Journal of Ethnopharmacology 152 (2014) 314–319
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Research Paper
The traditional Chinese medicine prescription pattern of patients with primary dysmenorrhea in Taiwan: A large-scale cross sectional survey Jung-Chuan Pan a, Yueh-Ting Tsai a, Jung-Nien Lai a,b,n, Ruei-Chi Fang c, Chia-Hao Yeh b a
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei 111, Taiwan c Department of Pharmacy, China Medical University Hospital, Taichung 404, Taiwan b
art ic l e i nf o
a b s t r a c t
Article history: Received 19 November 2013 Received in revised form 31 December 2013 Accepted 2 January 2014 Available online 10 January 2014
Ethnopharmacological relevance: Traditional Chinese medicine (TCM), when given for symptom relief, has gained widespread popularity among women with primary dysmenorrhea (PD). The aim of this study was to analyze the utilization of TCM among PD women in Taiwan. Methods: The use, service frequency and Chinese herbal products prescribed for PD women were evaluated using a cross sectional survey of 23,118 beneficiaries who were recruited from the National Health Insurance Research Database. The logistic regression method was employed to estimate the odds ratios (ORs) for utilization of TCM. Results: Overall, 53.4% (N ¼12,349) of PD women utilized TCM and 92.2% of them sought TCM with the intention of treating their menstruation-related pain symptoms. PD women who do not take prescription painkillers (aOR ¼35.75, 95% CI:33.20–38.49) were more likely to seek TCM treatment than those who took pain medication (aOR ¼1.00). There were a total of 213,249 TCM visits due to PD, of which more than 99% were treated with Chinese herbal products (CHPs). Dang-gui-shao-yao-san (Tangkuei and Peony Powder) was the most frequently prescribed formula for treating PD. Conclusion: Primary dysmenorrhea women tended to use Chinese herbal products to deal with painrelated symptoms, rather than use acupuncture. Dang-gui-shao-yao-san, which containing both sedative and anti-inflammatory agents, is the most commonly prescribed Chinese herbal formula for the treatment of PD. A well designed, double-blind, randomized, placebo-controlled study to further evaluate the efficacy of Dang-gui-shao-yao-san as a treatment women with primary dysmenorrhea is warranted. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Dysmenorrhea Chinese herbal product Prevalence Dang-gui-shao-yao-san
1. Introduction Primary dysmenorrhea (PD), defined as the absence of an underlying etiology that is able to explain recurrent, crampy, low abdominal pain that occurs prior to or/and during menses, is one of the most difficult and perplexing health problems of women (Coco, 1999; French, 2005). Primary dysmenorrhea has a major effect on health-related quality of life and productivity as well being both an important aspect of health care expenditure and one of the most common reason for absence from work and school (Grandi et al., 2013). Although several studies have suggested that painkillers are effective way of relieving a sudden attack of menstrual cramps (Nasir and Bope, 2004; Proctor and Farquhar, 2006), in the absence of underlying pathology, no established curable gynecological treatment is available. Thus menstrual leave n Corresponding author at: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Road, Taipei 112, Taiwan. Tel.: þ 886 2 2826 7396. E-mail address: [email protected] (J.-N. Lai).
0378-8741/$ - see front matter & 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2014.01.002
is likely to remain problematic, not only because of personal suffering, but also because it is associated with significant economic loss (Grandi et al., 2013). In addition, the chronic administration of painkillers unfortunately can result in a number of common side-effects such as nausea or an upset stomach; such circumstances drive patients to seek alternative medical advice (Zahradnik et al., 2010). Not surprisingly, alternative therapies have become increasingly popular and are quickly approaching conventional therapy in their frequency of use as a treatment for symptom relief among women with PD (Dawood, 2006). Unfortunately, information is limited regarding the patterns of use of classical traditional Chinese medicine (TCM) in relation to primary dysmenorrhea, which seems to be an area in which complementary and alternative medicine has recently grown in popularity. Furthermore, TCM now seems to offer an important alternative or complement to conventional health care in many Western countries (Zhou and Qu, 2009). In view of the above and because there is a lack of knowledge about what the TCM prescription profile consists of, there is a lack of direction among researchers and doctors trained in conventional medicine when, because of a need
J.-C. Pan et al. / Journal of Ethnopharmacology 152 (2014) 314–319
to target primary dysmenorrhea, they want to explore the potential possibilities of TCM therapy, they want to assess the costeffectiveness of using TCM therapy, and they want to observe the interaction between Chinese herbs and conventional therapies. TCM, which includes acupuncture, traumatology manipulative therapies and Chinese herbal products, has been an important part of health care in Taiwan for hundreds of years and is fully reimbursed under the current National Health Insurance (NHI) system. Accordingly, the claims database provides a platform for understanding the utilization of TCM therapies by licensed TCM doctors (Chen et al., 2007; Lee et al., 2010). The aim of our study is to analyze a random sample of this comprehensive database and to determine the TCM utilization patterns of women with newly diagnosed primary dysmenorrhea in Taiwan. The results of this study should provide valuable information that will enable physicians to respond in an informed way to their patients0 use of TCM, which in turn will further strengthen the patient-physician relationship when treating primary dysmenorrhea.
2. Materials and methods
One million random sample of NHIRD, N = 1,000,000 Exclusion of 500,668 male patients and 145 patients with missing data on gender Having at least three outpatient visits with dysmenorrhea diagnosis within 1 year, N = 49,187
All Patients, N=42,337
Cases of Dysmenorrhea, N=41,960 Exclusion of 10,058 patients with ICD-9-CM code: 614.9, Pelvic inflammatory disease Cases of Dysmenorrhea, N=31,902 Exclusion of 1,532 patients with ICD-9-CM code: 617.9, Endometriosis Cases of Dysmenorrhea, N=30,370 Exclusion of 551 patients with ICD-9-CM code: 617.1, Chocolate cyst Cases of Dysmenorrhea, N=29,819
Exclusion of 1,641 patients with ICD-9-CM code: 620.2, Ovarian cyst
Cases of Dysmenorrhea, N=28,178 Exclusion of 334 patients with ICD-9-CM code: 621.3, Endometrial hyperplasia Cases of Dysmenorrhea, N=27,844
Exclusion of 11 patients with ICD-9-CM code: 622.4, Cervical stricture
Cases of Dysmenorrhea, N=27,833
Exclusion of 73 cases with ICD-9-CM code: V25.1, Insertion of intrauterine
Cases of Primary Dysmenorrhea,
contraceptive device:
N=27,760 Exclusion of prevalent cases
2.2. Study subjects The selection of study subjects from the random sample of one million individuals was performed as follows (Fig. 1). First, we excluded all male beneficiaries (N ¼500,668) as well as those who had missing information concerning gender (n ¼145). Second, female beneficiaries with dysmenorrhea (N ¼49,187) were included to limit the study sample to patients with painful periods (ICD-9 code 625.3). Third, a diagnosis of dysmenorrhea that are caused by another illness rather than the menstrual cycle were excluded to make sure that all the subjects included were primary dysmenorrhea sufferers (exclusion codes: ICD-9 code 617.9 for endometriosis, N ¼1,532; ICD-9 code 617.1 for endometriosis of the ovary, N ¼551; ICD-9 code 218.9 for myoma uterine, N ¼ 6,850; ICD-9 code 614.6 for pelvic adhesions, N ¼377; ICD-9 code 614.9 for pelvic inflammatory disease, N ¼10,058; ICD-9 code 620.2 for ovarian cyst, N ¼ 1,641; ICD-9 code 621.3 for endometrial hyperplasia, N¼334; ICD-9 code 622.4 for cervical stricture, N¼ 11; ICD-9 code V25.1 for insertion or removal of an intrauterine contraceptive device, N¼73). Fourth, the prevalent cases of dysmenorrhea (N¼ 4,419) that had been diagnosed before the end of 2002 and
Exclusion of 6,850 patients with ICD-9-CM code: 218.9, Myoma uterine Exclusion of 377 patients with ICD-9-CM code:614.6, Pelvic adhesions
2.1. Data resources This study was designed as a cross sectional survey analyzing a sample of one million subjects selected at random from the 22 million beneficiaries of the National Health Insurance scheme of Taiwan. The aim was to determine the prevalence of using prescribed Chinese herbal products among PD women between January 1, 2003, and December 31, 2008. All data were obtained from the National Health Insurance Research Database (NHIRD), which includes all the reimbursement data of the NHI with the identification numbers of all individuals encrypted and transformed; this database is maintained by the National Health Research Institutes of Taiwan (N.H.R.I.). The NHIRD database contained patient0 s gender and date of birth, all records of clinical visits and hospitalization, all drugs prescribed and their dosages, including CHP, and three major diagnoses coded in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) format (C.f.D.C.a.P.). Since this study employed de-identified secondary data, it was exempt from full review by the Taipei City Hospital Institutional Review Board.
