Pain Medicine 2015; 16: 2243–2255
Wiley Periodicals, Inc.
Efficacy of Ginger for Alleviating the Symptoms
of Primary Dysmenorrhea: A Systematic
Review and Meta-analysis of Randomized
Clinical Trials
James W. Daily, Ph.D.,* Xin Zhang, BS,†
Da Sol Kim, MS,† and Sunmin Park, Ph.D.†
*Dept. of R&D, Daily Manufacturing Inc., Rockwell,
North Carolina, USA; †Department of Food and
Nutrition, Obesity/Diabetes Research Center, Hoseo
University, Asan, South Korea
Reprint requests to: Sunmin Park, Department of Food
and Nutrition, Hoseo University, 165 Sechul-Ri,
BaeBang-Yup Asan-Si, ChungNam-Do, 336-795,
South Korea, Tel: 82-41-540-5345; Fax: 82-41-548-
0670; E-mail: smpark@hoseo.edu.
Conflicts of Interest: James W. Daily III is President of
Daily Manufacturing, Inc., a manufacturer of dietary
supplements, no other authors have any conflicts of
interest.
Author Contribution: S.P. designed the study and
S.P., J.W.D., S.J., and D.S.K. searched RCT papers
and reviewed the papers. S.P. and J.W.D. organized
the data and the statistical analysis and contributed to
writing of the manuscript. S.P. had primary
responsibility for final content. The final manuscript
has been read and approved by all authors.
Abstract
Objective. There has been no attempt to date to syn-
thesize the available evidence for the efficacy of ginger
for treating primary dysmenorrhea. This systematic
review evaluates the current evidence for the effective-
ness of ginger for treating primary dysmenorrhea.
Methods. Literature searches were conducted using
12 electronic databases including PubMed, EMBASE,
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Cochrane Library, Korean databases, Chinese medi-
cal databases, and Indian scientific database. Search
terms used were: “ginger” or “Zingiber officinale”
and “dysmenorrhea” and “pain.” Studies using gin-
ger as a treatment of primary dysmenorrhea were
considered for inclusion. The major outcome of pri-
mary dysmenorrhea was assessed using a pain visual
analogue score (PVAS).
Results. Initial searches yielded 29 articles. Of these
original results, seven met specific selection criteria.
Four of the RCTs compared the therapeutic efficacy
of ginger with a placebo during the first 3–4 days of
the menstrual cycle and were included in the meta
analysis. The meta-analysis of these data showed a
significant effect of ginger in reducing PVAS in sub-
jects having primary dysmenorrhea (risk ratio,
21.85; 95% CI of 22.87, 20.84, P 5 0.0003). Six RCTs
out of 7 exhibited low to moderate of risk of bias.
Conclusion. Collectively these RCTs provide sugges-
tive evidence for the effectiveness of 750–2000 mg
ginger powder during the first 3–4 days of menstrual
cycle for primary dysmenorrhea.
Key Words. Ginger; Dysmenorrhea; Pain Visual Ana-
log Scale; Randomized Clinical Trials; Systematic
Review
Introduction
Primary dysmenorrhea is one of the most prevalent
gynaecologic disorders, affecting more than half of all
women of reproductive age. Primary dysmenorrhea is
defined as pain associated with menstruation in the
absence of underlying organic disease [1]. It usually
begins 6–12 months after menarche and it accompa-
nies spasmodic cramping pain in the lower abdomen
that can disseminate into the lower back and thighs [1].
Symptoms of dysmenorrhea can be incapacitating and
women experiencing severe symptoms of dysmenorrhea
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 Daily et al.
are unable to engage in normal activity and experience
increased absence from school or work. It is estimated
that severe dysmenorrhea results in the loss of 600 mil-
lion working hours and $2 billion in lost productivity
annually [2]. The prevalence of primary dysmenorrhea
varies from 30% to 90% among different ethnicities with
various severities [3].
Although the cause of primary dysmenorrhea is not fully
understood, it seems clear that increased production of
prostaglandins derived from cyclooxygenase-2 (COX)-2
and other inflammatory mediators cause excessive con-
tractions of the uterus with consequential pain and
cramping [4,5]. Previous studies have reported that the
inhibition of COX-2 by nonspecific nonsteroidal anti-
inflammatory drugs (NSAIDs) decreases prostaglandin
synthesis, contributing to their analgesic, antipyretic and
analgesic properties and making them effective for
ameliorating the severity of menstrual pain in women
[5–7]. However, frequent use of these medications have
been reported to have a failure rate of 20–25% [8], and
have adverse effects ranging from minor symptoms
such as diarrhea, stomachache, and nausea to serious
illness such as chronic kidney disease [9,10]. Although
the majority of patients experience no ill effects from
NSAIDS, many would benefit by having an alternative
treatment for reducing pain treatment for primary dys-
menorrhea with minimal adverse effects [11]. As some
herbs have anti-inflammatory and analgesic activities,
they might be useful as alternatives to NSAIDS or for
decreasing the effective dose of NSAIDS for treating pri-
mary dysmenorrhea [12].
Ginger root (Zingiber officinal Roscoe.) is used world-
wide as a spice and seasoning as well as a traditional
medicine. Ginger contains abundant nonvolatile pungent
constituents such as various types of gingerols, sho-
gaols, zingerone, and paradol [8]. Ginger and ginger’s
components have pleiotropic pharmacological activities,
such as gastrointestinal, antioxidant, cardiovascular,
analgesic, and anti-inflammatory activities [9]. Several
studies have reported ginger to exert anti-inflammatory
effects by the inhibition of inducible cyclooxygenase
(COX)-2, NF-jB, and 5-lipoxygenase (5-LOX) [8,9].
Additionally, ginger and its constituents, especially sho-
gaols, work as agonists of transient receptor potential
cation channel subfamily V member 1 (TRPV1) that is
associated with the transmission of physical and chemi-
cal stimuli [8]. TRPV1 has been a prime target for the
development of novel pain relievers (analgesics). Both
antagonists and agonists of the receptor are used for
pain treatment. Under the prolonged exposure of its
agonists such as capsaicins and shogaols TRPV1 is
desensitized, which leads to the alleviation of pain [13].
There is growing evidence that ginger has anti-
inflammatory and analgesic efficacy in humans with
osteoarthritis, primary dysmenorrhea and other acute
pains. Terry et al. [14] conducted a systemic review of
research on ginger for the treatment of pains originating
from different conditions, using 6 RCTs including 2
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osteoarthritis trials, 1 dysmenorrhea trial and 3 acute
muscle pain trials. The authors concluded that ginger
may reduce subjective experience of pain in some con-
ditions. In addition, in a recent meta-analysis of random-
ized placebo-controlled trials ginger was reported to
have efficacy for pain relief in osteoarthritis [15]. There-
fore, ginger has scientific support to justify its history of
use for pain treatment as antiquity [16], especially in
Chinese and Asian-Indian traditional medicine [17]. Sev-
eral studies have also demonstrated that ginger may
have beneficial effects for cancer prevention [18],
pregnancy-related nausea and vomiting [19], chemo-
therapy nausea [20], nausea, and vomiting after surgery
[21] and osteoarthritis [22]. However, despite the evi-
dence supporting the use of ginger for many diseases
involving inflammation, nausea and pain, the efficacy of
ginger for treating or managing primary dysmenorrhea
has not recently been systemically reviewed. As the pre-
vious review on ginger for pain, several randomized
clinical trials of ginger supplementation have been con-
ducted in young women. The purpose of the current
review was to systemically evaluate all randomized clini-
cal trials of ginger for treating primary dysmenorrhea
and to elucidate the efficacy of ginger for alleviating the
symptoms of primary dysmenorrhea. To the best of our
knowledge this is the first systematic review and meta-
analysis of RCTs on the effectiveness of ginger for pri-
mary dysmenorrhea.
Methods
Data Sources and Selection Criteria
The following electronic databases were searched:
PubMed, EMBASE, Cochrane Library, Korean databases
such as DBpia, the Research Information Service System
(RISS), and the Korean Studies Information Service Sys-
tem (KISS), Chinese medical databases such as China
National Knowledge Infrastructure (CNKI) and the Chinese
Scientific Journals Database, the Indian Medical Journals
and the Indian Journals. Dissertations were also included.
The keywords and Medical Sub Headings (MeSH) were:
“ginger,” (Primary) “Zingiber officinale,” “dysmenorrhea,”
“pain,” “randomized,” “placebo,” “controlled trial,” and
“clinical trial.” All randomized clinical trials that studied the
effects of ginger on primary dysmenorrhea in young
women were included. Studies that investigated the
effects of complex herbal remedies that included ginger
as an ingredient were excluded.
Data Extraction, Quality and Validity Assessment
The search was conducted in the databases with
proper languages of English, Korean and Chinese with
the following key words of mesh terminology: ginger,
pain, and dysmenorrhea. Three independent reviewers
(SJ, SP, DSK) screened the papers. In the first screen-
ing the related papers were identified by the titles and
abstracts of the papers and the relevant articles were
retrieved in full text and validated for inclusion in the

