Traditional Chinese Medicine (TCM) has been used over thousands of years in China to treat a wide range of diseases including gynecological conditions and help women maintain their health from menarche in adolescence through adulthood to menopausal in elder age. Dysmenorrhoea is one of the most common gynecological symptoms or diseases experienced by women in the reproductive age with a very high prevalence at 70% to 90%, averaging 88% amongst the female population in Australia (Subasinghe et al., 2016; Xu et al., 2019). It can be classified into primary dysmenorrhoea (PD) which implies menstrual pain without identifiable uterine or pelvic pathology; and secondary dysmenorrhoea (SD) due to the pathology of female reproductive system, commonly seen in patients with endometriosis and pelvic inflammatory disease (Zhu et al., 2008). Whilst SD may be effectively treated by eliminating the underlying conditions, PD poses greater challenges in practice since the onset begins soon after menarche without obvious causative factors on which treatment strategies can be based. Therefore, most studies emphasise exploring effective therapies with minimal adverse effects for PD.
The currently recommended WM treatments for PD include NSAIDs and OCP with a relatively high success rate up to 95% and 80% respectively (Liu et al., 2019; Xu et al., 2019). However, the long-lasting analgesic effect cannot be achieved with these drugs and regular use at each menstrual cycle is often required (Kotani et al., 1997). A study suggests that 82% of women were reluctant to take WM pharmaceuticals if they only provide temporary relief of the symptoms without addressing the causes (Subasinghe et al., 2016). Moreover, long term use causes many known adverse effects, including nausea, indigestion and drowsiness from NSAIDs; water retention and metabolic endocrine imbalance from the OCP, resulting in poor compliance (Liu et al., 2019).
TCM with its featured therapies in the form of acupuncture, moxibustion, massage, cupping and dietary therapy has shown proven efficacy for dysmenorrhoea in a review on several studies conducted previously (Xu et al., 2019). Chinese herbal medicine (CHM), as the primary treatment method of TCM, has been found with promising results and superior benefits to the treatment of dysmenorrhoea when used either as individual herbs or combined together in formulas (Daily et al., 2015; Sun et al., 2016; Zhu et al., 2008). More importantly, CHM has less or no known adverse effects based on the current level of study, which justifies the long term use if required. It also targets the causes rather than simply relieving the symptoms of dysmenorrhoea, thereby producing a more sustained effect, compared with other TCM modalities and WM pharmaceuticals (Zhu et al., 2008). Therefore, women nowadays are seeking alternative therapies or non-pharmaceuticals amongst which CHM becomes an increasingly likely treatment option (Jung et al., 2016).
The primary aetiology of PD from WD perspective attributes to the over secretion of prostaglandin (PG) due to hormonal or endocrine imbalance during women’s early age of development (Xu et al., 2019). PG is synthesised in the metabolism of arachidonic acid by the enzyme, cyclooxygenase (COX) (David & James, 2013). PG increases the contractility of uterine smooth muscles, resulting in decreased blood supply and ischemia of uterus while increasing its sensitivity to pain, causing dysmenorrhoea (Kotani et al., 1997; Xu et al., 2019). NSAIDs reduce contraction of the uterus by inhibiting COX and arachidonic acid in the synthesis of prostaglandin, thereby relieving the menstrual pain. OCPs suppress ovulation and the proliferation of the endometrial lining which reduces activity and contractility of uterus, thus reducing the pain (Zhu et al., 2008).
It may be difficult to determine the exact mechanism of action of herbs because it involves a complex component of chemical ingredients and there have been limited researches so far evaluating the biologic ingredients. When it comes to the diagnosis of PD in TCM, there is much more involved in the process of reasoning than simply naming the disease as such in WM. TCM takes PD further to consider other relevant complaints such as the nature of the pain, coldness in lower abdomen, whether the pain occurs before or after period, emotional health and many more, all of which contribute to the final TCM diagnosis. The cluster of symptoms forms syndromes with unique titles such as qi and blood stagnation, cold retention, kidney and liver deficiency which mark the common classifications of PD (Tan, 2016). CHM is then prescribed according to the pattern and further tailored to an individual’s clinical presentation.
A pilot RCT1 by Yeh et al. (2007) on the effect of Si Wu Tang (SWT) for PD revealed statistically significant difference in the VAS pain score and pain intensity in the treatment group as compared to those treated by placebo. However, this positive finding was only observed from the fourth menstrual cycle while the placebo group started an upward trending with the pain. There was no statistically distinct effect from SWT at the end of the 3-month treatment cycle although the same trend persisted during this period. Another trial (Chou et al., 2008) on CHM for PMS concluded with the similar finding that the full effect of CHM can take some time to present as the body responds to the pharmaceutical elements of the herbs. Although the study did not explore the ingredient of SWT from the viewpoint of modern medicine, the formula has been proven to inhibit COX2 and its metabolites up to 85%. This result mimics the NSAIDs in relieving PD but demonstrates marked advantage in terms of sustained effects and no reported side effects (Yeh et al., 2007).
