Comparison of Effects of Ginger, Mefenamic Acid, and Ibuprofen on Pain in Women with Primary Dysmenorrhea

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THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 15, Number 2, 2009, pp. 129–132
© Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2008.0311
Comparison of Effects of Ginger, Mefenamic Acid,
and Ibuprofen on Pain in Women
with Primary Dysmenorrhea
Giti Ozgoli, M.Sc.,1 Marjan Goli, M.Sc.,2 and Fariborz Moattar, Ph.D.3
Abstract
Objectives: To compare the effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary
dysmenorrhea.
Methods: This was a double-blind comparative clinical trial conducted from September 2006 to February 2007.
Participants were 150 students (18 years old and over) with primary dysmenorrhea from the dormitories of
two medical universities who were alternately divided into three equal groups. Students in the ginger group
took 250 mg capsules of ginger rhizome powder four times a day for three days from the start of their men-
strual period. Members of the other groups received 250 mg mefenamic acid or 400 mg ibuprofen capsules, re-
spectively, on the same protocol. A verbal multidimensional scoring system was used for assessing the sever-
ity of primary dysmenorrhea. Severity of disease, pain relief, and satisfaction with the treatment were compared
between the groups after one menstruation.
Results: There were not significant differences between groups in baseline characteristics, p
0.05. At the end
of treatment, severity of dysmenorrhea decreased in all groups and no differences were found between the
groups in severity of dysmenorrhea, pain relief, or satisfaction with the treatment, p
0.05. No severe side ef-
fects occurred.
Conclusion: Ginger was as effective as mefenamic acid and ibuprofen in relieving pain in women with primary
dysmenorrhea. Further studies regarding the effects of ginger on other symptoms associated with dysmenor-
rhea and efficacy and safety of various doses and treatment durations of ginger are warranted.
Introduction
dometrium with menses, and approximately 80% of patients
can experience pain relief by taking prostaglandin inhibitors,
Dysmenorrhea is one of the most frequent gynecologic including proponics and phenamates.3 Non-steroidal anti-
disorders, affecting more than half of menstruating
inflammatory drugs (NSAIDs) are widely used as first-line
women. Most adolescents experience dysmenorrhea in the
therapy in women with primary dysmenorrhea. Evidence-
first few years after the menarche. Primary dysmenorrhea is
based data support the efficacy of ibuprofen, naproxen,
defined as pelvic pain around the time of menstruation in
mefenamic acid, and aspirin.4 These agents, however, have
the absence of an identifiable pathologic lesion, present from
side effects, of which gastrointestinal disorders such as nau-
menarche.1 It is a frequent cause of absenteeism and med-
sea, dyspepsia, and vomiting are the most common.5
ical visits, and affects personal as well as economic aspects
Some patients with primary dysmenorrhea do not respond
of life. It is estimated that severe dysmenorrhea results in the
to treatment with NSAIDs or oral contraceptives. In addi-
loss of 600 million working hours and $2 billion in lost pro-
tion, some women have contraindications to these medica-
ductivity annually.2
tions. Consequently, researchers have investigated numer-
Although the etiology of primary dysmenorrhea is not
ous alternative/complementary treatments such as herbal
completely understood, symptoms are generally associated
and dietary therapies,6 behavioral interventions,7 acupres-
with increased production of prostaglandins (PGs) in the en-
sure,8 and aromatherapy.9 Ginger, the rhizome of Zingiber
1Nursing and Midwifery School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2Nursing and Midwifery School, Islamic Azad University of Najafabad, Isfahan, Iran.
3Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
129

130
OZGOLI ET AL.
officinale, is a traditional medicine with anti-inflammatory
ceptives, medicinal or herbal sensitivities, body mass index
and anticarcinogenic properties.10 It is a botanical general
(BMI) 19 or 26, and mild dysmenorrhea (score 1).