Figure 1 Flowchart of the selection process of the randomized clinical trials for systematic review.
systemic review. The fourth reviewer (JWD) independ-
ently validated the selected the papers.
Eligibility Criteria for Studies for This Review
All prospective randomized clinical studies using ginger
for the treatment of dysmenorrhea in women having pri-
mary dysmenorrhea were included for this systematic
review. Exclusion criteria included in vitro studies of gin-
ger for primary dysmenorrhea, studies with only an
abstract available, nonclinical trial studies, studies in
which primary dysmenorrhea was not the primary out-
come measured, and then we eliminated the duplicates.
A flow diagram of the article selection process is shown
in Figure 1. Although no language barriers were
imposed, all studies included in this review were written
in English. Dissertations about randomized clinical stud-
ies were included.
Subjects and Intervention
This systematic review included all RCTs that investi-
gated the effect of ginger powder on the symptoms of
primary dysmenorrhea in young women. The age of
subjects varied among the studies but within the range
of 13–30 years of age. Most subjects were teenagers.
Although the exclusion criteria also varied among the
studies, most studies excluded subjects with irregular
menstrual cycles, those using hormonal medication,
birth control pills or intrauterine contraceptive devices
and having a history of pregnancy and strenuous exer-
cise. The eligibility of subjects was somewhat different
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Ginger and Primary Dysmenorrhea
among the studies, but in all of the studies, the subjects
had primary dysmenorrhea but not secondary dysme-
norrhea. Primary dysmenorrhea is defined as having
pain during at least 50% of menstrual cycles or first 3
days and pain score of 3-4 based on 10 visual analog
scales. Furthermore, each study consisted of 2 cycles.
Subjects in the experimental group were provided 750–
2,000 mg ginger powder capsules per day for the first 3
days of the menstrual cycle, whereas those in the con-
trol group received placebo capsules such as lactose
[23–26]. In three studies analgesic mediations such as
mefenamic acid [27,28] or exercise [29] were used as
positive controls. Five RCTs had a two-arm parallel
design: 4 RCTs contained ginger powder and placebo
groups [24–27], but 1 RCT included ginger powder1
exercise and exercise group [29]. Two RCTs adopted a
three-arm parallel design including ginger powder group
and two control groups: 1 RCT contained two analgesic
groups using mefenamic acid and iburopen [28] whereas
1 RCT included one placebo and one analgesic group
(zinc sulfate) [23].
Outcome Measures
Outcome measures to be included in the meta analysis
were severity and duration of pain during menstruation.
The severity of pain was assessed before and after
intervention by a visual analogue scale. The pain visual
analog scale (PVAS) is a tool widely used to measure
pain. The PVAS is a valid measure that has been used
in many studies to evaluate the severity of pain including
menstruation [30,31]. Its reliability varies from 0.76 to
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0.97 in different studies [32,33]. Subjects answered a
perception of pain intensity on a 10 cm horizontal scale:
the score 0 and 10 represents no pain and worst possi-
ble pain. Duration of pain was answered by each sub-
ject to indicate the number of hours she had
experienced pain during the first three days of the men-
strual period.
Quality Assessment of the Articles
The Cochrane tool was used to assess quality of the
RCT articles included in this systematic review by deter-
mining the risk of bias [34]. This validated tool consisted
of the following 7 categories: “Random sequence gener-
ation,” “Allocation concealment,” “Blinding of partic-
ipants,” “Incomplete outcome data,” “Selective outcome
reporting,” and “Other bias.” Each category was scored
as H, high risk of bias (ROB), U, uncertain ROB, or L,
low ROB. Three independent reviewers (DSK, SP, SJ)
performed the quality assessment and disagreement on
scores were resolved through discussion.
Data Analysis
The response rates in the ginger and placebo arms
were used for calculating the risk ratio, or relative risk
(RR) (weighted according to sample size). RR and 95%
confidence interval (CI) were calculated using the
response rates for ginger (success of pain relief) as a
basis. Standard mean differences (SMD) and 95% CI
were also calculated for a pain visual analogue scale
(AVS) using the Cochrane Collaboration’s software (Rev-
Man Version 5.0 for Windows. Copenhagen: The Nordic
Cochrane Centre). The variance of the change was cal-
culated using a correlation factor of 0.4 as suggested
by the Cochrane Collaboration. If appropriate, we then
pooled data across studies using random effects mod-
els, if excessive statistical heterogeneity did not exist,
the tau2 was pooled using a random effects model
because of clinical heterogeneity between each study
such as age, dose of ginger and treatment duration.
The meta-analysis included data from parallel-group
design studies. The duration of treatment, the first 3
days of the menstrual cycle, was equivalent in all groups
and the dosage was also quite similar at 750–2000 mg/
day. However, the control group was different among
groups and the control group was divided into placebo,
analgesic (mefenamic acid, ibuprofen or zinc sulfate)
and exercise.
Six studies contained two cycles and one study [24]
consisted of 1 cycle. Five studies contained the same
methods for each cycle. However, the Kashefi et al.
study [23] used different methods: the first cycle was
the same as the rest of the protocol but the second
cycle began providing ginger or placebo from 2 days
prior to the menstruation and lasting for 5 days. Both
cycles of all studies except the Jenabi study [24] were
used for the meta analysis. As the data used for the
meta-analysis were a continuous variable of the severity
of the pain, as PVIS, and the duration of the pain, mean
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differences and standard deviations were used for the
meta-analysis. Two studies gave the percentage of sub-
jects who improved due to the treatments [27,28], and
one study did not provide standard deviations of PVIS
scores [25]. Thus, four studies [23,24,26,29] were
included in the meta analysis.
Heterogeneity of the included studies was tested using
the Higgins I2 test and meaningful heterogeneity was
determined by 50% of I2 value. When I2 value was
greater than 50, a random-effect model was used for
the meta-analysis. Funnel plots were used to detect
reporting biases for this systematic review as the num-
ber of studies induced was less than 10.
Subgroup Analysis
Each study had two cycles and each cycle was consid-
ered as an individual study. In addition, the studies con-
tained different control treatments: four studies had a
placebo control [23–26], two studies had mefenamic
acid [27,28]; and one study had exercise [29] as positive
controls. According to control treatments, studies were
divided into two subgroups: placebo studies and anal-
gesic studies. The study containing exercise as the con-
trol group was considered more like an analgesic group,
but because the two studies having an analgesic control
groups did not provide means and standard deviations,
the exercise group in the Gupta study [29] was consid-
ered a placebo control.
Results
Summary of Included Studies
In the initial electronic searches a total of 29 studies
were found and 7 duplicates were removed. After 12
studies (7 in vitro studies, 2 that were not clinical trials,
2 that did not have primary dysmenorrhea as an out-
come—mixed cases of primary and secondary dysme-
norrhea) were excluded, 10 studies remained. Finally, 7
RCTs met the inclusion criteria after removing 3 non-
RCT studies (Figure 1). The 7 RCTs were used for the
systematic review [23–29]. The main data from included
RCTs were summarized in Table 1. Surprisingly, 6 RCTs
were conducted in Iran [23,24,26–29] and 1 RCT was
from India, although ginger is commonly consumed
worldwide [25]. Five RCTs had a two-arm parallel design
(ginger powder and placebo groups) [23–26,29] and 2
RCT adopted a three-arm parallel design including gin-
ger powder [27,28]. In three-arm parallel studies, Ozgoli
et al. included two analgesic groups such as mefenamic
acid and iburopen as the control groups without a pla-
cebo group [28] and Kashefi et al. contained one pla-
cebo and one analgesic groups (zinc sulfate) [27].
Risk of Bias
The risk of bias assessment for the included RCTs is
presented in Table 2. Among 7 RCTs, 2 RCTs were
classified as high quality [24,26], 4 RCTs had a
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Table 1 Summary of randomized placebo-controlled clinical trials of ginger powder treatment of primary dysmenorrhea