Despite the positive findings and rigorous methodology from this RCT, the result may have been compromised by studying fewer than the anticipated participants due to poor commitment, dropout and stringent selection criteria. Another criticism is that the study deployed a blanket approach by prescribing the same SWT for all participants without differentiating the syndrome pattern of PD from their presented symptoms. It dismissed the key requirement of TCM diagnostic technique when prescribing CHM (Zhu et al., 2008). SWT has the primary function of tonifying blood, therefore is more suitable for PD due to blood deficiency rather than qi blood stagnation, cold stagnation or kidney deficiency (Li & Lian, 2016). It was likely that the included participants may have been given SWT for other patterns than it otherwise is indicated for the syndrome of blood deficiency in PD. This could further diminish the sample size, thereby yielding misleading results with the true effect of SWT underestimated.
Another pilot RCT2 by Kennedy et al. (2006) with 38 participants examined the efficacy and safety of a customed CHM formula for PD, containing Dang Gui, Bai Shao and Yan Hu Suo. The study shared common results with those of RCT1 where the SWT consists of two chief herbs, Dang Gui and Bai Shao which were also used in this experiment. Slightly unlike the findings from RCT1, CHM group showed no statistically significant benefit over the placebo in any set outcome measures across the study period. However, after the third treatment cycle 53% women treated by CHM experienced less pain compared with only 26% women in the placebo, which is a substantial difference, yet statistically insignificant with P=0.10. The result coincides with the previous findings that herbal ingredients may have a cumulative and sustained effect in light of the core features of TCM which target the root cause, regulate zang fu organs and restore the imbalance of yin and yang as a whole (Chou et al., 2008). Likewise, there are no obvious adverse effects from CHM treatment apart from some headache which is reported in both groups. However, as for future studies, a longer treatment course may be necessary to observe the safety of CHM with sustained ingestion. Both RCTs confirmed the progressive decrease trend in the use of NSAIDs, Ibuprofen in both groups throughout the treatment course with the CHM group in RCT2 reports using even lower dose in one cycle, but again not statistically significant. There may be a component of psychological comfort with the continuous use of the pharmaceutical even if the proposed TCM therapy may have produced equally effective relief of their symptoms.
This trial followed the methodology and Cochrane design to conduct an RCT, but the results are reported in a simplified version of standard RCTs as it only contains three pages. It lacks detailed discussion of the findings and did not include essential figures which summarise the data analysis. The active compounds of each herb were explained along with the pharmacological effects, in which people with a science-based mind may find more accepted. The study is disadvantaged by a very few participants following further dropout and withdrawal, which is justified by the authors as the formal sample size calculation being not required in a pilot study. They were hopeful of advanced RCTs to be carried out based on their calculation that 260 subjects in each group would be required to detect the true effect of CHM for PD.
An important implication to clinical practice as it rises from this RCT as it did with the previous study is implementing the tailored approach of TCM theory when composing a herbal formula for patients. The formula is then prescribed based on the syndrome pattern differentiation with modification made to individual clinical presentation (Zhu et al., 2008). It is also important to note that the pattern is constantly evolving as the condition changes with the treatment. Therefore, the formula needs to be altered accordingly throughout the treatment course. Unfortunately, the experimental formula in this study was applied to the treatment group regardless of TCM patterns and maintained without modification. Although either an excess or deficient pattern can be indicated by Dang Gui, Bai Shao and Yan Hu Suo, the study results could still be misled, especially with Yan Hu Suo which invigorates qi and blood and is more suitable for PD due to excess (Bensky et al., 2004).
The RCT3 by Kotani et al. (1997) examined the effect of Dang Gui Shao Yao San (TSS) for PD by recruiting women with the corresponding TCM patterns. After observation for two cycles, patients receiving TSS experienced significant relief of menstrual pain compared with placebo straight after the first cycle of active treatment. This testifies that herbal formulas tailored to their indicated patterns and symptoms provide more rapid and effective relief of pain for PD (Zhu et al., 2008). The effect of CHM lasted to the follow-up period, which is consistent with the previous RCTs. The use of NSAIDs in the treatment group was significantly reduced (p<0.05) while this finding was reported in RCT1 and 2, but not statistically remarkable. Similarly, no serious side effects were experienced by patients during and after CHM treatment.
Although the findings are promising and invaluable to convince a broader application of CHM for PD, the study was carried out in 1997 and it may be outdated and no longer applicable to contemporary settings. The study followed basic RCT guidelines in its structure but flawed by the poor recognition of potential bias and other limitations, and anticipation for future researches. Once again, the true value of TSS may not be fully represented due to the equally low sample size of 40 in this study, which is a common issue across all the RCTs on CHM.