recognized as safe (GRAS) by the United States Food and
The 150 patients were alternately allocated into three
Drug Administration (FDA)11 with no report of severe side
groups. Each group took their medication four times a day
effects or drug interactions in Germany’s Commission E
for three days from the start of their menstrual period. In the
Monograph.12 Ginger has been widely used in medicine, and
first group, patients received capsules containing 250 mg of
has been administered in Traditional Chinese Medicine for
ginger rhizome powder (Zintoma; Goldaru Co., Iran). The
more than 2500 years as an anti-inflammatory agent in mus-
second group received 250 mg mefenamic acid capsules
culoskeletal disorders.10 Two compounds in ginger, [6]-Gin-
(Ponstan; Razak Co., Iran) and the third group took 400 mg
gerol and Gingerdiones, are potent inhibitors of PGs by
ibuprofen capsules (Brufen; Roozdaru Co., Iran). The cap-
blocking cyclooxygenase.10,13 Traditional application of gin-
sules in all groups were similar in shape and package and
ger to relieve symptoms of dysmenorrhea has been noted in
were administered anonymously with coding by a midwife
several classical sources14 such as Kitab al Qanun fi Al Tibb
colleague with no knowledge of the codes. To measure com-
by Ibn Sina (The Canon of Medicine by Avicenna).15 However,
pliance we asked patients to report the number of capsules
to the best of our knowledge, there are no reports of a con-
they have took.
trolled study of the use of ginger in dysmenorrhea. The aim
Final assessment was performed after one menstrual pe-
of the present study was to compare the effects of ginger
riod by another colleague who had no information about the
with mefenamic acid and ibuprofen on pain in women with
groups. Patients and assessor were blinded to the groups. In
primary dysmenorrhea.
addition to the verbal multidimensional scoring system, a 5-
point scale was used to assess pain relief (considerably re-
Materials and Methods
lieved, relieved, unchanged, worse, considerably worse) and
patient satisfaction with the treatment was also assessed (sat-
This was a double-blind comparative clinical trial con-
isfied, not satisfied). Analysis of variance (ANOVA) and chi-
ducted from September 2006 to February 2007. Patients in-
square tests were used to identify any difference between the
cluded students (aged 18 years and over) with primary dys-
groups in baseline characteristics, severity of disease, pain re-
menorrhea selected by continuous sampling from the
lief, and satisfaction with the treatment; a p value
0.05 was
dormitories of Isfahan and Shahid Beheshti Universities of
considered significant. A sample size of 150 patients was re-
Medical Sciences. The purpose and method of the study were
quired assuming 90% power and estimation of improvement
explained and informed consent was obtained from all pa-
for mefenamic acid (80%) and for ginger (at least 50%).
tients. The ethics committee of Shahid Beheshti University
of Medical Science approved the study.
Results
At baseline, the severity of dysmenorrhea, demographic
data, and menstrual characteristics were assessed by a self-
At baseline, no significant differences were found between
administered questionnaire. Severity was assessed before
the groups regarding age, BMI, or menstruation characteris-
and after the intervention by a verbal multidimensional scor-
tics (Table 1).
ing system that has been used in previous studies9,16 with
There were no significant differences between the groups
four grades: painless menstruation
0, menstruation with
in severity of dysmenorrhea before or after treatment (Table
pain but rare use of analgesics or limitation of activities
1,
2). Also, no significant differences were found between the
menstruation with moderate pain with influence on daily ac-
three groups in relief, stability, or aggravation of symptoms.
tivities and use of analgesics with relief
2, and menstrua-
Compliance in using the capsules was the same in all three
tion with severe pain with significant limitations on daily ac-
groups.
tivities, ineffective use of analgesics, and such symptoms as
Four students in each group reported a slight increase in
headache, tenderness, nausea, vomiting, and diarrhea
3.
bleeding as a menstrual change. One student in the mefe-
Patients with moderate to severe dysmenorrhea (score 2 or
namic acid group and one in ginger group experienced de-
3) were included. Exclusion criteria were a pre-existing di-
creased bleeding, and one student in the ibuprofen group re-
agnosed disease, history of gestation or taking oral contra-
ported increased duration of menstruation.