First No. of Experimental Control

author Subjects; Intervention Intervention
year Study Age of (Dose, Duration, (Dose, Duration, Main Experiment Control Effect Author’s Adverse

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Ref. no. Design Subjects Included Excluded Source) Source) Outcome Results Results Size Conclusions effect

Shirvani RCT 22; Ginger (n 5 11), Irregular men- Ginger powder: Mefenamic acid Dysmenor- First cycle First cycle First cycle Ginger is as None
et al.; 2 Parallel 18 and over; Placebo (n 5 11) strual cycles, 250 mg/capsule; 250 mg/capsule rhea pain; 1.39 6 0.63 1.60 6 0.80 P > 0.05 effective as
2015 arms (Ginger mean: Primary dysmenor- History of regular Every 6 h until Every 8 h until Severity of 22 (53.9) 19 (46.3) P > 0.05 mefenamic
[27] 26.6 6 2.0 rhea for at least exercise, pain relief, for 2 pain relief, for 2 dysmenorrhea second second second cycleacid for pain
Placebo mean: 50% of menstrual Secondary dys- cycles; Zintoma cycles N (%) cycle cycle P > 0.05 relief in primary
26.6 6 2.1) cycles lasting for 1 menorrhea, (ginger powder) 1.62 6 0.71 1.49 6 P > 0.05 dysmenorrhea.
day. Use of IUD or 33 (55.0) 0.78 Ginger is an
Pain intensity OCP 27 (45.0) alternative
>40 mm based on treatment for
a 100 mm visual primary
analog scale (VAS) dysmenorrhea
Kashefi RCT 150; 15–18; Ginger (First cycle Secondary Ginger powder: Placebo Dysmenor- First cycle Placebo Placebo Ginger and Headache,
et al.; 3 Parallel (Ginger mean n 5 47, second dysmenorrhea 250 mg/capsule; Capsule; rhea pain 6.2 6 1.40 First cycle First cycle zinc sulfate heartburn
2014 arms 12.8 6 1.1; Zinc cycle n 5 45), Zinc Using hormonal 3 times/day/ Unknown dose; score second cycle 7.13 6 1.3 P< 0.001 had similar in both
[23] sulfate mean sulfate medications, birth 4 day for 3 times/day/ (1–10-Score 3.08 6 1.52 second cycle second cycle positive effects groups
13 6 1.0; (First cycle n 5 54, control pills, or 2 cycles; 4 day for VAS) 6.95 6 1.67 P < 0.001 on the
Placebo mean second cycle pain relief Ginger powder 2 cycles; Zinc sulfate Zinc improvement

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12.4 6 1.2) n 5 53), Placebo medications. Lactose First cycle First cycle of primary
(First cycle n 5 45, Zinc sulfate: 6.18 6 1.7 P < 0.001 dysmenorrhea
second cycle 220 mg second cycle second cycle pain in young
n 5 42), Capsule; 3.12 6 1.2 P < 0.001 women.
Regular menstrual 3 times/day/
cycles, Experienc- 4 day for
ing dysmenorrhea 2 cycles
during the first
three days of men-
strual bleeding,
Obtaining a score
>4
Based on 10 score
of VAS
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Table 1 Continued
First No. of Experimental Control
author Subjects; Intervention Intervention
year Study Age of (Dose, Duration, (Dose, Duration, Main Experiment Control Effect Author’s Adverse
Ref. no. Design Subjects Included Excluded Source) Source) Outcome Results Results Size Conclusions effect

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Gupta RCT 64; Ginger (n=34), Physically handi- Ginger powder Only Exercise Pain score: First cycle First cycle First cycle Combined Not
et al.; 2 Parallel 17–19; Control (n=30) capped, with exercise Few muscle 10-score 3.85 6 2.45 4.43 6 1.99 P 5 0.304 effect of ginger reported
2013 arms (Ginger mean Attained menarche. Any condition in 500 mg strengthening numerical rat- 30.29 6 24.58 41.83 6 37.37 P 5 0.145 and exercise
[29] 514.0, Have primary which exercise is 2 times/day and stretching ing scale second cycle second cycle second cycle have higher
Control dysmenorrhea contraindicated, First three days exercises as per (NRS) 2.91 6 2.45 4.13 6 2.12 P 5 0.039 efficacy than
mean Secondary cause of menstruation; literature 150-score 21.26 6 17.55 44.20 6 50.39 P 5 0.015 exercise alone.
513.3) on gynecological, Few muscle 2 time/20 min menstrual dis-
Married or preg- strengthening First three days tress ques-
nant, and stretching of menstruation tionnaire
Irregular and exercises 2 time/ (MDQ))
absent for more 20 min
than 2 months First three days
of menstruation
Jenabi; RCT 70; Ginger (n=35), Not reported Ginger powder Placebo Dysmenor- 4.81 6 1.70 7.11 6 1.12 P < 0.001 Ginger is effective None
2013 2 Parallel 13–19; Placebo (n=34) 500 mg/capsule; Capsule; rhea pain in minimizing
[24] arms Underwent general 1 time/day/3 day Not reported score the pain severity
physical examina- 1 cycle dose and source (1–10-score in primary
tions, pain score>3 Ginger was pur- VAS) dysmenorrhea.
based on the 1–10 chased at

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score of VAS pharmacy
Rahnama RCT 120; Ginger (n=59), Diagnoses of a Ginger powder Placebo 1 Severity of Protocol-1 Protocol-1 Protocol-1 Treatment of None
et al. 2 Parallel 18 and over Placebo (n=46) disease, 500 mg/capsule Capsule pain 5.12 6 2.69 6.58 6 2.02 P 5 0.015 primary
2012; arms (Ginger mean Single, menstrual History of preg- 3 times /day Total powder Duration of 14.7 6 18.36 21.36 6 25.59 P 5 0.017 dysmenorrhea
[26] 21.4 6 2.0 cycle nancy, Taking Protocol-1 3 times/day pain Protocol-2 Protocol-2 Protocol-1 in students with
Placebo mean (21–35 days) oral contracep- 2 days before the Protocol-1 (hout/based 4.61 6 2.55 6.01 6 2.65 P 5 0.029 ginger for 5 days
21.3 6 2.2) 2–6 days of flow tives, menstrual period 2 days before the on 72 hour) 10.88 6 14.54 15.57 6 14.72 P 5 0.210 had a statically
Average blood loss BMI <19 kg/m2 and continued menstrual period (1–10-score significant effect
20–60 ml, severe or >25 kg/m2 through the first and continued VAS) on relieving
primary three days through the first intensity and
dysmenorrhea Protocol-2 three days duration of pain.
First three days Protocol 2
First three days
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Table 1 Continued
First No. of Experimental Control
author Subjects; Intervention Intervention
year Study Age of (Dose, Duration, (Dose, Duration, Main Experiment Control Effect Author’s Adverse
Ref. no. Design Subjects Included Excluded Source) Source) Outcome Results Results Size Conclusions effect

