The effect of Glycyrrhiza glabra L. on Primary Dysmenorrhea compared with Ibuprofen: A randomized, triple-blind controlled trial

Document Type : Research article


1 Department of traditional medicine, Faculty of Iranian Traditional Medicine, Shahid Sadoughi University of medical sciences, Yazd, Iran.

2 Department of Obstetrics- Gynecology and Infertility, Vali-e-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Biostatistics, Medicinal Plant Research Center, Shahed University, Tehran, Iran.

4 Department of traditional medicine, Faculty of Iranian Traditional Medicine, shahid Sadoughi University of medical sciences, Yazd, Iran.

5 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Primary dysmenorrhea is a common gynecological disorder in women of reproductive age. Despite the effective treatments such as nonsteroidal anti-inflammatory drugs and oral contraceptives, researchers have always been looking for alternative drugs due to the adverse effects and limited efficacy of conventional medications. Glycyrrhiza glabra L. (G. glabra), commonly known as Licorice, has been applied for a long time as a plant with multiple therapeutic potencies in Traditional Persian Medicine (TPM). This study was designed to evaluate the effect of the G. glabra on primary dysmenorrhea.
Sixty patients with moderate and severe dysmenorrhea were randomly divided into two groups; one group received 400 mg Ibuprofen tablets every 8 hours and placebo syrup and the other received 5 cc of G. glabra syrup two times a day and placebo tablets. The patients took the drugs from the first day of menstruation to fifth for two consequent cycles. The primary pain intensity and its changes evaluated in each group and compared between two groups.
Results: The reduction of pain intensity was 5.85 (±3.11) in the G. glabra group compared with 6.92 (±1.87) in the Ibuprofen group (p < 0.001). No significant difference detected between the two groups (p = 0.151). No serious side effects were reported during the study.
Conclusion: This study suggests that we can use G. glabra to relieve the pain in patients with primary dysmenorrhea; although studies with a larger sample size may lead to more comprehensive perceptions about the efficacy of G. glabra.