TABLE 1. BASELINE DEMOGRAPHICS
Mefenamic acid
Ibuprofen
Ginger
(n
50)
(n
50)
(n
50)
Age (years)
21.8
2.3
21.3
2.3
21.5
2.6
Body mass index
22.2
2.2
22.3
2.2
22.2
2.3
Menarche (age in years)
12.9
1.3
13
1.5
12.9
0.9
Duration of menses (days)
6.4
1
6.2
1.2
6.6
1.1
Duration of cycles (days)
28
1.8
28.9
2.9
29.1
2
Interval of cycles (days)
22.4
2
22.4
3
22.6
2.3
Pads used
3.1
1
2.7
0.9
2.8
0.9
Pain in all cycles
Yes
42 (84%)
44 (88%)
47 (94%)
No
7 (14%)
6 (12%)
3 (6%)

GINGER IN TREATMENT OF PRIMARY DYSMENORRHEA
131
TABLE 2. SEVERITY OF DYSMENORRHEA BEFORE AND AFTER TREATMENT
Mefenamic acid
Ibuprofen
Ginger
(n
50)
(n
50)
(n
50)
At baseline
Moderate
31 (62%)
34 (68%)
36 (72%)
Severe
19 (38%)
16 (32%)
14 (28%)
After treatment
Painless
10 (20%)
13 (26%)
18 (36%)
Mild
12 (24%)
14 (28%)
13 (26%)
Moderate
19 (38%)
20 (40%)
25 (30%)
Severe
9 (18%)
3 (6%)
4 (8%)
Change in pain severity
Considerably relieved
15 (30%)
18 (36%)
18 (36%)
Relieved
18 (36%)
15 (30%)
13 (26%)
Unchanged
13 (26%)
17 (34%)
15 (30%)
Worse
3 (6%)
3 (6%)
4 (8%)
Considerably worse
1 (2%)
0
0
Rate of satisfaction
20 (40%)
22 (44%)
21 (42%)
Number of capsules used
11.2
1.4
11.1
1.9
11.5
1.5
Discussion
sion, colic, vomiting, diarrhea, spasms and other smooth
muscle disorders, colds, influenza, and rheumatism as an
Our findings showed that ginger was as effective as mefe-
anti-inflammatory agent.14 It has been shown that gingerols
namic acid and ibuprofen in relieving menstrual pain. Mefe-
in ginger have anti-inflammatory effects both in vitro and in
namic acid and ibuprofen are the drugs of choice for treat-
vivo.20,21 The anti-inflammatory property of ginger has been
ing primary dysmenorrhea,17 with up to 80% efficiency.3
attributed to the inhibition of cyclooxygenase and lipooxy-
Different theories exist regarding dysmenorrhea-inducing
genase, leading to reduction of leukotriene and prostaglan-
mechanisms, one of which is increased production of PGs in
din.22
the endometrium. PGs originate from arachidonic acid in cy-
Considering this evidence, it seems that ginger had anti-
clooxygenase and lipooxygenase pathways. Studies have
prostaglandin effects similar to those of mefenamic acid and
shown that the menstrual blood of women with dysmenor-
ibuprofen, and gingerols may be the principle active ingre-
rhea has greater amount of two PGs—PGE2 and PGF2 . In
dient for these effects. Measuring PGs in plasma or men-
women with primary dysmenorrhea, pain results from my-
strual blood throughout the treatment may help to clarify
ometrial contractions induced by PGs (mainly PGF2 ) orig-
the mechanism of action of ginger on primary dysmenor-
inating in secretory endometrium.3
rhea. Dysmenorrhea is sometimes associated with nausea
Anti-prostaglandins such as NSAIDs can relieve dysmen-
and vomiting, and ginger also works to alleviate these symp-
orrheal pain. Mefenamic acid from fenamate groups and
toms. The efficacy of ginger in treatment of chemotherapy-
ibuprofen from propionic acids act as inhibitors of PGs syn-
induced delayed nausea23 and nausea and vomiting in preg-
thesis.5 The question is why ginger has similar effects as the
nancy and after surgery24,25 has been reported, with minor
other two drugs. In a search of the literature, we found no
side effects.
