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Behmanesh E, Delavar MA, Kamalinejad M, Khafri S, Shirafkan H, Mozaffarpur SA. Effect of Eryngo (Eryngium caucasicum Trautv) on primary dysmenorrhea: a randomized, double-blind, placebo-controlled study.Taiwan J Obstet Gynecol. 2019;58:227-233.
Learning objectives
To study the effects of a traditional Iranian herbal medicine, Eryngo (Eryngium caucasicum) for primary dysmenorrhea compared to ibuprofen and placebo for primary dysmenorrhea within 1-2 years after menarche
Draft
Three-arm, double-blind, placebo-controlled study
Participant
One hundred and sixty-nine women with confirmed primary dysmenorrhea
Inclusion criteria
Females aged 15 to 30 years, not pregnant, regular menstruation (cycle of 21 to 35 days), menstrual bleeding of 3 to 7 days in the last 6 months, dysmenorrhea lasting 8 to 72 hours, graded as Grade 1 or moderate to strictly on the Verbal Multidimensional Scoring System (VMSS)
Exclusion criteria
Secondary dysmenorrhea; Pregnancy; being a professional athlete; mild dysmenorrhea; irregular menstruation; severe causes of stress (family disputes, death of parents); medication intake; abnormal pelvic and/or abdominal findings on ultrasound; History of pelvic surgery
Instruments
VMSS, baseline questionnaire on age, menstrual cycle, degree of dysmenorrhea, visual analogue scale (VAS) for measuring dysmenorrhea, use of paracetamol for dysmenorrhea
Treatment
There were 3 treatment groups: Eryngo simple syrup, 5 mL TID; Ibuprofen syrup, 200 mg three times daily; and placebo simple syrup, 5 mL TID. Each treatment started on day 1 of menstruation and lasted 5 days for 2 menstrual cycles.
analysis
SPSS (version 21) for descriptive statistics, repeated measures analysis of variance and NNT (Number Needed to Treat). It was made importantP≤0.05.
Key insights
The mean age of the study participants was 19.5 ± 5 years; the mean BMI was 21.6 ± 3.8 kg/m2. The mean age of menarche was 12.6 ± 1.2 years, the mean menstrual duration was 6.9 ± 1.3 days, and the mean menstrual cycle length was 29.1 ± 5.4 days. These are normal findings for this age group.
Peak pain based on VAS was significantly reduced in the first and second menstrual cycles compared to the pretreatment cycle (P<0.0001): 4.2 for Eryngo, 4.3 for ibuprofen and 0.9 for placebo (P<0.0001). This decrease in pain intensity persisted for the subsequent menstrual cycle when treatment was discontinued; however, pain increased in the placebo group.
In this study, Eryngo was shown to be effective in relieving primary dysmenorrhea after 2 cycles.
Based on the pain level in the second menstrual cycle treated, the NNT was 1.5 for Eryngo and 2.0 for ibuprofen. The NNT for Eryngo in combination with ibuprofen was approximately 6.0 according to the authors, although the calculation of the combined NNT value was not described.
No serious adverse events were reported in any of the 3 groups. Five of the 136 subjects reported gastric reflux, nausea, vomiting, and menorrhagia, but the differences between treatment groups were not statistically significant. Treatment satisfaction was 70.2%, 39.4%, and 7.0% in the eryngo, ibuprofen, and placebo groups, respectively; 89.4%, 84.7% and 37.2%, respectively, would recommend their treatment (P=0.0001). Dissatisfaction rates were 8.5%, 4.3%, and 79.0%, respectively (P=0.0001).
The total phenolic content of Eryngo syrup was 35 μg/mL (9.72% herbal extract); The total flavonoid content was 27 μg/ml (7.5% herbal extract). Thus, a 100 ml bottle of syrup contained 9.72 mg of phenols and 7.5 mg of flavonoids, which corresponds to almost 525 μg of phenols and 135 μg of flavonoids per daily treatment. The Eryngo comes from a breeder in Babol, Mazandaran, Iran; the placebo and ibuprofen syrups were manufactured by Soha Pharmaceutical Company. A professor of pharmacognosy at Shahid Beheshti University of Medical Sciences, Iran, confirmed the identity of the Eryngo samples before they were prepared.
Practice implications
Eryngo is a traditional herb used in northern Iran. It is served with fish and chicken and used to flavor pickles and other dishes. Its taste is pronounced and is somewhat reminiscent of coriander.
In this study, Eryngo was shown to be effective in relieving primary dysmenorrhea after 2 cycles. The plant is typically used for asthma, bronchitis and epigastric pain. This evidence suggests that it is anti-inflammatory, particularly given its phenols and flavonoids content, and may have a beneficial effect on spastic smooth muscles. Unfortunately, the study authors did not identify its components in detail nor indicate whether they tried to mask its taste or adjust the placebo and ibuprofen syrups to mimic the taste of Eryngo.
