General Use of Chinese Herbal Products among Female Patients with Mastitis in Taiwan

Objectives Little information is available regarding the use of Chinese herbal medicine to treat mastitis. This study evaluated the prescription patterns of Chinese herbal medicine products in women with mastitis in Taiwan. Design This is a population-based cross-sectional study. Setting. 8,531 women aged 20–49 years, who received a diagnosis of mastitis between 2004 and 2013, were identified from the Longitudinal Health Insurance Database in Taiwan. We collected data on demographic characteristics, including age, monthly insurance premium, and urbanization level. The ten most Chinese herbal medicines prescribed for mastitis were assessed, including frequency, percentage, average daily dose, and average duration of prescription. Main outcome measures. We analysed the ten most single Chinese herbs and Chinese herbal formulae prescribed for mastitis. Results Overall, 437 (5.1%) women received Chinese herbal medicine to treat mastitis. Mai Men Dong (Ophiopogon japonicus (Thunb.) Ker Gawl.; 22.3%), Pu Gong Yin (Taraxacum mongolicum Hand.-Mazz.; 7.8%), and Wang Bu Liu Xing (Vaccaria hispanica (Mill.) Rauschert; 3.5%) were three of the most commonly prescribed single Chinese herbs for mastitis. Xian-Fang-Huo-Ming-Yin (18.2%), Jia-Wei-Xiao-Yao-San (9.1%), and Chai-Hu-Shu-Gan-San (8.4%) were three of the most commonly prescribed Chinese herbal formulae. Conclusion Xian-Fang-Huo-Ming-Yin can clear heat, detoxify body, alleviate swelling, activate blood, and relieve pain. It was the most frequently prescribed Chinese herbal formula in patients with mastitis.


Introduction
Mastitis is an inflammation of the breast, which may or may not involve an infection. It is usually related to lactation. e World Health Organization reported that incidence of mastitis in lactating women ranged from 3% to 33% [1]; it usually occurs in the first six weeks postpartum, and the incidence gradually declines thereafter [2]. e major causes of mastitis are milk stasis and infection [1]; other factors tenderness (98%), malaise (87%), fever (82%), chills (78%), redness (78%), and a hot spot on the affected breast (62%).
Mastitis should be treated immediately, as a delay in treatment or inappropriate management can lead to breast abscess, which occurs in 5 to 11% of mastitis cases [6]. e treatments for mastitis usually include effective milk removal, counselling, as well as antibiotic and symptomatic treatment. Other therapies include the use of cabbage leaves and herbal treatment [1]. Cabbage leaves, with both antibiotic and anti-irritant properties, can reduce pain and increase breastfeeding duration [1,7]. Gleditsiae Fructus extract has also been reported to be effective in treating mastitis [1]. Wu et al. [8] found that Taraxaci Herba, Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Alba, and Citri Reticulatae Semen were the most commonly prescribed Chinese medicines for mastitis.
Mastitis and breast abscess are known as "Ru Yong" (breast carbuncle) in Chinese medicine. Ge Zhi Yu Lun, an ancient Chinese medical text, states that the breasts itself belong to the stomach meridian, and the nipples belong to the liver meridian. If a nursing mother is angry, depressed, or eats excessive amounts of greasy food, the Qi will stagnate and milk ducts will become blocked, causing milk stasis, which may transform into heat and possibly also an abscess. If the infant has interior heat, they might pass the heat to the mother through breastfeeding, which can cause breast lumps [9]. Chinese medicine is widely used in Taiwan. However, very few studies have investigated the application of Chinese herbal medicine (CHM) in the treatment of mastitis. erefore, the aim of the study is to assess the patterns of CHM prescriptions to treat mastitis in women in Taiwan from the Longitudinal Health Insurance Database (LHID).

Data Source and Study Population.
is retrospective, population-based, cross-sectional study used data from the Longitudinal Health Insurance Database (LHID), where one million beneficiaries were randomly selected from the National Health Insurance Research Database (NHIRD) in Taiwan. e LHID sample and all NHIRD enrollees had no differences in age, gender, or average insured payroll-related premiums. e LHID database contains information about outpatient visits, hospital admissions, prescriptions, disease status, and patient demographics. To protect confidentiality, all identification numbers of patients and medical institutions were encrypted and maintained by Taiwan's National Health Research Institutes before extracting and analysing data. e diagnostic codes used in the LHID were according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) coding. In addition, this study was approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB No. CE15069A-3, Taiwan), and the requirement for informed consent was waived.
A sample of one million patients was randomly selected from the National Health Insurance Research Database (NHIRD). All patients without mastitis (ICD-9-CM code 611.0) were excluded (n � 989,359). A total of 10,641 women who received a diagnosis of mastitis (ICD-9-CM code 611.0) between 2004 and 2013 were identified. We excluded patients aged <20 or ≥50 years of age (n � 1,900) and those who were diagnosed with mastitis before 2004 (n � 210). e date of the initial mastitis diagnosis was defined as the index date. e final sample included 8,531 newly diagnosed patients with mastitis who were classified into those who did and did not use CHM to treat mastitis. Figure 1 shows a flow diagram of the study selection process.