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of dysmenorrhea before the end of 2002, N=4,419 Cases of Primary Dysmenorrhea during 2003~2008, N=23,341
Exclusion of cases where the patient is age >50 Cases of Primary Dysmenorrhea during 2003~2008, N=23,125 Exclusion of cases where the patient has insurance data missing Cases of Primary Dysmenorrhea during 2003~2008, N=23,118
Fig. 1. Flow chart for identifying the outpatient ICD-9-CM code: 625.3 for dysmenorrhea from the National Health Insurance Research Database (NHIRD) of Taiwan over the study period 2003 to 2008.
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the cases that lacked complete NHI reimbursement data (n¼ 7) were also excluded to make sure that all the subjects included were newly diagnosed with primary dysmenorrhea. Fifth, subjects over the age of 50 years (N¼216) were excluded to limit the study sample to the women of reproductive age in Taiwan. Finally, a total of 23,118 study subjects were included in the study. 2.3. Study variables To determine the key independent variables for utilization of CHPs among PD women, series of demographic factors based on previous studies were selected (Latthe et al., 2006; Chang et al., 2008). Women suffering from PD were classified, based on age, into one of four groups, as follows: r20 years, 21–30 years, 31–40 years, and 41–50 years. The geographic areas of Taiwan in which the women suffering from PD resided were classified into the following seven regions: Taipei city, Kaohsiung city, Northern region, Central region, Southern region, Eastern region and Outlying islands. The patients0 monthly income in New Taiwan Dollars (NT$) was categorized as one of the following into four levels: $0, $1–$19,999, $20,000–$39,999, and Z$40,000. 2.4. Statistical analysis Data analysis consisted of descriptive statistics, including the prescription rates of the CHP users stratified by patient0 s demographic characteristics, indications for the prescription of CHPs, and the most frequently prescribed herbal formulae for treating dysmenorrhea. The indications were coded according to the ICD-9-CM, and grouped into different broader disease categories. The ICD-9-CM codes 460–519 were classified as diseases of the respiratory system. Codes 780–799 were grouped as symptoms, signs, and ill-defined conditions, and codes 520–579 were classified as diseases of the digestive system. The potential effects of the Chinese herbs contained in ten most commonly prescribed CHPs were grouped according to previous in vivo and in vitro studies and these are summarized in Table 4 (Wieser et al., 2007). Multiple logistic regression was conducted to evaluate the factors that correlated with CHP use. A significance level of α ¼0.05 was selected. The statistical software SAS 9.13 was used for data management and analysis.
3. Results The database of outpatient claims contained information on 23,118 women with primary dysmenorrhea during the years 2003–2008. Among them, 12,349 (53.4%) PD women sought care from a TCM practitioner. Details on the demographic distribution of the TCM users and non-users are provided in Table 1. The women suffering from PD who did not use CHPs were slight older than the TCM users. More TCM users had no income, resided in Central Taiwan, and used non-steroid anti-inflammatory drugs than women suffering from PD who did not use CHP. The adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) obtained by multiple logistic regression are shown in Table 1. Compared with the age group 21–30 years (aOR¼1.00), those aged 41 years and above were more likely to be non-TCM users. As compared with low income women (aOR¼1.00), women with a higher income level were more likely to be non-TCM users except those whose income level was NT$ Z40,000. As compared with PD women who took any type of non-steroid anti-inflammatory drug (aOR¼1.00), PD women who did not take pain medicine (aOR¼35.75, 95% CI:33.20–38.49) for relieving their dysmenorrhearelated symptoms were more likely to be TCM users. Of the women suffering from PD who visited TCM doctors, 260,190 (99.2%) of the visits involved the prescription of a Chinese
Table 1 Demographic characteristics and the results of multiple logistic regression showing the adjusted odds ratios (aORs) and 95% CIs (confidence intervals) for women in Taiwan with primary dysmenorrhea from 2003 to 2008. Characteristics
TCMa non-user (%)
TCM user (%)
No. of cases
10,769 (46.6)
12,349 (53.4)
aORb(95% CIc)
Age at diagnosis (years) Mean 7 SD 26.17 9.4 o 20 3,537 (32.8) 21-30 4,259 (39.6) 31–40 1,836 (17.1) 41–50 1,137 (10.5)
25.0 7 8.8 4,459 (36.1) 4,872 (39.5) 2,157 (17.5) 861 (6.9)
1.02 (0.94–1.10) 1.00 1.02 (0.94–1.10) 0.67 (0.60–0.74)
Insured salaries (NT$d/month) 0þ 4,551 (42.3) 1–19,999 2,532 (23.5) 20,000–39,999 2,874 (26.7) 440000 812 (7.5)
5,787 (46.9) 2,685 (21.7) 2,832 (22.9) 1,045 (8.5)
1.00 0.88 (0.81–0.96) 0.82 (0.76–0.89) 0.97 (0.86–1.10)
Insured region Taipei city Kaohsiung city Northern Taiwan Central Taiwan Southern Taiwan East Taiwan Outlying islands
2,555 (20.7) 800 (6.5) 3,154 (25.5) 2,836 (23.0) 2,741 (22.2) 213 (1.7) 50 (0.4)
1.00 0.86 (0.77–0.97) 0.75 (0.70–0.81) 1.20 (1.11–1.31) 0.99 (0.91–1.08) 0.66 (0.54–0.80) 0.49 (0.34–0.70)
10,471 (84.8) 1,878 (15.2)
35.75 (33.20–38.49) 1.00
2,066 (19.2) 753 (7.0) 3,396 (31.5) 1,913 (17.8) 2,298 (21.3) 257 (2.4) 86 (0.8)
Painkiller treatment No treatment 1,453 (13.5) NSAID 9,316 (86.5) a
TCM refers to traditional Chinese medicine. OR refers to odds ratio. CI refers to confidence interval. d NT$ refers to new Taiwan dollars. b c
herbal remedy, while the rest involved the prescription of acupuncture or traumatology manipulative therapy. Analysis of the major disease categories for all TCM visits are summarized in Table 2, which shows that “dysmenorrhea” was by far the most common reason for using CHPs (81.9%, N ¼ 212,985), followed by “diseases of the respiratory system” (4.3%, N ¼11,203), and “diseases of the digestive system” (4.0%, N ¼10,574). Details of the most frequently prescribed CHPs for treating dysmenorrhea and its related symptoms by TCM doctors are provided in Table 3, which demonstrates that Dang-gui-shaoyao-san (Tangkuei and Peony Powder) was the most frequently prescribed CHP. This was followed by Jia-wei-xiao-yao-san (Augmented Rambling Powder) and Wen-jing-tang (Tangkuei and Evodia Combination). The ten most frequently prescribed CHPs all consist of Chinese herbs that are historically used to relieve dysmenorrhea-related symptoms. The potential effects of the Chinese herbs used to treat dysmenorrhea and its related symptoms are summarized in Table 4 and include anti-inflammatory, anti-proliferative and pain-alleviating properties.