The genusEryngiumcontains 250-300 species and is considered the largest and most complex in the worldApiaceaeFamily.1The different plant species contain flavonoids, tannins, saponins and triterpenoids. Eryngial is an essential oil common to this genus and is known to have antibacterial effects in the presence ofStaphylococcus aureus,Klebsiella pneumoniae,Proteus mirabilisand the third stage larvae ofStrongyloides stercoralis.2.3 E caucasicumalso contains essential oils of 4(5)-acetyl-1H-imidazole, thymol, sesquiphellandrene, limonene and trans-β-farnesene.1The flavonoid content includes quercetin at 12.5–100 μg/mL, but the remaining flavonoids were not identified. The plant therefore has good antioxidant properties.4
A systematic review of all clinical trials of herbs for primary dysmenorrhea was published in 2014.5Exclusion criteria were mild dysmenorrhea, irregular menstruation, and commitment to use any medication for treatment.5All included studies had to have a Jadad score ≥ 3. 25 studies were subjected to intensive review. The top botanicals and number of articles wereFoeniculum vulgare(8),Mentha piperita(1),Zataria multiflora(1),Valerian officinalis(2),Cinnamomum zeylanicum(1),Zingiber officiale(2),Matricaria chamomileone (1),Stachys lavandulifolia(2),Echinophora platyloba(1),Vitex agnus castus(1), Menstrogol® (2), Menastil® (1) andAchillea wilhelmsii(1).5
In all attemptsF. vulgare (Apiaceae)– probably its essential oils – was comparable in effectiveness to mefenamic acid.5 Z officinale(Zingiberaceae), which inhibits cyclooxygenase, was as effective as ibuprofen and mefenamic acid. Menastil®, which containsMarigold officinalis(Asteraceae) andM Piperita(Mint family) essential oil, prevents the transmission of nerve signals and was more effective than placebo in reducing menstrual bleeding.Cumminum cyminum(Apiaceae) was as effective as mefenamic acid, but no mechanism of action was described. Menstrogol® (saffron, celery and anise) was superior to mefenamic acid; essential oils may be its mechanism of action.M chamomile(Asteraceae) alone reduced menstrual anxiety and was superior to mefenamic acid for pain control; when combined withF vulgar, it reduced pelvic and abdominal pain, depression and anger. Mechanism of action has not been described.V officinalis(Caprifoliaceae) has an antispasmodic effect on smooth muscles, inhibits contractions of cell depolarization and blocks calcium channels. It was comparable to mefenamic acid in one study, but only comparable to placebo in another study.C. zeylanicum(Laurel family) has essential oils that are antispasmodic and inhibit the biosynthesis of inflammatory prostaglandins; its effects were significantly better than placebo.S lavandulifolia(Mint family), which inhibits prostaglandins, reduced muscle spasms and was comparable to placebo; in another study, it reduced the duration and severity of dysmenorrhea pain.Z Multiflora(Mint family) contains essential oils and flavonoids that inhibit contractions and block calcium channels. The best effect was with 2% essential oil; The use of its leaves was comparable to mefenamic acid.M Piperita(Mint family) essential oil reduced smooth muscle contractions and was comparable to ibuprofen.Vitex agnus castus(Mint family) has dopaminergic effects that make it more effective than placebo.E platyloba(Apiaceae) reduced muscle contractions more than placebo; when compared withF vulgarthe latter was more effective.A Wilhelmsii(Asteraceae) Flavonoids have antiprostaglandin effects and inhibit arachidonic acid metabolism, which reduces dysmenorrhea pain.5
Few botanicals have been evaluated in more than 1 or 2 studies for primary dysmenorrhea or against conventional pharmaceutical treatments.Eryngiumis no exception. What is interesting is that theApiaceae,AsteraceaeandMint familyare the most common plant families from which effective plant compounds have been identified; probable mechanisms of action may be mainly 3 or 4 in number. This author has experience with about two-thirds of the herbs tested, although not always for dysmenorrhea, and would be willing to try itEryngiumif a reliable source could be found. However, exercise, diet, stress reduction, and hormone balancing are also important for treating primary dysmenorrhea. This study adds another traditional plant to the list of those that can treat primary dysmenorrhea.
The article was well written, but I was disappointed with the componentsEryngium caucasicumin the treatment syrup were not characterized in more detail. The calculation of the components is not fully explained in the publication, but I provide total amounts of phenol and flavonoids per day based on the authors' initial calculation of the components. Characterizing the components would help us better understand possible mechanisms of action.
The somewhat positive response to the simple syrup placebo may be due in part to its sweet taste rather than its clinical effect, as it was manufactured in accordance with the United States Pharmacopeia and does not match the taste of the syrups in the other two treatment arms.
The calculation of phenols and flavonoids per daily dose and the calculation of NNT were not shown and do not agree with my calculations of the same. Finally, while the effects of the herb lasted in an untreated menstrual cycle, from a clinical perspective one would like to know how long this effect lasted as this may assist in prescribing to patients.
Summary
E caucasicum, a traditional Iranian and Middle Eastern herbal remedy prepared as a syrup, was compared with ibuprofen syrup and placebo syrup for primary dysmenorrhea. It significantly reduced the pain of primary dysmenorrhea after 2 menstrual cycles and was effective for the third cycle without treatment. It was just as effective as ibuprofen.