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Halder; RCT 75; Ex1 (n=25), Ex 1
Irregular or infre- Placebo control Dysmenor- Ex1 1.72 Not Combination of Not
2011 2 Parallel Not reported Ex2 (n=25), quent menstrual Ginger powder group (source rhea pain 1.36 Not reported exercise and reported
fig arms age range and Control (n=25) cycle, 1 g /capsule; was not reported) score Ex2 reported oral intake of
25] average; Primary dysmenor- Using an intra- 1 times/ day; (5-score Lik- 1.04 SD-value ginger powder
rhea in majority uterine contra- First three days ert scale) Not reported were effective
(>50%) of men- of menstruation.
ceptive device or SD-value for reducing
strual cycles, dys- taking oral con-Ex 2 severity of some
menorrhea for at traceptive pill.Ginger powder of she selected
least one day of 1 g/capsule ; symptoms of
menses, reproduc- 2 times/ day; dysmenorrhea.
tive age First three days
of menstruation
Ozgoli RCT 150; Mefenamic acid Pre-existing diag- Ginger rhizome Mefenamic acid A verbal 62% 66% Not Ginger was as Not
et al. 3 Parallel 18 and over; (n 5 50), nosed disease, powder capsule multidimen- got got better reported effective reported
2009 arms (Mefenamic Ibuprofen History of gesta- 250 mg/capsule 250 mg sional better as mefenamic
[28] acid mean (n 5 50), tion or taking oral 4 times/day 4 times/day scoring acid and
21.8 6 2.3 Ginger (n 5 50) contraceptive, First three days First three days system ibuprofen in

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Ibuprofen mean second-third grade medicinal or of menstruation of menstruation relieving pain
21.3 6 2.3 of severity of dys- herbal sensitiv- Zintoma; Ponstan; in women with
Ginger mean menorrhea based ities, BMI<19 or Ibuprofen primary
21.5 6 2.6) on grades 1–4 of >26, mild 400 mg/ capsule dysmenorrhea.
self-administered dysmenorrhea 4 times /day
questionnaire First three days
of menstruation
Grufen;

Ex, Experiment group; Con, Control group.

 Daily et al.

Table 2 Risk of bias in included trials

Patient Reporting
Random and Drop-out Intention- Selective Other No.
Sequence Allocation Practitioner Assessor or to Treat Outcome Potential of
Generation Concealment Blinding Blinding Withdrawal Analysis Reporting Bias Reference

Shirvani U U U U L L L U [28]
et al.
(2014)
Kashefi U U L L L L L U [24]
et al.
(2014)
Gupta U U H H L U U U [30]
et al.
(2013)
Jenabi L U U U L L L U [25]
(2013)
Rahnama L U L U L L L U [27]
et al.
(2012)
Halder U U U U L L L U [26]
(2011)
Ozgoli U U L L L U U U [29]
et al.
(2009)

Figure 2 Forest plot of the meta-analysis for the scores of the pain visual analog scale. (A) Inclusion of both cycles of
the 4 randomized clinical studies. (B) Inclusion of the one cycle of the 4 randomized clinical studies. Each study is identi-
fied by first author and year. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