Main Subjects

(1) Dawood MY. Dysmenorrhea. Clin. Obstet. Gynecol.
(1990) 33: 168-78.
(2) Rapkin AJ and Nathan L. Pelvic Pain and
dysmenorrhea, in Berek & Novak’s Gynecology,
J.S. Berek, Editor. Lippincott Williams and Wilkins:
Philadelphia (2012) p. 481-2.
(3) Dawood MY. Primary dysmenorrhea: advances in
pathogenesis and management. Obstet. Gynecol.
(2006) 108: 428-41.
(4) Jabbour H and Sales K. Prostaglandin receptor
signaling and function in human endometrial
pathology. Trends Endocrinol. Metab. (2004) 15:
(5) Milsom I, Minic M, Dawood MY, Akin MD,
Spann J, Niland NF and Squire RA. Comparison
of the efficacy and safety of nonprescription doses
of naproxen and naproxen sodium with ibuprofen,
acetaminophen, and placebo in the treatment of
primary dysmenorrhea: a pooled analysis of five
studies. Clin. Ther. (2002) 24: 1384-400.
(6) Daniels S, Torri S and Desjardins P. Valdecoxib
for Treatment of Primary Dysmenorrhea, A
Randomized, Double-blind Comparison with
Placebo and Naproxen. J. Gen. Intern. Med. (2005)
20: 62–7.
(7) Edwards JE, Moore RA and McQuay HJ. Rofecoxib
for dysmenorrhoea: meta-analysis using individual
patient data. BMC Women’s Health. (2004) 4: 5.
(8) Zhu X, Proctor M, Bensoussan A, Wu E and
Smith CA. Chinese herbal medicine for primary
dysmenorrhoea. The Cochrane Library (2008).
(9) Proctor M and Murphy PA. Herbal and dietary
therapies for primary and secondary dysmenorrhoea.
Cochrane Database Syst. Rev. (2001) 3: CD002124.
(10) Armanini D, Fiore C, Mattarello M, Bielenberg J
and Palermo M. History of the endocrine effects
of licorice. Exp. Clin. Endocrinol. Diabetes (2002)
110: 257-61.
(11) Jia J, Li Y, Lei Z, Hao Y, Wu Y, Zhao Q, Wang H,
Ma L, Liu J and Zhao C. Relaxative effect of core
licorice aqueous extract on mouse isolated uterine
horns. Pharm. Biol. (2013) 51: 744-8.
(12) Shibata T, Morimoto T, Suzuki A, Saito H and
Yanaihara T. The effect of Shakuyaku-kanzo-to
on prostaglandin production in human uterine
myometrium. Nihon Sanka Fujinka Gakkai Zasshi
(1996) 48: 321-7.
(13) Gupta V, Fatima A, Faridi U, Negi A, Shanker K,
Kumar J, Rahuja N, Luqman S, Sisodia B, Saikia
D, Darokar M and Khanuja S. Antimicrobial
potential of Glycyrrhiza glabra Linn roots. J.
Ethnopharmacol. (2008) 116: 377-80.
(14) Nitalikar MM, Munde KC, Dhore BV and
Shikalgar SN. Studies of antibacterial activities
of Glycyrrhiza glabra root extract. Int. J. Pharm.
Tech. Res. (2010) 2: 899-901.
(15) Hojo H and Sato J. Antifungal activity of licorice
(Glycyrrhiza glabra) and potential applications in
beverage. Foods Food Ingredients J. (2002) 203:
(16) Anderson D and Smith W. The antitussive activity
of glycyrrhetinic acid and its derivatives. J. Pharm.
Pharmacol. (1961) 13: 396-404.
(17) Kalsi S, Verma SK, Neha AK and Singh N. A
review on Glycyrrhiza glabra (Liquorice) and its
pharmacological activities. Int. J. Pharm. Drug
Anal. (2016) 4: 234-9.
(18) Murray WJ. Herbal Medications for
Gastrointestinal Problems, in Herbal Medicinal:
A Clinician s Guide, L.G. Miller and W.J. Murray,
Editors. Pharmaceutical Products Press: New York
(1998) p. 79-93.
(19) Mills S and Bone K. Principles and practice of
phytotherapy. Modern herbal medicine. Churchill
Livingstone (2000).
(20) Herold A, Cremer L, Calugăru A, Tamaş V, Ionescu
F, Manea S and Szegli G. Antioxidant properties
of some hydroalcoholic plant extracts with
antiinflammatory activity. Roum Arch Microbiol.
Immunol. (2003) 62: 217-27.
(21) Siracusa L, Saija A, Cristani M, Cimino F,
D’Arrigo M, Trombetta D, Rao F and Ruberto
G. Phytocomplexes from liquorice (Glycyrrhiza
Jafari Z et al. / IJPR (2019), 18 (Special Issue): 291-301
glabra L.) leaves—Chemical characterization and
evaluation of their antioxidant, anti-genotoxic and
anti-inflammatory activity. Fitoterapia (2011) 82:
(22) Yamaguchi T and Watanabe T. Effects of triterpenes
on the mutagenicities of various mutagens toward
Salmonella. Agric. Biol. Chem. (1984) 48: 3137-9.
(23) Ambawade SD, Kasture VS and Kasture SB.
Anticonvulsant Activity of roots and rhizomes of
Glycyrrhiza glabra Linn. Indian. J. Pharmacol.
(2002) 34: 251-5.
(24) Dhingra D, Parle M, and Kulkarni S. Memory
enhancing activity of Glycyrrhiza glabra Linn in
mice. J. Ethnopharmacol. (2004) 91: 361-5.
(25) Molhuysen JA, Gerbandy J, de Vries LA, de
Jong JC, Lenestra JB, Turner KB and Borst JG.
A licorice extract with desoxycorticosterone like
effect. Lancet (1950) 2: 381-6.
(26) Strong JA. Serum potassium deficiency during
treatment with PAS and liquorice extract. Brit.