Chinese Herbal Medicine Use.
e primary variable of interest was whether patients received CHM treatment for mastitis (ICD-9-CM code 611.0). Chinese herbal medicine products are prescribed for outpatient treatment by traditional Chinese medicine (TCM) physicians according to Taiwan's National Health Insurance program guidelines. Chinese herbal medicine use was defined as patients who had been prescribed CHM for treating mastitis at least once after the index date, whereas non-CHM use was defined as those who did not visit TCM physicians. e possible pharmacological effects of single Chinese herbs were searched from scientific literature published between July 2006 and January 2019, and the retrieval database is PubMed.

Variables.
e demographic variables compared between the CHM and non-CHM groups were age at mastitis diagnosis, monthly insurance premium, and urbanization level.
Age was classified into groups of 20−29, 30−39, and 40−49. Individual monthly insurance premium was determined according to work salary, and premiums (in Taiwan dollars (TWD)) were classified into ≥45,801, 28,801-45,800, 15,841-28,800, <15,840, and dependent groups. e dependent group included students, stay-at-home parents, and family members without a fixed salary. e urbanization level was classified as urban, suburban, and rural.

Statistical
Analyses. Distribution of the characteristics between patients with mastitis, with and without CHM, was examined using chi-square or Fisher's exact tests for categorical variables and Student's t-test for continuous variables. e prescription patterns of the 10 most prescribed single Chinese herbs and Chinese herbal formulae for mastitis treatment were analysed, including frequencies, percentages, average use duration (days/visit), and average daily dose (g). e threshold for statistical significance was set at p < 0.05. All analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).

Results
We included 8,531 women who were newly diagnosed with mastitis between 2004 and 2013. Of these, 437 (5.1%) were CHM users and 8,094 (94.8%) were non-CHM users. e demographic characteristics of CHM users and nonusers are shown in Table 1. e mean age at diagnosis was 33.3 and 2 Evidence-Based Complementary and Alternative Medicine 32.9 years in CHM and non-CHM users, respectively. e monthly insurance premium results revealed that over 60% of participants belong to the dependent group, which included students, stay-at-home parents, and those without a fixed salary. ere was no difference in the urbanization level between the two groups. e prescription patterns of CHM and the 10 most prescribed single Chinese herbs and Chinese herbal formulae for mastitis are presented in Tables 2 and 3 were not only part of the ten most single Chinese herbs prescribed for mastitis but also part of the ingredients of the ten most formulae prescribed for mastitis. e Chinese herbal medicine effects are summarized in Tables 2 and 3; most of these Chinese herbs can clear heat, resolve toxin, reduce swelling, and relieve pain. e possible