2250

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Figure 3 Forest plot of the meta-analysis for the scores of the pain visual analog scale of RCTs with a placebo
group as the control. (A) Inclusion of both cycles. (B) Inclusion of the one cycle. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
moderate quality and 1 RCT had a low quality [29]. Two
studies used a proper method for randomization of the
subjects such as coin flipping and computer generated
random numbers [24,26] but the remaining studies did
not describe how the subjects were randomized. In
addition, 3 RCTs used blinding of patients and practi-
tioners [23,26,28] but the remaining 4 RCTs did not
mention their method of blinding. The drop-out rates
were not high and all RCTs included in this review gave
the reasons for withdrawals.
Outcomes
The severity of pain from primary dysmenorrhea was
scaled by PVIS and the results were given as the scores
in 5 RCTs [23–26,29] but two RCTs reported scores as
a percent better than the baseline [27,28]. As one of the
remaining five studies did not include standard devia-
tions, four studies [23,24,26,29] were included in the
meta-analysis. The pooled results of PVAS scores from
the 4 RCT studies are provided in Figure 2A and B as a
forest plot. In the meta analysis with pooling of both
cycles of the 4 RCTs, the pain scores were significantly
lower in the ginger group (n 5 266) than the control
group (n 5 228) (Figure 2A; P 5 0.0003). In addition, the
results of the pain scores were the same when pooling
one cycle of 4 RCTs (Figure 2B; P < 0.000001). How-
ever, as the RCT of Gupta et al. [29] used an exercise
group rather than a placebo group as the control, it was
deleted from the meta analysis. The pools of the
remaining three RCT groups with the placebo group as
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Ginger and Primary Dysmenorrhea
the control were used for meta-analysis (Figure 3A and
B): the PVIS scores were significantly lower in the ginger
group (n 5 198) as compared to the placebo control
group (n 5 168) including both cycles if available
(P 5 0.0001) (Figure 3A). In studies containing only one
cycle, the consumption of ginger (n 5 139) resulted in
lower PVAS scores than that of the placebo (n 5 122)
(P 5 0.0003) (Figure 3B).
Among the RCTs, 2 RCTs [27,28] used an analgesic
treatment as the control group. Each study calculated
the percentage of the PVAS improvement from the
baseline. Both studies showed similar percentages of
improvement in the ginger and analgesic groups (Table
1). In addition, in one study [29] the exercise group was
considered as the control group. The PVAS pain score
was similar between the exercise and ginger groups in
the first cycle but it was lower in the ginger group than
the exercise group in the second cycle (P 5 0.039).
Therefore, subjects treated with ginger powder experi-
enced less pain from primary dysmenorrhea than the
placebo supplemented subjects, furthermore the pain in
the in the ginger group was less than in the exercise
group and similar to the analgesic groups.
Publication Bias
An asymmetrical funnel plot was produced by this
meta-analysis (the hollow circles in Figure 4), which indi-
cated publication bias.
2251
 Daily et al.
Figure 4 Funnel plot of the meta-analysis for the
scores of the pain visual analog scale. The hollow
circles represent the studies in the meta-analysis. [Color
figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
Adverse Events
Six RCT did not report adverse effects whereas 1 RCT
reported heartburn, headache and diarrhea as adverse
effects [23]. However, the symptoms were not limited to
the ginger group (750 mg ginger/day) and there was no
significant differences in these symptoms between
groups (P > 0.05). Thus, ginger administration resulted
in no increase in adverse effects over placebo in the 7
RCTs included in this review.
Discussion
This meta-analysis provided evidence that ginger can ameli-
orate pain associated dysmenorrhea in women. The relief
from pain was highly significant and in the studies in which
analgesics were used as a positive control, ginger powder
was equally as effective as the analgesic drug treatment. All
of the studies, both the RCT’s included in the meta-analysis
and those that were not, reported that ginger was effective
for treating dysmenorrhea pain. However, the studies were
small (22–150 subjects) and none alone provided convinc-
ing evidence for efficacy. The doses used in the studies
ranged from 750 mg to 2,000 mg of ginger powder per day
and there was no clear difference in efficacy among the dos-
ages. Therefore, it would be prudent to begin treatment with
750 mg per day, and increase the dose when needed. The
current major treatment for primary dysmenorrhea is using
NSAIDs to reduce abdominal pain by attenuating uterine
hypercontractility. However, NSAIDs are not completely
effective and have considerable adverse effects, morbidity,
and mortality associated with their use [1]. Therefore, ginger
powder might be useful as a therapeutic agent for primary
dysmenorrhea instead of or combined with NSAIDS.
Numerous studies have investigated ginger for the amel-
ioration of pain and inflammation in various diseases,
and recent reviews and studies support its efficacy for
pain relief in rheumatoid arthritis [35], osteoarthritis [36],
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burn injury [37], migraine headache when combined
with Ferverfew herb [38], acetic acid-induced pain [39],
and chronic low back pain [40]. However, even though
ginger has been shown to be effective for many types
of pain, it is not necessarily efficacious for all pain. Stud-
ies of the use of ginger for exercise induced pain have
yielded inconsistent results with some showing modest
effects [41,42] and some no effects at all [43–45] for
treating exercise-induced muscle soreness. Although
the results are inconsistent, an observation by Black
and O’Connor [45] may provide an explanation. They
observed that the lack of effect of ginger on cycling
exercise-induced pain in quadriceps muscle is consist-
ent with a lack of effect of aspirin in similar muscle pain.
They noted that the ineffectiveness of aspirin suggests
that prostaglandins may not play a major role in
exercise-induced skeletal muscle pain. As mentioned in
the Introduction, suppressing the production of prosta-
glandins by COX-2 inhibition may be one of the major
mechanisms of the analgesic and anti-inflammatory
actions of ginger [6–9]. Therefore, although ginger has
been demonstrated to have a wide range of analgesic
efficacies, studies such as this that evaluates its effec-
tiveness on specific types of pain are important.
Bioavailability of the active components of herbs and
spices is a major limitation of most botanical medicines
[46]; however ginger and its components appear to be
well absorbed. One hour after oral consumption of ginger
its major components: 6-shogaol, 10-gingerol, 6-gingerol,
and 8-gingerol are detected in the plasma in rats and
humans [47,48] and at 48–60 h 6-gingerol, and 6-shogaol
are excreted mainly into bile and some into urine [49].
It is important that the one RCT to report adverse
effects of treatments reported only mild symptoms and
with no differences between the ginger treated group
and placebo group [23]. In a recent systematic review
and meta-analysis of ginger for nausea and vomiting
during pregnancy, the authors found 1,500 mg per day
to be most effective and without any adverse effects
[48], and there were no indications of adverse effects of
higher doses. The oral consumption of ginger powder
up to 2 g/kg body weight does not exhibit any mortality
or abnormal changes in hematological parameters in
rats [50]. The currently available studies indicate that
ginger is very safe at optimally effective dosages.
To the best of our knowledge, this is the first systematic
review and meta-analysis of RCTs on the effectiveness of
ginger for primary dysmenorrhea. Even though the results
indicate that ginger is highly effective for treating dysme-
norrhea, there are important limitations to the study that
need to be considered. The number of trials and total
sample size of the primary studies are low. A standard
scoring system was used to quantify the likelihood of bias
inherent in the studies based on the description of ran-
domization, blinding and withdrawals [34]. The seven
RCTs included in the systematic review had low to moder-
ate risk of bias. Three RCTs [24,27,29] reported double-
blinding procedures but did not report details. No RCT