study that assessed the effects of ginger on dysmenorrhea;
It has been reported that more than 6 g of dry powder of
its use has been been based on traditional sources.15 How-
ginger can cause desquamation of the epithelial cells in the
ever, the effects of other herbs such as fennel,16,18 cumin, and
stomach lining of humans. Therefore, the dosage should be
chamomile on dysmenorrhea have been studied.11 Like other
limited to less than 6 g on an empty stomach.26 It can also
herbs, ginger compounds are very complex and include
result in sensitivity reactions, dermatitis27 and, at high doses,
many substances such as carbohydrates, free fatty acids,
in depression of the nervous system as well as cardiac dys-
amino acids, proteins, phytoesterols, vitamins (niacin), and
rhythmia.28 Although there is no evidence regarding drug
some nonaromatic compounds such as gingerols and
interactivity of ginger,11 NSAIDs, particularly aspirin, have
shogaols.11 Its essence mainly includes sesquiterpene.14 Alt-
the potential to interact with herbal supplements, and fur-
man and Marcussen compared the effects of two ginger
ther research is needed to confirm and assess the clinical sig-
species (Z. officinale and Alpinia galangal; 510 mg twice daily)
nificance of these potential interactions.29
with placebo in patients with knee osteoarthritis and found
There are some limitations to this study. Because ran-
that ginger extract had a significant effect on reducing symp-
domization was not easily possible, patients were alternately
toms of osteoarthritis.19 Salicylate has been found in ginger
allocated into the groups. However, all three groups were
in amounts of 4.5 mg/100 gm fresh root. Therefore, there
similar in baseline characteristics. Although participants
was less than 1mg salicylate in the capsule in the study of
could not determine whether they received a ginger or other
Altman and Marcussen, and this could not explain the ob-
capsule even after examining, smelling, and swallowing it,30
served effects of ginger.19 In fact, ginger inhibits cyclooxy-
questioning participants whether they thought they had re-
genase and lipooxygenase pathways in PGs synthesis.10,13 In
ceived an active treatment or a placebo could specify a dou-
pharmacopoeias, ginger is indicated for dyspepsia, disten-
ble blind setting. We did not assess other possible symptoms

132
OZGOLI ET AL.
associated with dysmenorrhea; that is suggested for future
sion E Monographs: Therapeutic Guide to Herbal Medicines.
studies. Also, using measurements such as the visual ana-
Austin: Lippincott Williams & Wilkins, 1998:136.
logue scale or the numeric rating scale for assessing symp-
13. Kim SO, Kundu JK, Shin YK, et al. [6]-Gingerol inhibits COX-
toms may help to find minimal differences between the
2 expression by blocking the activation of p38 MAP kinase
groups.
and NF-kappaB in phorbol ester-stimulated mouse skin.
Oncogene 2005;24:2558–2567.
Conclusion
14. Mills S, Bone K. Principles and Practice of Phytotherapy:
Modern Herbal Medicine. Edinburgh: Churchill Living-
Ginger is as effective as mefenamic acid and ibuprofen in
stone, 2000:394–400.
relieving pain in women with primary dysmenorrhea. Fur-
15. Ibn-Sina HA. The Canon of Medicine. Farsi translation by
ther studies regarding the effects of ginger on other symp-
Sharafkandi, 5th ed. Tehran: Soroosh, 1991:134.
toms associated with dysmenorrhea, the efficacy and safety
16. Namavar JB, Tartifizadeh A, Khabnadideh S. Comparison
of various doses and treatment durations of ginger, and the
of fennel and mefenamic acid for the treatment of primary
exact mechanism of action are warranted.
dysmenorrhea. Int J Gynaecol Obstet 2003;80:153–157.
17. French L. Dysmenorrhea. Am Fam Physician 2005;71:285–
Acknowledgments
291.
18. Khorshidi N, Ostad SN, Mosaddegh M, Soodi M. Clinical
Our special thanks to students who participated in this
effects of fennel essential oil on primary dysmenorrhea. Iran
study. We thank the staffs of the dormitories of Isfahan and
J Pharmaceut Res 2003;2:89–93.
Shahid Beheshti Universities of Medical Sciences who helped
19. Altman RD, Marcussen KC. Effects of a ginger extract on
us conduct this research, and Ali Gholamrezaei who helped
knee pain in patients with osteoarthritis. Arthritis Rheum
us in writing this report.
2001;44:2531–2538.
20. Kim JK, Kim Y, Na KM, et al. [6]-Gingerol prevents UVB-
Conflicts of interest
induced ROS production and COX-2 expression in vitro and
in vivo. Free Radic Res 2007;41:603–614.
No competing financial interests exist.