4. Discussion According to our review of the literature, this study is the first to use a large-scale cross sectional survey to document the prescription of CHPs to primary dysmenorrhea sufferers in Taiwan. We observed that nearly half of women suffering from PD relied on prescription painkillers for the relief of painful periods in Taiwan, as is shown in Table 1. Both physicians and women suffering from PD should be aware of the association between the painkiller use and potential harm. The possibility of recall or selection bias in this study can be excluded because we included patients who were newly diagnosed with primary dysmenorrhea by qualified conventional physicians during the years 2003–2008 from a random sample
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Table 2 Frequency distribution of traditional Chinese medicine (TCM) visits by major disease categories (according to 9th ICD codes) among women in Taiwan with primary dysmenorrhea from 2003 to 2008. Major disease category
ICD-9-CM code range
Infectious and parasitic diseases Neoplasms Endocrine, nutritional and metabolic diseases, and immunity disorders Mental disorders Diseases of the nervous system and sense organs Diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system Diseases of the genitourinary system Dysmenorrhea Other diseases Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Symptoms, signs, and ill-defined conditions Injury and poisoning Supplementary classification Othersn Total n
001–139 140–239 240–279 290–319 320–389 390–459 460–519 520–579 580–629 625.3 680–709 710–739 780–799 800–999 V01-V82
Treatment days (people) Chinese herbal remedies
Acupuncture or traumatology
Total of TCM
129 91 1,025 575 2,140 809 11,203 10,574 219,699 212,985 6,714 5,504 1,630 5,099 147 0 1,565 260,190
0 0 0 0 0 28 394 63 299 264 35 14 421 443 306 0 0 1,968
129 91 1,025 575 2,140 837 11,597 10,637 219,998 213,249 6,749 5,518 2,051 5,542 453 0 1,565 262,158
(7) (4) (16) (17) (71) (23) (367) (336) (11,586) (11,383) (330) (208) (68) (282) (16) (0) (24) (12,270)
(0) (0) (0) (0) (0) (1) (8) (2) (57) (53) (4) (1) (35) (15) (42) (0) (0) (157)
(7) (4) (16) (17) (71) (23) (372) (337) (11,619) (11,414) (333) (209) (102) (294) (57) (0) (24) (12,349)
Include ranges of 280–289, 630–677, 740–759, 760–779 ICD-9-CM code and missing data.
Table 3 Ten most common herbal formulae prescribed by TCM doctors for treatment of dysmenorrhea-related symptoms among women with Primary Dysmenorrhea from 2003 to 2008 in Taiwan. Herbal formulae
English name
Number of person
Average duration of prescription (days)
Dang-gui-shao-yao-san
Tangkuei and Peony Powder Augmented Rambling Powder Tangkuei and Evodia Combination Cinnamon Twig and Poria Pill Fennel Seed and Corydalis Combination Peony and Licorice Combination Four Agents Combination Rambling Powder Engendering Transformation Combination Ginseng and Longan Combination
3,889
51
3,330
51
3,054
48
2,720
38
2,554
33
1,396
15
799
10
767 723
10 7
705
8
Jia-wei-xiao-yao-san Wen-jing-tang Gui-zhi-fu-ling-wan Shao-fu-zhu-yu-tang Shao-yao-gan-cao-tang Si-wu-tang Xiao-yao-san Sheng-hua-tang
Qui-pi-tang
of the population-based NHI database, which has consistently maintained an insurance rate above 96% since 1997. The prevalence of primary dysmenorrhea in Taiwan over the six years in the study was approximately 10% of women of reproductive age; these individuals in Taiwan were experiencing painful periods in the absence of identifiable pelvic pathology; this appears to be low compared with the estimates given by previous surveys (Chan et al., 2009; Chia et al., 2013). The difference in results between the present study and those previously reported is probably due to disparities in definition of primary dysmenorrhea between patients and qualified physicians. Previous studies (Chan et al., 2009; Chia et al., 2013) collected information on primary dysmenorrhea via self-reported questionnaires, which represents the patients0 own perception and
did not rule out the possible presence of an underlying identifiable disease. In contrast to this situation, the perspective of qualified physicians concerning the treatment of menstrual pain relief must be in line with the results of a differential diagnosis. Another possible explanation is that the present study only included women who were suffering from intolerable menstrual cramps and felt the need to seek medical help; individuals who purchased the painkillers over-the-counter thus were not included in the present study. Although the present findings cannot be generalized to a comprehensive analysis of the usage of various types of CAM, the present study reveals the prevalence of TCM use for the treatment of primary dysmenorrhea as prescribed by licensed TCM doctors. The strength of the present study is that it is able to uncover the specific medical disparity between conventional medicine and traditional Chinese medicine in terms of the health seeking behavior of the study subjects. The customer-oriented design of the NHI system of Taiwan is one that includes completely free choice of provider between conventional medical system and the traditional Chinese medical system. As a result, this might potentially result in an increased prevalence of doctor shopping behavior; nevertheless the present study shows that more than 84% of TCM users who were newly diagnosed with primary dysmenorrhea did not have the intention to use painkillers for the relief of their menstrual cramps during the 6-year study period. Furthermore, women suffering from PD who did not take any type of pain medications were more likely to seek advice from a TCM doctor. Hence, we can infer that CHPs for women with primary dysmenorrhea in Taiwan are generally used as replacements for pain relief treatment, rather than as an adjunct to conventional medical treatment. The present findings show that, among women with primary dysmenorrhea, those who are aged 21–30 years or who have a lower income are more likely to be TCM users than other age groups or higher income groups (Table 1). Although, previous studies reported that acupuncture might be an effective treatment for dysmenorrhea, the present study found that, among women experiencing dysmenorrhea, primary dysmenorrhea was the most frequent disease category for all TCM visits and that 499% of treatment involved CHPs (Table 2). Dang-gui-shao-yao-san (Tangkuei and Peony Powder) was the most frequently prescribed formula for treating primary dysmenorrhea in Taiwan (Table 3). Dang-gui-shao-yao-san has
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Table 4 Potential effects of the herbs contained in the ten most common herbal formulae prescribed by TCM doctors for treating dysmenorrhea-related symptoms. Herbal formulae Dang-gui-shao-yao-san
Number of herbs 6
Jia-wei-xiao-yao-san
10
Wen-jing-tang
12
Gui-zhi-fu-ling-wan Shao-fu-zhu-yu-tang
5 10
Shao-yao-gan-cao-tang Si-wu-tang Xiao-yao-san
2 4 8
Sheng-hua-tang
5
Qui-pi-tang
12