studies reported the concealment of treatment allocation.
Trials with inadequate blinding and inadequate allocation
concealment may lead to selection bias and are likely to
show exaggerated treatment effects. Two RCT adopted
assessor blinding [24,29]. Others failed to do so and con-
tained detection bias. These studies are also somewhat
limited by a lack of reporting the effects of ginger on the
other symptoms associated with dysmenorrhea. Moreover
the papers did not analyze the gingerol or shogaol content
of ginger powders, and none reported whether the pow-
ders were prepared in a standardized fashion. Conse-
quently we do not know how much of each key
constituent was in the capsules, making it difficult repeat the
studies using similar ginger preparations in the future. How-
ever, it is interesting that presumably different ginger prepa-
rations were effective among all of the studies. That may be
due to the varied nature of bioactive components which may
have overlapping and/or synergistic effects. Moon et al
showed that 6-shogaol can attenuate neuroinflammation
and cognitive deficits in a mouse dementia model [51]. Fur-
thermore, 10-gingerol has also been shown to have potent
anti-neuroinflammatory capacity [52] and 6-gingerol has a
wide variety of anti-inflammatory and other pharmacological
activities [53]. Therefore, highly purified ginger preparations
run the risk of removing important bioactive compounds and
as rather modest doses of pure powder appear efficacious,
use of whole powder may be prudent until more is known
about the relative contributions of the different compounds.
Conclusions
The results of our systematic review and meta-analysis pro-
vide suggestive evidence for the effectiveness of ginger in
treating primary dysmenorrhea. However, the total number
of RCTs that could be included in this analysis, the total
sample size and the average methodological quality of the
primary studies might not be sufficient to draw firm conclu-
sions. However, the strength of the study was the consis-
tency of benefit among all of the studies and a very highly
statistically significant effect of ginger for treating pain. This
research clearly demonstrates that ginger (750–2000 mg/
day during the first 3–4 days of the menstrual cycle) is a very
promising potential treatment for the pain and discomfort
associated with primary dysmenorrhea. More high quality
studies are necessary to clearly establish the efficacy of gin-
ger for the treatment of primary dysmenorrhea.
Acknowledgment
This research was supported by the Ministry of Trade, Indus-
try and Energy (MOTIE), KOREA, through the Education
Support program for Creative and Industrial Convergence.
References
1 Berkley KJ. Primary dysmenorrhea: An urgent man-
date. Pain Clin Updates 2013;21:1–8.
2 Coco AS. Primary dysmenorrhea. Am Fam Physi-
cian 1999;60:489–96.
Downloaded from https://academic.oup.com/painmedicine/article-abstract/16/12/2243/2460294
by Universiti Kebangsaan Malaysia user
on 14 March 2018
Ginger and Primary Dysmenorrhea
3 Kim T, Park H, Lee H, Chung S. Premenstrual syn-
drome and dysmenorrhea in the career women at
Bucheon City. Kor J Obstet Gynecol 2011;54:
523–8.
4 Rosenwaks Z, Seegar-Jones G. Menstrual pain: Its ori-
gin and pathogenesis. J Reprod Med 1980;25:207–12.
5 Bieglmayer C, Hofer G, Kainz C, et al. Concentra-
tions of various arachidonic acid metabolites in
menstrual fluid are associated with menstrual pain
and are influenced by hormonal contraceptives.
Gynecol Endocrinol 1995;9:307–12.
6 Marjoribanks J, Proctor M, Farquhar C, Derks RS. Non-
steroidal anti-inflammatory drugs for dysmenorrhea.
Cochrane Database Syst Rev 2010;1:CD001751.
7 Daniels SE, Torri S, Desjardins PJ. Valdecoxib for
treatment of primary dysmenorrhea, a randomized,
double-blind comparison with placebo and nap-
roxen. J Gen Intern Med 2005;20:62–7.
8 Iwasaki Y, Morita, A, Iwasawa T, et al. A nonpun-
gent component of steamed ginger–[10]-shogaol–
increases adrenaline secretion via the activation of
TRPV1. Nutr Neurosci 2006;9:169–78.
9 Dugasani S, Pichika MR, Nadarajah VD, et al. Com-
parative antioxidant and anti-inflammatory effects of
[6]-ginerol, [8]-gingerol, [10]-ginerol and [6]-shogaol.
J Ethnopharmacol 2010;127:515–20.
10 Edwards JE, Moore RA, Mcquay HJ. Rofecoxib for
dysmenorrhea: Meta-analysis using individual patient
data. BMC Womens Health 2004;4:5.
11 Zhu X, Proctor M, Bensoussan A, Smith C, Wu E.
Chinese herbal medicine for primary dysmenorrhea.
Cochrane Database Syst Rev 2007;4:CD005288.
12 Harel Z. Dysmenorrhea in adolescents and young
adults: An update on pharmacological treatments
and management strategies. Expert Opin Pharmac-
other 2012;13:2157–70.
kova
13 Vyklicky L, Nova -Tousova
 K, Benedikt J, et al.
Calcium-dependent desensitization of vanilloid
receptor TRPV1: A mechanism possibly involved in
analgesia induced by topical application of capsai-
cin. Physiol Res 2008;57:S59–68.