Med. J. (1951) 4378: 998-1002.
(27) Groen J, Pelsner H, Willebrands AF and Kamminga
CE. Extract of liquorice for the treatment of
Addison’s distese. N. Engl. J. Med. (1951) 244:
(28) Tamir S, Eizenberg M, Somjen D, Stern N, Shelach
R and Vaya J. Estrogenic and antiproliferative
properties of glabridin from licorice in human
breast cancer cells. Cancer Res. (2000) 60: 5704-9.
(29) Takahashi K, Yoshino K, Shirai T, Niwshigaki A,
Araki Y and Kitao M. Effect of traditional herbal
medicine (shakuyaku-kazo-to) on testosterone
secretion in patients with polycystic ovary
syndrome detected by ultrasound. Nihon Sanka
Fujinka Gakkai Zasshi (1988) 40: 7898-902.
(30) Werner S, Brismar K and Olsson S.
Hyperprolactinemia and liquorice. Lancet (1979)
1: 319.
(31) Chandrasekaran CV, Deepak HB, Thiyagarajan
P, Kathiresan S, Sangli GK, Deepak M and
Agarwal A. Dual inhibitory effect of Glycyrrhiza
glabra (GutGardTM) on COX and LOX products.
Phytomedicine (2011) 18: 278–84.
(32) Kwon H-S, Park JH, Kim DH, Kim YH, Park JHY,
Shin H-K and Kim J-K. Licochalcone A isolated
from licorice suppresses lipopolysaccharidestimulated inflammatory reactions in RAW264. 7
cells and endotoxin shock in mice. J. Mol. Med.
(2008) 86: 1287-95.
(33) Sato Y, He J-X, Nagai H, Tani T and Akao
T. Isoliquiritigenin, one of the antispasmodic
principles of Glycyrrhiza ularensis roots, acts in the
lower part of intestine. Biol. Pharm. Bull. (2007)
30: 145-9.
(34) Shi Y, Wu D, Sun Z, Yang J, Chai H, Tang L and
Guo Y. Analgesic and Uterine Relaxant Effects
of Isoliquiritigenin, a Flavone from Glycyrrhiza
glabra. Phytotherapy Res. (2012) 26: 1410–7.
(35) Momeni A, Rahimian G, Kiasi A, Amiri M and
Kheiri S. Effect of licorice versus bismuth on
eradication of Helicobacter pylori in patients with
peptic ulcer disease. Pharmacognosy Res. (2014)
6: 341-4.
(36) Rahnama M, Mehrabani D, Japoni S, Edjtehadi
M and Firoozi MS. The healing effect of licorice
(Glycyrrhiza glabra) on Helicobacter pylori
infected peptic ulcers. J. Res. Med. Sci. (2013) 18:
(37) Reuters T, PDR for Herbal Medicine. 4th ed., New
York: NY: Thomson Reuters (2007).
(38) Jabbari M, Hashempur MH, Emami Razavi SZ,
Raeisi Shahraki H, Kamalinejad M and Emtiazy
M. Efficacy and short-term safety of topical Dwarf
Elder (Sambucus ebulus L.) versus diclofenac for
knee osteoarthritis: A randomized, double-blind,
active-controlled trial. J. Ethnopharmacol. (2016)
188: 80-6.
(39) Kaur C and Kapoor H. Anti-oxidant activity and
total phenolic content of some Asian vegetables.
Int. J. Food Sci. (2002) 37: 153–61.
(40) Khiveh A, Hashempur MH, Shakiba M, Lotfi MH,
Shakeri A, Kazemeini S, Mousavi Z, Jabbari M,
Kamalinejad M and Emtiazy M. Effects of rhubarb
(Rheum ribes L.) syrup on dysenteric diarrhea in
children: a randomized, double-blind, placebocontrolled trial. J. Integr. Med. (2017) 15: 365-72.
(41) Andersch B and Milsom I. An epidemiologic
study of young women with dysmenorrhea. Am. J.
Obstet. Gynecol. (1982) 144: 655–60.
(42) Rahnama P, Montazeri A, Huseini HF, Kianbakht
S and 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.
(43) Carlsson AM. Assessment of chronic pain. I.
Aspects of the Reliability and Validity of the Visual
Analogue Scale. Pain (1983) 16: 87–101.
(44) Speroff L and Fritz M. Clinical gynecologic
endocrinology and infertility. 7th ed. Philadelphia:
Lippincott Williams and Wilkins (2005).
(45) Dawood MY. Dysmenorrhoea: Clinical Evidence
with Piroxicam-β-cyclodextrin. Clin. Drug
Investig. (2000) 19: 37-40.
(46) Marjoribanks J, Proctor M, Farquhar C,
Sangkomkamhang US and Derks RS.
Nonsteroidal anti-inflammatory drugs for primary
dysmenorrhoea. Cochrane Database Syst. Rev.
(2003) 4. 
Effect of G. glabra on primary dysmenorrhea
(47) Morrison JC, Ling FW, Forman EK, Bates GW,
Blake PG, Vecchin TJ, Linden CV and O’Connell
MJ. Analgesic efficacy of ibuprofen for treatment
of primary dysmenorrhea. South. Med. J. (1980)
73: 999–1002.
(48) Zhang W and Li Wan Po A. Efficacy of minor
analgesics in primary dysmenorrhoea: a systematic
review. BJOG (1998) 105: 780-9.
(49) Avicenna. The Canon of Medicine (Al-Qanon fi alTibb). Beirut, Lebanon: Dar Ihyaa al-Turaath alArabi (2005) [in Arabic].
(50) Aghili SMH. Gharabadin Kabir. 1st edition.
Esfahani MM (ed). Tehran: Iran University of
Medical Sciences, Institute of History of Medicine
Studies and Islamic Medicine. (2009) [in Persian].
(51) Rhazes (Razi MZ). Al-Hawi fi Tibb. Taaimi HK
(ed). Beirut: Dar Ihyaa al-Turaath al-Arabi. (2002)
[in Arabic].