Ingredient herbs Alismatis Rhizoma, Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Ligusticum Rhizoma, Paeoniae Alba Radixd, Poriaabd Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Bupleuri Radixad, Poriaabd, Gardeniae Fructus, Glycyrrhizae Radixabd, Menthae Herba, Moutan Cortex, Paeoniae Alba Radixd, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Asini Gelatinum, Evodiae Fructus, Cinnamomi Ramulusbd, Ginseng Radix, Glycyrrhizae Radixabd, Ligusticum Rhizoma, Moutan Cortex, Ophiopogonis Radix, Paeoniae Alba Radixd, Pinellia Tuber, Zingiberis Rhizoma Cinnamomi Ramulusbd, Moutan Cortex, Paeoniae Rubra Radixc, Persicae Semend, Poriaabd Angelicae Sinensis Radixabcd, Cinnamomi Cortex, Corydalis Tuberbd, Foeniculi Fructus, Ligusticum Rhizoma, Myrrhabcd, Paeoniae Rubra Radixc, Trogopterori Faeces, Typhae Pollend, Zingiberis Rhizoma Glycyrrhizae Radixabd, Paeoniae Alba Radixd Angelicae Sinensis Radixabcd, Ligusticum Rhizoma, Paoniae Alba Radixd, Rehmannia Rhizoma Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Bupleuri Radixad, Poriaabd, Glycyrrhizae Radixabcd, Menthae Herba, Paeoniae Alba Radixd, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Glycyrrhizae Radixabd, Ligusticum Rhizoma, Persicae Semend, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Astragali Radix, Atractylodis Ovatae Rhizoma, Ginseng Radix, Poriaabd, Glycyrrhizae Radixabd, Longan Arillus, Polygalae Radix, Vladimiria Radix, Zingiberis Rhizoma, Zizyphi Spinosi Semen, Zizyphus Fructus
a
Antiproliferative effect. Sedative effect. Antioxidant effect. d Anti-inflammatory effect. b c
a long history of use as part of the traditional Chinese pharmacopoeia and was first documented in the classical Chinese text Jin Gui Yao Lue (Essential Prescriptions from the Golden Cabinet) circa 210 A.D. by Zhong-Jing Zhang. In the classical literature Dang-gui-shao-yao-san is said to act as a tonic for the blood and qi and, in addition, to affect water metabolism, which will eventually reduce the severity of abdominal cramps. Among the remaining nine most frequently prescribed formulae for treating primary dysmenorrhea, Shao-fu-zhu-yu-tang (Fennel Seed and Corydalis Combination), Wen-jing-tang (Tangkuei and Evodia Combination), and Gui-zhi-fu-ling-wan (Cinnamon Twig and Poria Pill) are said to reduce blood stasis in the lower abdomen and are very often prescribed by TCM doctors when there is a diagnosis of blood stagnation syndrome due to cold. Other commonly prescribed formulae are associated with relieving pelvic pain (Jia-wei-xiao-yao-san or Augmented Rambling Powder; Sheng-hua-tang or Engendering Transformation Combination, and Shao-yao-gan-cao-tang or Peony and Licorice Combination), with an irregular menstruation cycle (Si-wu-tang or Four Agents Combination and Qui-pi-tang or Ginseng and Longan Combination), or with breast swelling and tenderness (Xiao-yao-san or Tangkuei and Bupleurum Formula). It is apparent from this study that TCM doctors in Taiwan prescribed herbal therapies mainly to reduce menstrual-related pain conditions. Previous studies have revealed that some Chinese herbs have sedative and pain-alleviating properties that act via cytokine suppression and COX-2 inhibition, as shown in Table 4 (Wieser et al., 2007; Zhou and Qu, 2009). However, there is as yet insufficient evidence to allow a conclusion to be reached regarding the cost-effectiveness of the aforementioned formulae in relation to the provision of pain relief among a population suffering from menstrual cramps. Further studies are warranted to assess the formulae generally used by TCM practitioners in this study and to determine whether they are a potential alternative for young adults with menstrual-related pain conditions who do not experience untoward side effects or have long-term morbidities caused by painkiller treatment. The present study has three limitations. First, this study did not include Chinese herbal remedies purchased directly from TCM herbal pharmacies. Thus, the frequency of CHP utilization might have been underestimated. However, because the NHI system has
a comprehensive coverage for TCM prescriptions, which is generally less costly than buying the herbs sold in Taiwan0 s markets, the likelihood is that subjects purchased large quantities of other herbs outside the NHI database is not high. Second, we are unable to draw any conclusion about the relationship between the severity of the menstrual-related pain conditions and TCM utilization for lack of actual clinical data. Lastly, our study is retrospective in nature and also lacks a randomized placebo group. Such limitation means that great caution is necessary in interpreting the results in relation to the effectiveness of the most commonly prescribed Chinese formulae identified in present study due to the high likelihood of a placebo effect.
5. Conclusions Women suffering from primary dysmenorrhea tended to use Chinese herbal products to deal with their pain-related symptoms, rather than use acupuncture. Dang-gui-shao-yao-san is the most frequent formula prescribed by TCM doctors in Taiwan for treating menstrual cramps. Although some evidence does support the use TCM to treat primary dysmenorrhea, the results from the current study could have been confounded by the placebo effect, which emphasizes the need for well conducted, double-blind, randomized, placebocontrolled studies that further evaluate the efficacy of Dang-guishao-yao-san and other formulae when they are used to treat women with primary dysmenorrhea.
Acknowledgments This research was conducted at the Institute of Traditional Medicine at the School of Medicine, National Yang-Ming University, Taipei. The authors would like to express sincere gratitude for the partial support provided for this project in the form of grants from the Department of Health, Taipei City Government (10101-62-012), the Committee on Chinese Medicine and Pharmacy (CCMP100-RD033) and the National Science Council (NSC99-2320-B-010-011MY2), Taiwan.
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References Chan, S.S., et al., 2009. Menstrual problems and health-seeking behaviour in Hong Kong Chinese girls. Hong Kong Med. J. 15 (1), 18–23. Chang, L.-C., et al., 2008. Utilization patterns of Chinese medicine and Western medicine under the National Health Insurance Program in Taiwan, a population-based study from 1997 to 2003. BMC Health Serv. Res. 8 (1), 170. Chen, F.-P., et al., 2007. Use frequency of traditional Chinese medicine in Taiwan. BMC Health Serv. Res. 7 (1), 26. Chia, C.F., et al., 2013. Dysmenorrhoea among Hong Kong university students: prevalence, impact, and management. Hong Kong Med. J. 19 (3), 222–228. Coco, A.S., 1999. Primary dysmenorrhea. Am Fam. Physician 60 (2), 489–496. C.f.D.C.a.P., International Classification of Diseases, Ninth Revision (ICD-9). Available from: 〈http://www.cdc.gov/nchs/icd/icd9.htm〉. Dawood, M.Y., 2006. Primary dysmenorrhea: advances in pathogenesis and management. Obstet. Gynecol. 108 (2), 428–441. French, L., 2005. Dysmenorrhea. Am Fam. Physician 71 (2), 285–291. Grandi, G., et al., 2013. Intermenstrual pelvic pain, quality of life and mood. Gynecol. Obstet. Invest. 75 (2), 97–100.