14 Terry R, Posadzki P, Watson LK, Ernst E. The use
of ginger (Zingiber officinale) for the treatment of
pain: A systematic review of clinical trials. Pain Med
2011;12:1808–18.
15 Bartels EM, Folmer, VN, Bliddal H, et al. Efficacy
and safety of ginger in osteoarthritis patients: A
2253
 Daily et al.
meta-analysis of randomized placebo-controlled tri-
als. Osteoarthritis Cartilage 2015;23:13–21.
16 Kizhakkayil J, Sasikumar B. Diversity, characteriza-
tion and utilization of ginger: A review. Plant Genet
Resour 2011;9:464–77.
17 Yip YB, Tam AC. An experimental study on the
effectiveness of massage with aromatic ginger and
orange essential oil for moderate-to-severe knee
pain among the elderly in Hong Kong. Complement
Ther Med 2008;16:131–8.
18 Lee SH, Cekanova M, Baek SJ. Multiple mecha-
nisms are involved in 6-gingerol-induced cell growth
arrest and apoptosis in human colorectal cancer
cells. Mol Carcinog 2008;47:197–208.
19 Pongrojpaw D, Somprasit C, Chanthasenanont A. A
randomized comparison of ginger and dimenhydri-
nate in the treatment of nausea and vomiting in
pregnancy. J Med Assoc Thai 2007;90:1703–9.
20 Ryan JL, Heckler, CE, Roscoe JA, et al. Ginger (Zin-
giber officinale) reduces acute chemotherapy-
induced nausea: A URCC CCOP study of 576
patients. Support Care Cancer 2011;20:1479–89.
21 Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S,
Leeprakobboon K, Leelasettagool C. The efficacy of
ginger for the prevention of postoperative nausea
and vomiting: A meta-analysis. Am J Obstet Gyne-
col 2006;194:95–9.
22 Haghighi M, Khalvat A, Toliat T, Jallaei S. Compar-
ing the effects of ginger (zingiber officinale) extract
and ibuprofen on patients with osteoarthritis. Arch
Iran Med 2005;8:267–71.
23 Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M,
Asili J. Comparison of the effect of ginger and zinc sul-
fate on primary dysmenorrhea: A placebo-controlled
randomized trial. Pain Manag Nurs 2014;15:826–33.
24 Jenabi E. The effect of ginger for relieving of primary
dysmenorrhoea. J Pak Med Assoc 2013;63:8–10.
25 Halder A. Effect of progressive muscle relaxation versus
intake of ginger powder on dysmenorrhoea amongst the
nursing students in Pune. Nurs J India 2012;103:152–6.
26 Rahnama P, Montazeri A, Huseini HF, Kianbakht S,
Naseri M. Effect of Zingiber officinale R. rhizomes
(ginger) on pain relief in primary dysmenorrhea: A
placebo randomized trial. BMC Complement Altern
Med 2012;12:92
27 Shirvani MA, Motahari-Tabari N, Alipour A. The
effect of mefenamic acid and ginger on pain relief in
2254
Downloaded from https://academic.oup.com/painmedicine/article-abstract/16/12/2243/2460294
by Universiti Kebangsaan Malaysia user
on 14 March 2018
primary dysmenorrhea: A randomized clinical trial.
Arch Gynecol Obstet 2015;291:1277–81.
28 Ozgoli G, Goli M, Moattar F. Comparison of effects
of ginger, mefenamic acid, and ibuprofen on pain in
women with primary dysmenorrhea. J Altern Com-
plement Med 2009;15:129–32.
29 Gupta R, Kaur S, Singh A. Comparison to assess the
effectiveness of active exercises and dietary ginger vs.
active exercises on primary dysmenorrhea among ado-
lescent girls. Nursing Midwifery Res J 2013;9:168–77.
30 Kashefi F, Ziyadlou S, Khajehei M, et al. Effect of
acupressure at the Sanyinjiao point on primary dys-
menorrhea: A randomized controlled trial. Comple-
ment Ther Clin Prac 2010;16:198–202.
31 Wong CL, Lai KY, Tse HM. Effects of SP6 acupressure
on pain and menstrual distress in young women with dys-
menorrhea. Complement Ther Clin Prac 2010;6:64–9.
32 Bijur PE, Silver W, Gallagher EJ. Reliability of the vis-
ual analog scale for measurement of acute pain.
Acad Emerg Med 2001;8:1153–7.
33 Boonstra AM, Schiphorst Preuper HR, Reneman
MF, Posthumus JB, Stewart RE. Reliability and
validity of the visual analogue scale for disability in
patients with chronic musculoskeletal pain. Int J
Rehabil Res 2008;31:165–9.
34 Higgins JP, Altman, DG, Gøtzsche PC, et al. The
Cochrane Collaboration’s tool for assessing risk of
bias in randomised trials. BMJ 2011;343:d5928
35 Al-Nahain A, Jahan R, Rahmatullah M. Zingiber offi-
cinale: A potential plant against rheumatoid arthritis.
Arthritis 2014;2014:159089
36 Akhtar N, Haqqi TM. Current nutraceuticals in the
management of osteoarthritis: A review. Ther Adv
Musculoskelet Dis 2012;4:181–207.
37 Sepahvand R, Esmaeili-Mahani S, Arzi A, Rasoulian
B, Abbasnejad M. Ginger (Zingiber officinale
Roscoe) elicits antinociceptive properties and poten-
tiates morphine-induced analgesia in the rat radiant
heat tail-flick test. J Med Food 2010;13:1397–401.
38 Cady R, Schreiber CP, Beach ME, Hart CC. Gelstat
migraine (sublingually administered feverfew and gin-
ger compound) for acute treatment of migraine
when administered during the mild pain phase. Med
Sci Monit 2005;11:165–9.
39 Young HY, Luo YL, Cheng HY, et al. Analgesic and anti-
inflammatory activities of [6]-gingerol. J Ethnopharmacol
2005;96:207–10.

