Evaluation of the Synergism of Medicinal Effects of Chamomile and Ginger on Pain and Symptoms of Primary Dysmenorrhea: A Randomized Controlled Trial

* Corresponding Author: Mohammad Ali Zareian, PhD. Address: Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. Tel: +98 (913) 1589919 E-mail: dr.m.a.zareian@gmail.com 1. Department of Midwifery, School of Medicine, Arak University of Medical Sciences, Arak, Iran. 2. Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh Shabani1 , *Mohammad Ali Zareian2


Introduction
ysmenorrhea is one of the most common menstrual disorders that reduce the Quality of Life and disruption in women's social and occupational activities [3]. The prevalence of dysmenorrhea in Iran is about 71% [4]. The first line of treatment for dysmenorrhea are D Non-Steroidal Anti-inflammatory Drugs (NSAIDs), but in addition to NSAIDs, several oral and non-oral therapies have been suggested for primary dysmenorrhea but there is still insufficient evidence to support their efficacy [5].
Studies on the effects of chamomile, ginger, and honey on dysmenorrhea have been carried out separately [15,21,28], but no study was done on the simultaneous administration of these three cases and their possible synergism. The purpose of this study was to evaluate the effect During the study, 23 patients were excluded because of not completing the questionnaire, marrying, unwillingness to continue, and discontinuing medication. Overall, the reported side effects of the drugs were skin allergy (n=17), gastrointestinal side effects (n=18), and hot flash (n=9). Most of the complications were related to the ginger group; there was no statistically significant difference between the groups in terms of complications.
The mean age of the samples was 21.002±1.91 years and they were between 18-30 years old. Demographic indices and menstrual characteristics were not significantly different between groups, except for the mean age in the chamomile group and menstrual cycle length in the ginger group (Table 1). The severity of pain, number of days of pain, low back pain, amount of analgesia, total symptom score, and bleeding rate were significantly decreased in all 4 groups (P=0.001). No significant differences were observed except for the difference in total symptom score and bleeding rate between groups.
The combination of ginger-chamomile did better in reducing overall symptom score than other interventions (P=0.02). Mefenamic acid also had a better effect on reducing bleeding than other interventions (P=0.008). Ginger group had the highest effect on fatigue reduction (P=0.02).

Discussion
So far, no study has investigated the effect of gingerchamomile and honey on dysmenorrhea. In the case of distilled extracts, we should expect some chemical interactions to occur between the compounds. The decoction may alter the amount of active ingredient extraction or produce new compounds, which may exhibit new medication [42]. Combination of medicines is usually aimed at increasing efficacy and reducing complications, but not every combination results in synergism [41].
Considering the total pain experienced by dysmenorrhea patients, i.e., low back pain and headache, all four interventions had similar effects in controlling pain severity, reducing pain-killing consumption, and reducing back pain but did not have significant effect on ginger-chamomile group headaches; chamomile did better than mefenamic acid, as confirmed by previous studies [32]. The combination of chamomile and ginger does not seem to be superior to chamomile in controlling the pain experience of a patient with dysmenorrhea.
In the present study, although chamomile did better in controlling pain, but ginger-chamomile did better in controlling mood symptoms and ginger did better in controlling fatigue. Given that one of the mechanisms involved in the onset of mood symptoms is the relative decrease in serotonin in the menstrual cycle [36], the role of ginger in controlling these symptoms can be justified because ginger also contains compounds that are agonists of a group of serotonin receptors [37]. Taken together, the results suggest that combining ginger and chamomile does not cause synergy or reduce drug side effects, and this combination is not significantly superior to ginger or chamomile with honey for the treatment of dysmenorrhea.

Compliance with ethical guidelines
This project was registered (Code of Ethics: ARAKMU. REC.1395.164) by the Ethics Committee of Arak University of Medical Sciences and Code N52016100825031 at the Clinical Trials Registration Center.

Funding
All the expenses of this project have been provided by the research deputy of Arak University of Medical Sciences.

Conflicts of interest
The authors declared no conflict of interest.