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Latthe, P., et al., 2006. Factors predisposing women to chronic pelvic pain: systematic review. Br. Med. J. 332 (7544), 749–755. Lee, Y.-C., et al., 2010. The impact of universal National Health Insurance on population health: the experience of Taiwan. BMC Health Serv. Res. 10 (1), 225. N.H.R.I., National Health Insurance Research Database. Available from: 〈http:// www.nhri.org.tw/nhird/date_01.html#_edn1〉. Nasir, L., Bope, E.T., 2004. Management of pelvic pain from dysmenorrhea or endometriosis. J. Am. Board Fam. Pract. 17 (suppl. 1), S43–S47. Proctor, M., Farquhar, C., 2006. Diagnosis and management of dysmenorrhoea. Br. Med. J. 332 (7550), 1134–1138. Wieser, F., et al., 2007. Evolution of medical treatment for endometriosis: back to the roots? Hum. Reproduct. Update 13 (5), 487–499. Zahradnik, H.-P., et al., 2010. Nonsteroidal anti-inflammatory drugs and hormonal contraceptives for pain relief from dysmenorrhea: a review. Contraception 81 (3), 185–196. Zhou, J., Qu, F., 2009. Treating gynaecological disorders with traditional Chinese medicine: a review. Afr. J. Tradit. Complement Altern. Med. 6 (4), 494–517.
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Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep
Research Paper
The traditional Chinese medicine prescription pattern of patients with primary dysmenorrhea in Taiwan: A large-scale cross sectional survey Jung-Chuan Pan a, Yueh-Ting Tsai a, Jung-Nien Lai a,b,n, Ruei-Chi Fang c, Chia-Hao Yeh b a
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei 111, Taiwan c Department of Pharmacy, China Medical University Hospital, Taichung 404, Taiwan b
art ic l e i nf o
a b s t r a c t
Article history: Received 19 November 2013 Received in revised form 31 December 2013 Accepted 2 January 2014 Available online 10 January 2014
Ethnopharmacological relevance: Traditional Chinese medicine (TCM), when given for symptom relief, has gained widespread popularity among women with primary dysmenorrhea (PD). The aim of this study was to analyze the utilization of TCM among PD women in Taiwan. Methods: The use, service frequency and Chinese herbal products prescribed for PD women were evaluated using a cross sectional survey of 23,118 beneficiaries who were recruited from the National Health Insurance Research Database. The logistic regression method was employed to estimate the odds ratios (ORs) for utilization of TCM. Results: Overall, 53.4% (N ¼12,349) of PD women utilized TCM and 92.2% of them sought TCM with the intention of treating their menstruation-related pain symptoms. PD women who do not take prescription painkillers (aOR ¼35.75, 95% CI:33.20–38.49) were more likely to seek TCM treatment than those who took pain medication (aOR ¼1.00). There were a total of 213,249 TCM visits due to PD, of which more than 99% were treated with Chinese herbal products (CHPs). Dang-gui-shao-yao-san (Tangkuei and Peony Powder) was the most frequently prescribed formula for treating PD. Conclusion: Primary dysmenorrhea women tended to use Chinese herbal products to deal with painrelated symptoms, rather than use acupuncture. Dang-gui-shao-yao-san, which containing both sedative and anti-inflammatory agents, is the most commonly prescribed Chinese herbal formula for the treatment of PD. A well designed, double-blind, randomized, placebo-controlled study to further evaluate the efficacy of Dang-gui-shao-yao-san as a treatment women with primary dysmenorrhea is warranted. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Dysmenorrhea Chinese herbal product Prevalence Dang-gui-shao-yao-san
1. Introduction Primary dysmenorrhea (PD), defined as the absence of an underlying etiology that is able to explain recurrent, crampy, low abdominal pain that occurs prior to or/and during menses, is one of the most difficult and perplexing health problems of women (Coco, 1999; French, 2005). Primary dysmenorrhea has a major effect on health-related quality of life and productivity as well being both an important aspect of health care expenditure and one of the most common reason for absence from work and school (Grandi et al., 2013). Although several studies have suggested that painkillers are effective way of relieving a sudden attack of menstrual cramps (Nasir and Bope, 2004; Proctor and Farquhar, 2006), in the absence of underlying pathology, no established curable gynecological treatment is available. Thus menstrual leave n Corresponding author at: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Road, Taipei 112, Taiwan. Tel.: þ 886 2 2826 7396. E-mail address: [email protected] (J.-N. Lai).
0378-8741/$ - see front matter & 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2014.01.002
is likely to remain problematic, not only because of personal suffering, but also because it is associated with significant economic loss (Grandi et al., 2013). In addition, the chronic administration of painkillers unfortunately can result in a number of common side-effects such as nausea or an upset stomach; such circumstances drive patients to seek alternative medical advice (Zahradnik et al., 2010). Not surprisingly, alternative therapies have become increasingly popular and are quickly approaching conventional therapy in their frequency of use as a treatment for symptom relief among women with PD (Dawood, 2006). Unfortunately, information is limited regarding the patterns of use of classical traditional Chinese medicine (TCM) in relation to primary dysmenorrhea, which seems to be an area in which complementary and alternative medicine has recently grown in popularity. Furthermore, TCM now seems to offer an important alternative or complement to conventional health care in many Western countries (Zhou and Qu, 2009). In view of the above and because there is a lack of knowledge about what the TCM prescription profile consists of, there is a lack of direction among researchers and doctors trained in conventional medicine when, because of a need
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to target primary dysmenorrhea, they want to explore the potential possibilities of TCM therapy, they want to assess the costeffectiveness of using TCM therapy, and they want to observe the interaction between Chinese herbs and conventional therapies. TCM, which includes acupuncture, traumatology manipulative therapies and Chinese herbal products, has been an important part of health care in Taiwan for hundreds of years and is fully reimbursed under the current National Health Insurance (NHI) system. Accordingly, the claims database provides a platform for understanding the utilization of TCM therapies by licensed TCM doctors (Chen et al., 2007; Lee et al., 2010). The aim of our study is to analyze a random sample of this comprehensive database and to determine the TCM utilization patterns of women with newly diagnosed primary dysmenorrhea in Taiwan. The results of this study should provide valuable information that will enable physicians to respond in an informed way to their patients0 use of TCM, which in turn will further strengthen the patient-physician relationship when treating primary dysmenorrhea.