40 Chrubaski JE, Roufogalis BD, Chrubasik S. Evidence
of effectiveness of herbal anti-inflammatory drugs in
the treatment of painful osteoarthritis and chronic low
back pain. Phytother Res 2007;21:675–83.
41 Mashhadi NS, Ghiasvand R, Askari G, et al. Influ-
ence of ginger and cinnamon intake on inflammation
and muscle soreness endued by exercise in Iranian
female athletes. Int J Prev Med 2013;4:S11–5.
42 Black CD, Herring MP, Hurley DJ, O’Connor PJ. Gin-
ger (Zingiber officinale) reduces muscle pain caused
by eccentric exercise. J Pain 2010;11:894–903.
43 Matsumura MD, Zavorsky GS, Smoliga JM The
effects of pre-exercise ginger supplementation on
muscle damage and delayed onset of muscle sore-
ness. Phytother Res 2015;29:887–93.
44 Black CD, O’Connor PJ. Acute effects of dietary
ginger on muscle pain induced by eccentric exer-
cise. Phyother Res 2010;24:1620–6.
45 Black CD, O’Connor PJ. Acute effects of dietary
ginger on quadriceps muscle pain during moderate-
intensity cycling exercise. Int J Sport Nutr Exerc
Metab 2008;18:653–64.
46 Opara E, Chohan M. Culinary herbs and spices:
Their pioactive properties, the contribution of pol-
yphenols and the challenges in deducing their
true heal benefits. Int J Mol Sci 2014;15:19183–
202.
Downloaded from https://academic.oup.com/painmedicine/article-abstract/16/12/2243/2460294
by Universiti Kebangsaan Malaysia user
on 14 March 2018
Ginger and Primary Dysmenorrhea
47 Chen H, Soroka DN, Hu Y, Chen X, Sang S. Char-
acterization of thiol-conjugated metabolites of ginger
components shogaols in mouse and human urine
and modulation of the glutathione levels in cancer
cells by [6]-shogaol. Mol Nutr Food Res 2013;57:
447–58.
48 Chen H, Soroka DN, Zhu Y, et al. Cysteine-conju-
gated metabolite of ginger component [6]-shogaol
serves as a carrier of [6]-shogaol in cancer cells and
in mice. Chem Res Toxicol 2013;26:976–85.
49 Viljoen E, Visser J, Koen N, Musekiwa A. A system-
atic review and meta-analysis of the effect and
safety of ginger in the treatment of pregnancy-
associated nausea and vomiting. Nutr J 2014;13:20
50 Rong X, Peng G, Suzuki T, et al. A 35-day gavage
safety assessment of ginger in rats. Regul Toxicol
Pharmacol 2009;54:118–23.
51 Moon M, Kim HG, Choi JG, et al. 6-Shogaol, an
active constituent of ginger, attenuates neuroinflam-
mation and cognitive deficits in animal models of
dementia. Biochem Biophys Res Commun 2014;
449:8–13.
52 Ho SC, Chang KS, Lin CC. Anti-neuroinflammatory
capacity of fresh ginger is attributed mainly to 10-
gingerol. Food Chem 2013;141:3153–91.
53 Wang S, Zhang C, Yang G, Yang Y. Biological
properties of 6-gingerol: A brief review. Nat Prod
Commun 2014;9:1027–1030.
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