Current researches remain conservative about the positive findings on CHM for PD due to the low quality of study, very small sample size, and improper risk of bias control. Future trials shall carefully modify the design and methods into the style that suits exclusively to the requirement for studying CHM, concerning the alignment of TCM syndromes of participants with the proposed herbal treatment, and study of the combined action of multiple herbs in a formula rather than single herb for a condition. Trials featuring these key characters with larger sample size, longer observation phase and improved methodology are required to confirm the definitive efficacy and safety of CHM for PD. Although current RCTs reached the consensus that CHM is generally considered to be safe, as with all forms of medicines, it may carry a level of risk in terms of possible adverse reactions in individual cases if not used correctly (AHPRA, 2019). As far as the study results presented from the RCTs, this review discovered promising evidence that CHM can be an effective and safe form of therapy to help women manage PD when used properly by qualified practitioners, and according to the TCM diagnostic theory.
References
RCT1: Yeh, L. L. L., Liu, J.-Y., Lin, K.-S., Liu, Y.-S., Chiou, J.-M., Liang, K.-Y., . . . Huang, C.-Y. (2007). A randomised placebo-controlled trial of a traditional Chinese herbal formula in the treatment of primary dysmenorrhoea. PLoS ONE, 2(8), e719. doi:10.1371/journal.pone.0000719
RCT2: Kennedy, S., Jin, X., Yu, H., Zhong, S., Magill, P., Van Vliet, T., . . . Pasman, W. (2006). Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea. Fertility and Sterility, 86(3), 762-764. doi:10.1016/j.fertnstert.2006.02.092
RCT3: Kotani, N., Oyama, T., Sakai, I., Hashimoto, H., Muraoka, M., Ogawa, Y., & Matsuki, A. (1997). Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea-A double-blind study. The American journal of Chinese medicine, 25(02), 205-212. doi:10.1142/s0192415x9700024x
AHPRA., Chinese Medicine Board of Australia. (2014). Guidelines for advertising regulated health services. Retrieved from https://www.chinesemedicineboard.gov.au/Codes-Guidelines/Advertising-a-regulated-
AHPRA., Chinese Medicine Board of Australia. (2019). Social media: How to meet your obligations under the National Law. What are the common pitfalls when using social media? Retrieved from
AHPRA., Chinese Medicine Board of Australia. (2020). Codes and Guidelines. Retrieved from
Bensky, D., Clavey, S., Gamble, A., Stöger, E., & Bensky, L. L. (2004). Chinese herbal medicine materia medica
(3rd ed.). Seattle, WA: Eastland Press.
Chou, P. B., Morse, C. A., & Xu, H. (2008). A controlled trial of Chinese herbal medicine for premenstrual syndrome. Journal of Psychosomatic Obstetrics and Gynaecology, 29(3), 189-196. doi:10.1080/01674820801893011
Daily, J. W., Zhang, X., Kim, D. S., & Park, S. (2015). Efficacy of ginger for alleviating the symptoms of primary dysmenorrhea: A systematic review and meta‐analysis of randomized clinical trials. Pain Medicine, 16(12), 2243-2255. doi:10.1111/pme.12853
David, O. N., & James, A. C. (2013). Chapter 3: Synthesis, metabolism, and actions of bioregulators. In Vertebrate Endocrinology (Fifth ed., pp. 41-91): Elsevier Inc. doi:10.1016/B978-0-12-394815-1.00003-3
Jung, J., Lee, J. A., Ko, M. M., You, S., Lee, E., Choi, J., . . . Lee, M. S. (2016). Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with uterine fibroids: A protocol for a randomised controlled trial. BMJ Open, 6(11). e013440. doi:10.1136/bmjopen-2016-013440
Li, J., & Lian, J. W. (2016). Chinese herbal medicine formula (10th ed.). Beijing, China: China TCM Publication.
Liu, Y.-H., Sun, J., Shi, L., Yan, Y., & Wang, X. (2019). Effect of herb-partitioned moxibustion for primary dysmenorrhea: A randomized clinical trial. Journal of Traditional Chinese Medicine, 39(2), 237-245.
Subasinghe, A. K., Happo, L., Jayasinghe, Y. L., Garland, S. M., & Wark, J. D. (2016). Prevalence and severity of dysmenorrhoea, and management options reported by young Australian women. Australian Family Physician, 45(11), 829-834.
Sun, L., Liu, L., Zong, S., Wang, Z., Zhou, J., Xu, Z., . . . Kou, J. (2016). Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrhea via attenuating uterus contraction. Journal of Ethnopharmacology, 191, 273-279. doi:https://doi.org/10.1016/j.jep.2016.06.042
Tan, Y. (2016). Traditional Chinese medicine in gynaecology (10th ed.). Beijing, China: China TCM Publication.
Xu, L., Xie, T., Shen, T., & Zhang, T. (2019). Effect of Chinese herbal medicine on primary dysmenorrhea: A protocol for a systematic review and meta-analysis. Medicine, 98(38), e17191. doi:10.1097/MD.0000000000017191
Zhu, X., Proctor, M., Bensoussan, A., Wu, E., & Smith, C. A. (2008). Chinese herbal medicine for primary dysmenorrhoea. Cochrane Database of Systematic Reviews(2). doi:10.1002/14651858.CD005288.pub3