the treat-
ment of PD in terms of clinical effectiveness rate and
symptom improvement and reducing the concentration
ofPGF2αinperipheralblood.
Only one RCT reported uterine artery blood flow sig-
nals. The results showed that the uterine arterial pulsa-
tion index (PI) and uterine arterial resistance index (RI)
of the dysmenorrheal patients were significantly in-
creased in the eye acupuncture group before treatment.
Moreover, most studies used a subjective, self-reported Fig.8Riskofbiassummary:reviewauthors’judgementsabouteach
index of treatment effects as the outcome measure. Be- riskofbiasitemforeachincludedstudy
cause participants self-reported without additional ob-
jective outcomes, their pain status could not be assessed
accurately [39]. Furthermore, the included studies used
Xuetal.BMCComplementaryandAlternativeMedicine (2017) 17:436 Page10of12
Fig.9TotalEffectsofInterventionGroups
different treatments for the intervention group, such as Differentconclusionsofthepublishedliterature
acupuncture, moxibustion, ear acupressure, electroacu- Some evidence indicates that acupoint-stimulation is ef-
punctureand acupoint application, which of the purpose fective in treating primary dysmenorrhea [44–49], but
istohighlight thespecificityofacupoints. that evidence was largely based on one small, random-
ized, controlled trial. However, two more recent sham
ThereasonforNSAIDsbeingadrugofpositivecontrol acupuncture randomized controlled trials failed to show
NSAIDs act by inhibiting the enzyme that catalyzes the evidence of pain reduction [50, 51]. One of the major
conversion of arachidonic acid to cyclic endoperoxides, challenges may be the subjective nature of the symp-
namely COX, which in turn inhibits the production of toms’ presentations and acupoints utilized. Although a
PGs [40, 41]. The resulting lower levels of PGs lead to few reviews [15, 21, 52, 53] of acupuncture for the treat-
less vigorous contractions of the uterus, and therefore to ment of PD are currently available, none of those re-
less discomfort. Thus, NSAIDs alleviate primary dys- views analyze the potential mechanism of acupuncture
menorrheic pain predominantly through the suppression for the treatment of PD, which is the key research con-
of endometrial PGs synthesis [42]. Although NSAIDs is tent in future. Therefore, a systematic review with a
the first-line treatment for PD, it also has shortcomings, meta-analysis is necessary so that quality evidence can
which can inhibit the synthesis of COX-1, as well as be put forward for the use (or not) of acupoint-
COX-2, finally it is easy to cause adverse reactions of stimulationforthetreatmentinindividuals withPD.
gastrointestinal and central nervous system. Vane [43]
indicated in 1994 that the effective treatment effect of Limitations and strengths
NSAIDs was due to inhibition of COX-2, however, the The limitations of this evaluation system are as follows:
adverse reactions imputed the suppression of COX-1. (1) most of the researches did not mention how the
Therefore, we consider that NSAIDs may be used as a sample size was estimated, and most sample sizes were
drug ofpositive control. small, leading to a low inspection efficiency; (2) in some
Although the results are encouraging, the conclusions of the studies there was inadequate reporting of alloca-
from the current study should be carefully considered tion concealment; implementing or not fully implement-
before being applied to clinical practice specific patients ing allocation concealment will lead to an exaggerated
especially individuals with NSADIs contraindication. curative effect; (3) the results were heterogeneous on ac-
This study aims to collect all RCTs relating to acupoint- count of their use ofsubjective indicators to evaluate the
stimulation treatment of PD and use systematic review curative effect (symptom scores,VAS), so that implemen-
to gauge the effectiveness of acupoint-stimulation in the tation of the blinding method is important, but the in-
treatment of PD in order to use this treatment more cludedstudiesdidnotdescribetheimplementationofthe
widelyinclinical practice. blindingmethod;(4)thestudywaslimitedtoChineseand