21. Lantz RC, Chen GJ, Sarihan M, et al. The effect of extracts
from ginger rhizome on inflammatory mediator production.
References
Phytomedicine 2007;14:123–128.
1. Rapkin AJ, Howe CN. Pelvic Pain and Dysmenorrhea, 14th
22. Grzanna R, Lindmark L, Frondoza CG. Ginger—An herbal
ed. In: Berek JS, ed. Philadelphia: Lippincott Williams &
medicinal product with broad anti-inflammatory actions. J
Wilkins, 2007:506–541.
Med Food 2005;8:125–132.
2. Coco AS. Primary dysmenorrhea. Am Fam Physician 1999;
23. Levine ME, Gillis MG, Koch SY, et al. Protein and ginger for
60:489–496.
the treatment of chemotherapy-induced delayed nausea. J
3. Speroff L, Fritz MA. Clinical Gynecologic Endocrinology
Altern Complement Med 2008;14:545–551.
and Infertility, 7th ed. Philadelphia: Lippincott Williams &
24. Boone SA, Shields KM. Treating pregnancy-related nausea
Wilkins, 2005:540–541.
and vomiting with ginger. Ann Pharmacother 2005;39:1710–
4. Dawood MY. Primary dysmenorrhea: Advances in patho-
1713.
genesis and management. Obstet Gynecol 2006;108:428–441.
25. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, et al.
5. Burke A, Smyth EM, FitzGerald GA. Analgesic-Antipyretic
The efficacy of ginger for the prevention of postoperative
and Antiinflammatory Agents; Pharmacotherapy of Gout.
nausea and vomiting: a meta-analysis. Am J Obstet Gynecol
In: Brunton L, Lazo J, Parker K, eds. Goodman & Gilman’s
2006;194:95–99.
The Pharmacological Basis of Therapeutics, 11th ed. New
26. Desai HG, Kalro RH, Choksi AP. Effect of ginger and garlic
York: McGraw-Hill Professional, 2006:671–716.
on DNA content of gastric aspirate. Indian J Med Res 1990;
6. Proctor ML, Murphy PA. Herbal and dietary therapies for
92:139–141.
primary and secondary dysmenorrhoea. Cochrane Database
27. Futrell JM, Rietschel RL. Spice allergy evaluated by results
Syst Rev 2001;(3):CD002124.
of patch tests. Cutis 1993;52:288–290.
7. Proctor ML, Murphy PA, Pattison HM, et al. Behavioural in-
28. Ginger. Online document at: www.vitamins-supplements.
terventions for primary and secondary dysmenorrhoea.
org/herbal-supplements/ginger.php Accessed December
Cochrane Database Syst Rev 2007 Jul 18;(3):CD002248.
11, 2008.
8. Taylor D, Miaskowski C, Kohn J. A randomized clinical trial
29. Abebe W. Herbal medication: Potential for adverse interactions
of the effectiveness of an acupressure device (Relief Brief)
with analgesic drugs. J Clin Pharm Ther 2002;27:391–401.
for managing symptoms of dysmenorrhea. J Altern Com-
30. Zick SM, Blumea A, Normolle D, Ruffin M. Challenges in
plement Med 2002;8:357–370.
herbal research: A randomized clinical trial to assess blind-
9. Han SH, Hur MH, Buckle J, et al. Effect of aromatherapy on
ing with ginger. Complement Ther Med 2005;13:101–106.
symptoms of dysmenorrhea in college students: A random-
ized placebo-controlled clinical trial. J Altern Complement
Address reprint requests to:
Med 2006;12:535–541.
Marjan Goli, M.Sc.
10. Ali BH, Blunden G, Tanira MO, Nemmar A. Some phyto-
Nursing and Midwifery School
chemical, pharmacological and toxicological properties of
Islamic Azad University of Najafabad
ginger (Zingiber officinale Roscoe): a review of recent re-
University Avenue
search. Food Chem Toxicol 2008;46:409–420.
Isfahan
11. Dermarderosian A, Beutler JA. Review of Natural Products.
Iran
St. Louis: Facts and Comparisons, 2000:243–246.
12. Blumenthal M, Busse WR. The Complete German Commis-
E-mail: [email protected]