2. Materials and methods
One million random sample of NHIRD, N = 1,000,000 Exclusion of 500,668 male patients and 145 patients with missing data on gender Having at least three outpatient visits with dysmenorrhea diagnosis within 1 year, N = 49,187
All Patients, N=42,337
Cases of Dysmenorrhea, N=41,960 Exclusion of 10,058 patients with ICD-9-CM code: 614.9, Pelvic inflammatory disease Cases of Dysmenorrhea, N=31,902 Exclusion of 1,532 patients with ICD-9-CM code: 617.9, Endometriosis Cases of Dysmenorrhea, N=30,370 Exclusion of 551 patients with ICD-9-CM code: 617.1, Chocolate cyst Cases of Dysmenorrhea, N=29,819
Exclusion of 1,641 patients with ICD-9-CM code: 620.2, Ovarian cyst
Cases of Dysmenorrhea, N=28,178 Exclusion of 334 patients with ICD-9-CM code: 621.3, Endometrial hyperplasia Cases of Dysmenorrhea, N=27,844
Exclusion of 11 patients with ICD-9-CM code: 622.4, Cervical stricture
Cases of Dysmenorrhea, N=27,833
Exclusion of 73 cases with ICD-9-CM code: V25.1, Insertion of intrauterine
Cases of Primary Dysmenorrhea,
contraceptive device:
N=27,760 Exclusion of prevalent cases
2.2. Study subjects The selection of study subjects from the random sample of one million individuals was performed as follows (Fig. 1). First, we excluded all male beneficiaries (N ¼500,668) as well as those who had missing information concerning gender (n ¼145). Second, female beneficiaries with dysmenorrhea (N ¼49,187) were included to limit the study sample to patients with painful periods (ICD-9 code 625.3). Third, a diagnosis of dysmenorrhea that are caused by another illness rather than the menstrual cycle were excluded to make sure that all the subjects included were primary dysmenorrhea sufferers (exclusion codes: ICD-9 code 617.9 for endometriosis, N ¼1,532; ICD-9 code 617.1 for endometriosis of the ovary, N ¼551; ICD-9 code 218.9 for myoma uterine, N ¼ 6,850; ICD-9 code 614.6 for pelvic adhesions, N ¼377; ICD-9 code 614.9 for pelvic inflammatory disease, N ¼10,058; ICD-9 code 620.2 for ovarian cyst, N ¼ 1,641; ICD-9 code 621.3 for endometrial hyperplasia, N¼334; ICD-9 code 622.4 for cervical stricture, N¼ 11; ICD-9 code V25.1 for insertion or removal of an intrauterine contraceptive device, N¼73). Fourth, the prevalent cases of dysmenorrhea (N¼ 4,419) that had been diagnosed before the end of 2002 and
Exclusion of 6,850 patients with ICD-9-CM code: 218.9, Myoma uterine Exclusion of 377 patients with ICD-9-CM code:614.6, Pelvic adhesions
2.1. Data resources This study was designed as a cross sectional survey analyzing a sample of one million subjects selected at random from the 22 million beneficiaries of the National Health Insurance scheme of Taiwan. The aim was to determine the prevalence of using prescribed Chinese herbal products among PD women between January 1, 2003, and December 31, 2008. All data were obtained from the National Health Insurance Research Database (NHIRD), which includes all the reimbursement data of the NHI with the identification numbers of all individuals encrypted and transformed; this database is maintained by the National Health Research Institutes of Taiwan (N.H.R.I.). The NHIRD database contained patient0 s gender and date of birth, all records of clinical visits and hospitalization, all drugs prescribed and their dosages, including CHP, and three major diagnoses coded in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) format (C.f.D.C.a.P.). Since this study employed de-identified secondary data, it was exempt from full review by the Taipei City Hospital Institutional Review Board.
315
of dysmenorrhea before the end of 2002, N=4,419 Cases of Primary Dysmenorrhea during 2003~2008, N=23,341
Exclusion of cases where the patient is age >50 Cases of Primary Dysmenorrhea during 2003~2008, N=23,125 Exclusion of cases where the patient has insurance data missing Cases of Primary Dysmenorrhea during 2003~2008, N=23,118
Fig. 1. Flow chart for identifying the outpatient ICD-9-CM code: 625.3 for dysmenorrhea from the National Health Insurance Research Database (NHIRD) of Taiwan over the study period 2003 to 2008.
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the cases that lacked complete NHI reimbursement data (n¼ 7) were also excluded to make sure that all the subjects included were newly diagnosed with primary dysmenorrhea. Fifth, subjects over the age of 50 years (N¼216) were excluded to limit the study sample to the women of reproductive age in Taiwan. Finally, a total of 23,118 study subjects were included in the study. 2.3. Study variables To determine the key independent variables for utilization of CHPs among PD women, series of demographic factors based on previous studies were selected (Latthe et al., 2006; Chang et al., 2008). Women suffering from PD were classified, based on age, into one of four groups, as follows: r20 years, 21–30 years, 31–40 years, and 41–50 years. The geographic areas of Taiwan in which the women suffering from PD resided were classified into the following seven regions: Taipei city, Kaohsiung city, Northern region, Central region, Southern region, Eastern region and Outlying islands. The patients0 monthly income in New Taiwan Dollars (NT$) was categorized as one of the following into four levels: $0, $1–$19,999, $20,000–$39,999, and Z$40,000. 2.4. Statistical analysis Data analysis consisted of descriptive statistics, including the prescription rates of the CHP users stratified by patient0 s demographic characteristics, indications for the prescription of CHPs, and the most frequently prescribed herbal formulae for treating dysmenorrhea. The indications were coded according to the ICD-9-CM, and grouped into different broader disease categories. The ICD-9-CM codes 460–519 were classified as diseases of the respiratory system. Codes 780–799 were grouped as symptoms, signs, and ill-defined conditions, and codes 520–579 were classified as diseases of the digestive system. The potential effects of the Chinese herbs contained in ten most commonly prescribed CHPs were grouped according to previous in vivo and in vitro studies and these are summarized in Table 4 (Wieser et al., 2007). Multiple logistic regression was conducted to evaluate the factors that correlated with CHP use. A significance level of α ¼0.05 was selected. The statistical software SAS 9.13 was used for data management and analysis.
3. Results The database of outpatient claims contained information on 23,118 women with primary dysmenorrhea during the years 2003–2008. Among them, 12,349 (53.4%) PD women sought care from a TCM practitioner. Details on the demographic distribution of the TCM users and non-users are provided in Table 1. The women suffering from PD who did not use CHPs were slight older than the TCM users. More TCM users had no income, resided in Central Taiwan, and used non-steroid anti-inflammatory drugs than women suffering from PD who did not use CHP. The adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) obtained by multiple logistic regression are shown in Table 1. Compared with the age group 21–30 years (aOR¼1.00), those aged 41 years and above were more likely to be non-TCM users. As compared with low income women (aOR¼1.00), women with a higher income level were more likely to be non-TCM users except those whose income level was NT$ Z40,000. As compared with PD women who took any type of non-steroid anti-inflammatory drug (aOR¼1.00), PD women who did not take pain medicine (aOR¼35.75, 95% CI:33.20–38.49) for relieving their dysmenorrhearelated symptoms were more likely to be TCM users. Of the women suffering from PD who visited TCM doctors, 260,190 (99.2%) of the visits involved the prescription of a Chinese
Table 1 Demographic characteristics and the results of multiple logistic regression showing the adjusted odds ratios (aORs) and 95% CIs (confidence intervals) for women in Taiwan with primary dysmenorrhea from 2003 to 2008. Characteristics
TCMa non-user (%)
TCM user (%)
No. of cases
10,769 (46.6)
12,349 (53.4)
aORb(95% CIc)
Age at diagnosis (years) Mean 7 SD 26.17 9.4 o 20 3,537 (32.8) 21-30 4,259 (39.6) 31–40 1,836 (17.1) 41–50 1,137 (10.5)
25.0 7 8.8 4,459 (36.1) 4,872 (39.5) 2,157 (17.5) 861 (6.9)
1.02 (0.94–1.10) 1.00 1.02 (0.94–1.10) 0.67 (0.60–0.74)
Insured salaries (NT$d/month) 0þ 4,551 (42.3) 1–19,999 2,532 (23.5) 20,000–39,999 2,874 (26.7) 440000 812 (7.5)
5,787 (46.9) 2,685 (21.7) 2,832 (22.9) 1,045 (8.5)
1.00 0.88 (0.81–0.96) 0.82 (0.76–0.89) 0.97 (0.86–1.10)
Insured region Taipei city Kaohsiung city Northern Taiwan Central Taiwan Southern Taiwan East Taiwan Outlying islands
2,555 (20.7) 800 (6.5) 3,154 (25.5) 2,836 (23.0) 2,741 (22.2) 213 (1.7) 50 (0.4)
1.00 0.86 (0.77–0.97) 0.75 (0.70–0.81) 1.20 (1.11–1.31) 0.99 (0.91–1.08) 0.66 (0.54–0.80) 0.49 (0.34–0.70)
10,471 (84.8) 1,878 (15.2)
35.75 (33.20–38.49) 1.00
2,066 (19.2) 753 (7.0) 3,396 (31.5) 1,913 (17.8) 2,298 (21.3) 257 (2.4) 86 (0.8)
Painkiller treatment No treatment 1,453 (13.5) NSAID 9,316 (86.5) a
TCM refers to traditional Chinese medicine. OR refers to odds ratio. CI refers to confidence interval. d NT$ refers to new Taiwan dollars. b c
herbal remedy, while the rest involved the prescription of acupuncture or traumatology manipulative therapy. Analysis of the major disease categories for all TCM visits are summarized in Table 2, which shows that “dysmenorrhea” was by far the most common reason for using CHPs (81.9%, N ¼ 212,985), followed by “diseases of the respiratory system” (4.3%, N ¼11,203), and “diseases of the digestive system” (4.0%, N ¼10,574). Details of the most frequently prescribed CHPs for treating dysmenorrhea and its related symptoms by TCM doctors are provided in Table 3, which demonstrates that Dang-gui-shaoyao-san (Tangkuei and Peony Powder) was the most frequently prescribed CHP. This was followed by Jia-wei-xiao-yao-san (Augmented Rambling Powder) and Wen-jing-tang (Tangkuei and Evodia Combination). The ten most frequently prescribed CHPs all consist of Chinese herbs that are historically used to relieve dysmenorrhea-related symptoms. The potential effects of the Chinese herbs used to treat dysmenorrhea and its related symptoms are summarized in Table 4 and include anti-inflammatory, anti-proliferative and pain-alleviating properties.