Discussion
Mastitis is a common problem faced by breastfeeding women. However, this is the first study to investigate TCM prescription patterns among female patients with mastitis in Taiwan. For this, we used data from the LHID on   [20]. In TCM, "Ru Yong" is caused by liver Qi depression, stomach heat, infections, inadequate breastfeeding, or Qi counterflow during pregnancy, which can lead to milk accumulation. In the initial stage of treatment, the aim is to relieve symptoms, mainly by soothing the liver and regulating Qi, clearing stomach fire, dispersing nodules, and letting the milk flow. If mastitis progresses to an abscess, the aim is to expel pus and toxins. e three most prescribed Chinese herbal formulae were Xian-Fang-Huo-Ming-Yin (18.2%), Jia-Wei-Xiao-Yao-San (9.1%), and Chai-Hu-Shu-Gan-San (8.4%). e three most prescribed Chinese herbs were Mai Men Dong (22.3%), Pu Gong Yin (7.8%), and Wang Bu Liu Xing (3.5%).
Xian-Fang-Huo-Ming-Yin is a well-known Chinese herbal formula that can clear heat, detoxify body, alleviate swelling, activate blood flow, and relieve pain. It has been widely applied to treat sores, carbuncles, and abscesses. Although it is commonly prescribed for mastitis, no research has yet documented the effect of Xian-Fang-Huo-Ming-Yin on mastitis.
ough it can stimulate lactation, disperse swelling, and expel pus, excessive hunting has led to becoming endangered. In 2000, the Department of Health in Taiwan banned the use of products obtained from protected species (e.g., pangolin, bear bile, musk, and Saiga antelope horn) from medical use [23]. e committee on Chinese Medicine and Pharmacy revealed that Wang Bu Liu Xing could replace Chuan Shan Jia to help increase lactation [24]. e Dean of the American College of Traditional Chinese Medicine, Steve Given, mentioned that there are 125 alternatives for Chuan Shan Jia, depending on the diagnosis, since alternatives of TCM could be composed of various products instead of a oneto-one replacement. Moreover, what was reasonable a few decades ago may not be reasonable today [25].
Jia-Wei-Xiao-Yao-San is usually prescribed to treat insomnia, depressive disorder, anxiety disorder, and functional dyspepsia [26,27]. It can decrease serotonin and interleukin-6 and has been reported to have an antidepressant-like effect [28,29]. Chai-Hu-Shu-Gan-San can soothe the liver and regulate Qi and is also used to treat anxiety and depression, especially poststroke depression and postpartum depression, according to Yan Sun's research [13,30]. In addition, Chai Hu (Bupleurum chinense DC.), Xiang Fu (Cyperus rotundus L.), and Chuan Xiong (Ligusticum striatum DC.), which are part of the composition of Chai-Hu-Shu-Gan-San, also have anti-inflammatory effects [13]. Cooklin et al. [31] investigated the link between physical health, breastfeeding problems, and maternal mood and found that the presence of breastfeeding problems was associated with poorer maternal mood. Fallon et al. [32] reviewed the relationship between postpartum anxiety and infant-feeding outcomes, and their results indicated that postpartum anxiety increases breastfeeding difficulties. Webber and Benedict [33] investigated the relationship When it comes to the most prescribed Chinese herbs for mastitis, many of these prescription herbs are used to rectify Qi, clear heat, resolve toxins, disperse swelling, and relieve pain. e possible pharmacological effects of Chinese herbs are obtained from the scientific literature by PubMed and are listed in Table 2.
Mai Men Dong nourishes Yin and generates fluid and, therefore, is used as a typical treatment for Yin deficiency, dry mouth, fluid depletion, and constipation [34]. Women's constitution transferred throughout the perinatal period. A previous study revealed that Yin-Xu constitution worsened during pregnancy and did not recover at six months postpartum [35]. e use of Mai Men Dong may also ameliorate some postpartum physical symptoms, such as sweating, thirst, and constipation [36,37]. Furthermore, Yi Xue Qi Yuan, an ancient Chinese medical text, describes that Mai Men Dong is also used to treat lactation. In addition, Mai Men Dong had been proved to have anti-inflammation effects [10].
Pu Gong Ying can clear heat toxins and relieve swelling. It has anti-inflammatory and analgesic effects and has been used to treat upper respiratory tract infections, urinary tract infections, hepatitis, and dyspepsia [11]. Wang Bu Liu Xing is effective in activating blood circulation and reducing swelling, has analgesic and anti-inflammatory effects [12], and is used to treat female mammary gland diseases and promote lactation.
In this study, we found that the mastitis rate in Taiwan was much lower compared with that reported by previous studies. is underestimation might be due to the use of health care services. In Taiwan, women with mastitis usually opt for Western medicine, breast massage, or consultation with international board-certified lactation consultants. Among these treatments, the National Health Insurance does not cover breast massage or international board-certified lactation consultants; therefore, these women were not included in the study.
is study was designed to explore the prescription of TCM for mastitis in Taiwan. We found that certain Chinese medicines have anti-inflammation and analgesic effects for treating mastitis, similar to Western medicine. Furthermore, Chinese medicine rarely causes stomach pain, diarrhoea, or indigestion and may be a possible alternative for treating mastitis.

Limitations
ere are two limitations to this study. First, due to the feature of the LHID, we could not differentiate the aetiology of mastitis. Nevertheless, the 10 most prescribed CHM products were compliant with the clinical treatment of lactation mastitis. Second, mastitis is diagnosed by clinical symptoms and signs, and most patients had a good prognosis after receiving appropriate treatment, so it is hard to evaluate the efficacy of the treatment.

Future Perspectives and Priorities
is study discussed the prescription patterns of Chinese herbal medicine products in women with mastitis in Taiwan. However, a well-conducted, randomized controlled trial should be conducted to further evaluate the efficacy of TCM treatment for mastitis.

Conclusions
e present study provides preliminary clinical evidence supporting the prescription patterns of CHM products in women with mastitis. Approximately 5.1% of women with mastitis received CHM as complementary treatment. Xian-Fang-Huo-Ming-Yin is the most frequently prescribed Chinese herbal formula in these cases. Further welldesigned, clinical trials could be developed to evaluate the effectiveness of TCM for mastitis.

CHM:
Chinese herbal medicine ICD-9-CM: International Classification of Diseases, 9th Revision, Clinical Modification LHID: Longitudinal Health Insurance Database NHIRD: National Health Insurance Research Database TCM: Traditional Chinese medicine TWD: Taiwan dollars.

Data Availability
e data used to support the findings of this study are included within the article.

Conflicts of Interest
e authors declare that there are no conflicts of interest.

Authors' Contributions
SHC designed the study, and PJC supervised the project. CCH performed the data analysis. SHC drafted the manuscript. PJC, CCH, CHL, and KCW gave feedback on the manuscript.