4. Discussion According to our review of the literature, this study is the first to use a large-scale cross sectional survey to document the prescription of CHPs to primary dysmenorrhea sufferers in Taiwan. We observed that nearly half of women suffering from PD relied on prescription painkillers for the relief of painful periods in Taiwan, as is shown in Table 1. Both physicians and women suffering from PD should be aware of the association between the painkiller use and potential harm. The possibility of recall or selection bias in this study can be excluded because we included patients who were newly diagnosed with primary dysmenorrhea by qualified conventional physicians during the years 2003–2008 from a random sample
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Table 2 Frequency distribution of traditional Chinese medicine (TCM) visits by major disease categories (according to 9th ICD codes) among women in Taiwan with primary dysmenorrhea from 2003 to 2008. Major disease category
ICD-9-CM code range
Infectious and parasitic diseases Neoplasms Endocrine, nutritional and metabolic diseases, and immunity disorders Mental disorders Diseases of the nervous system and sense organs Diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system Diseases of the genitourinary system Dysmenorrhea Other diseases Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Symptoms, signs, and ill-defined conditions Injury and poisoning Supplementary classification Othersn Total n
001–139 140–239 240–279 290–319 320–389 390–459 460–519 520–579 580–629 625.3 680–709 710–739 780–799 800–999 V01-V82
Treatment days (people) Chinese herbal remedies
Acupuncture or traumatology
Total of TCM
129 91 1,025 575 2,140 809 11,203 10,574 219,699 212,985 6,714 5,504 1,630 5,099 147 0 1,565 260,190
0 0 0 0 0 28 394 63 299 264 35 14 421 443 306 0 0 1,968
129 91 1,025 575 2,140 837 11,597 10,637 219,998 213,249 6,749 5,518 2,051 5,542 453 0 1,565 262,158
(7) (4) (16) (17) (71) (23) (367) (336) (11,586) (11,383) (330) (208) (68) (282) (16) (0) (24) (12,270)
(0) (0) (0) (0) (0) (1) (8) (2) (57) (53) (4) (1) (35) (15) (42) (0) (0) (157)
(7) (4) (16) (17) (71) (23) (372) (337) (11,619) (11,414) (333) (209) (102) (294) (57) (0) (24) (12,349)
Include ranges of 280–289, 630–677, 740–759, 760–779 ICD-9-CM code and missing data.
Table 3 Ten most common herbal formulae prescribed by TCM doctors for treatment of dysmenorrhea-related symptoms among women with Primary Dysmenorrhea from 2003 to 2008 in Taiwan. Herbal formulae
English name
Number of person
Average duration of prescription (days)
Dang-gui-shao-yao-san
Tangkuei and Peony Powder Augmented Rambling Powder Tangkuei and Evodia Combination Cinnamon Twig and Poria Pill Fennel Seed and Corydalis Combination Peony and Licorice Combination Four Agents Combination Rambling Powder Engendering Transformation Combination Ginseng and Longan Combination
3,889
51
3,330
51
3,054
48
2,720
38
2,554
33
1,396
15
799
10
767 723
10 7
705
8
Jia-wei-xiao-yao-san Wen-jing-tang Gui-zhi-fu-ling-wan Shao-fu-zhu-yu-tang Shao-yao-gan-cao-tang Si-wu-tang Xiao-yao-san Sheng-hua-tang
Qui-pi-tang
of the population-based NHI database, which has consistently maintained an insurance rate above 96% since 1997. The prevalence of primary dysmenorrhea in Taiwan over the six years in the study was approximately 10% of women of reproductive age; these individuals in Taiwan were experiencing painful periods in the absence of identifiable pelvic pathology; this appears to be low compared with the estimates given by previous surveys (Chan et al., 2009; Chia et al., 2013). The difference in results between the present study and those previously reported is probably due to disparities in definition of primary dysmenorrhea between patients and qualified physicians. Previous studies (Chan et al., 2009; Chia et al., 2013) collected information on primary dysmenorrhea via self-reported questionnaires, which represents the patients0 own perception and
did not rule out the possible presence of an underlying identifiable disease. In contrast to this situation, the perspective of qualified physicians concerning the treatment of menstrual pain relief must be in line with the results of a differential diagnosis. Another possible explanation is that the present study only included women who were suffering from intolerable menstrual cramps and felt the need to seek medical help; individuals who purchased the painkillers over-the-counter thus were not included in the present study. Although the present findings cannot be generalized to a comprehensive analysis of the usage of various types of CAM, the present study reveals the prevalence of TCM use for the treatment of primary dysmenorrhea as prescribed by licensed TCM doctors. The strength of the present study is that it is able to uncover the specific medical disparity between conventional medicine and traditional Chinese medicine in terms of the health seeking behavior of the study subjects. The customer-oriented design of the NHI system of Taiwan is one that includes completely free choice of provider between conventional medical system and the traditional Chinese medical system. As a result, this might potentially result in an increased prevalence of doctor shopping behavior; nevertheless the present study shows that more than 84% of TCM users who were newly diagnosed with primary dysmenorrhea did not have the intention to use painkillers for the relief of their menstrual cramps during the 6-year study period. Furthermore, women suffering from PD who did not take any type of pain medications were more likely to seek advice from a TCM doctor. Hence, we can infer that CHPs for women with primary dysmenorrhea in Taiwan are generally used as replacements for pain relief treatment, rather than as an adjunct to conventional medical treatment. The present findings show that, among women with primary dysmenorrhea, those who are aged 21–30 years or who have a lower income are more likely to be TCM users than other age groups or higher income groups (Table 1). Although, previous studies reported that acupuncture might be an effective treatment for dysmenorrhea, the present study found that, among women experiencing dysmenorrhea, primary dysmenorrhea was the most frequent disease category for all TCM visits and that 499% of treatment involved CHPs (Table 2). Dang-gui-shao-yao-san (Tangkuei and Peony Powder) was the most frequently prescribed formula for treating primary dysmenorrhea in Taiwan (Table 3). Dang-gui-shao-yao-san has
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Table 4 Potential effects of the herbs contained in the ten most common herbal formulae prescribed by TCM doctors for treating dysmenorrhea-related symptoms. Herbal formulae Dang-gui-shao-yao-san
Number of herbs 6
Jia-wei-xiao-yao-san
10
Wen-jing-tang
12
Gui-zhi-fu-ling-wan Shao-fu-zhu-yu-tang
5 10
Shao-yao-gan-cao-tang Si-wu-tang Xiao-yao-san
2 4 8
Sheng-hua-tang
5
Qui-pi-tang
12
Ingredient herbs Alismatis Rhizoma, Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Ligusticum Rhizoma, Paeoniae Alba Radixd, Poriaabd Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Bupleuri Radixad, Poriaabd, Gardeniae Fructus, Glycyrrhizae Radixabd, Menthae Herba, Moutan Cortex, Paeoniae Alba Radixd, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Asini Gelatinum, Evodiae Fructus, Cinnamomi Ramulusbd, Ginseng Radix, Glycyrrhizae Radixabd, Ligusticum Rhizoma, Moutan Cortex, Ophiopogonis Radix, Paeoniae Alba Radixd, Pinellia Tuber, Zingiberis Rhizoma Cinnamomi Ramulusbd, Moutan Cortex, Paeoniae Rubra Radixc, Persicae Semend, Poriaabd Angelicae Sinensis Radixabcd, Cinnamomi Cortex, Corydalis Tuberbd, Foeniculi Fructus, Ligusticum Rhizoma, Myrrhabcd, Paeoniae Rubra Radixc, Trogopterori Faeces, Typhae Pollend, Zingiberis Rhizoma Glycyrrhizae Radixabd, Paeoniae Alba Radixd Angelicae Sinensis Radixabcd, Ligusticum Rhizoma, Paoniae Alba Radixd, Rehmannia Rhizoma Angelicae Sinensis Radixabcd, Atractylodis Ovatae Rhizoma, Bupleuri Radixad, Poriaabd, Glycyrrhizae Radixabcd, Menthae Herba, Paeoniae Alba Radixd, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Glycyrrhizae Radixabd, Ligusticum Rhizoma, Persicae Semend, Zingiberis Rhizoma Angelicae Sinensis Radixabcd, Astragali Radix, Atractylodis Ovatae Rhizoma, Ginseng Radix, Poriaabd, Glycyrrhizae Radixabd, Longan Arillus, Polygalae Radix, Vladimiria Radix, Zingiberis Rhizoma, Zizyphi Spinosi Semen, Zizyphus Fructus
a
Antiproliferative effect. Sedative effect. Antioxidant effect. d Anti-inflammatory effect. b c
a long history of use as part of the traditional Chinese pharmacopoeia and was first documented in the classical Chinese text Jin Gui Yao Lue (Essential Prescriptions from the Golden Cabinet) circa 210 A.D. by Zhong-Jing Zhang. In the classical literature Dang-gui-shao-yao-san is said to act as a tonic for the blood and qi and, in addition, to affect water metabolism, which will eventually reduce the severity of abdominal cramps. Among the remaining nine most frequently prescribed formulae for treating primary dysmenorrhea, Shao-fu-zhu-yu-tang (Fennel Seed and Corydalis Combination), Wen-jing-tang (Tangkuei and Evodia Combination), and Gui-zhi-fu-ling-wan (Cinnamon Twig and Poria Pill) are said to reduce blood stasis in the lower abdomen and are very often prescribed by TCM doctors when there is a diagnosis of blood stagnation syndrome due to cold. Other commonly prescribed formulae are associated with relieving pelvic pain (Jia-wei-xiao-yao-san or Augmented Rambling Powder; Sheng-hua-tang or Engendering Transformation Combination, and Shao-yao-gan-cao-tang or Peony and Licorice Combination), with an irregular menstruation cycle (Si-wu-tang or Four Agents Combination and Qui-pi-tang or Ginseng and Longan Combination), or with breast swelling and tenderness (Xiao-yao-san or Tangkuei and Bupleurum Formula). It is apparent from this study that TCM doctors in Taiwan prescribed herbal therapies mainly to reduce menstrual-related pain conditions. Previous studies have revealed that some Chinese herbs have sedative and pain-alleviating properties that act via cytokine suppression and COX-2 inhibition, as shown in Table 4 (Wieser et al., 2007; Zhou and Qu, 2009). However, there is as yet insufficient evidence to allow a conclusion to be reached regarding the cost-effectiveness of the aforementioned formulae in relation to the provision of pain relief among a population suffering from menstrual cramps. Further studies are warranted to assess the formulae generally used by TCM practitioners in this study and to determine whether they are a potential alternative for young adults with menstrual-related pain conditions who do not experience untoward side effects or have long-term morbidities caused by painkiller treatment. The present study has three limitations. First, this study did not include Chinese herbal remedies purchased directly from TCM herbal pharmacies. Thus, the frequency of CHP utilization might have been underestimated. However, because the NHI system has
a comprehensive coverage for TCM prescriptions, which is generally less costly than buying the herbs sold in Taiwan0 s markets, the likelihood is that subjects purchased large quantities of other herbs outside the NHI database is not high. Second, we are unable to draw any conclusion about the relationship between the severity of the menstrual-related pain conditions and TCM utilization for lack of actual clinical data. Lastly, our study is retrospective in nature and also lacks a randomized placebo group. Such limitation means that great caution is necessary in interpreting the results in relation to the effectiveness of the most commonly prescribed Chinese formulae identified in present study due to the high likelihood of a placebo effect.
5. Conclusions Women suffering from primary dysmenorrhea tended to use Chinese herbal products to deal with their pain-related symptoms, rather than use acupuncture. Dang-gui-shao-yao-san is the most frequent formula prescribed by TCM doctors in Taiwan for treating menstrual cramps. Although some evidence does support the use TCM to treat primary dysmenorrhea, the results from the current study could have been confounded by the placebo effect, which emphasizes the need for well conducted, double-blind, randomized, placebocontrolled studies that further evaluate the efficacy of Dang-guishao-yao-san and other formulae when they are used to treat women with primary dysmenorrhea.
Acknowledgments This research was conducted at the Institute of Traditional Medicine at the School of Medicine, National Yang-Ming University, Taipei. The authors would like to express sincere gratitude for the partial support provided for this project in the form of grants from the Department of Health, Taipei City Government (10101-62-012), the Committee on Chinese Medicine and Pharmacy (CCMP100-RD033) and the National Science Council (NSC99-2320-B-010-011MY2), Taiwan.
J.-C. Pan et al. / Journal of Ethnopharmacology 152 (2014) 314–319
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