Evidence-Based Medicine Research on Shanghan Zabing Lun Prescriptions in the Treatment of Endometriosis

Objective: Adopting the methods of Evidence-based Medicine research to acquire the dominant prescriptions of Shanghan Zabing Lun in the treatment of Endometriosis, meanwhile to fully dig the value of classical prescriptions. Method: Firstly, we searched and collected the literatures from last three decades in CNKI, Wanfang and VIP databases, which are about classical prescriptions treating endometriosis. Then, by screening all the literatures, we obtained the clinical research literatures and individual case reports. Finally, we went through the internal quality of the two categories of literatures to get the dominant prescriptions. Results: 22 Shanghan Zabing Lun prescriptions have been used in the treatment of endometriosis. According to the clinical research and case literatures, Guizhi Fuling Wan is the prime prescription to treat endometriosis with high quality and high frequency. Conclusions: Through evidence-based medical research and evaluation of evidence, it can be seen that treatment of endometriosis presents a certain tendency that Guizhi Fuling Wan, Wenjing Decoction and Dahuang Zhechong Wan have good clinical effect treating endometriosis and their syndromes are well matched with the symptoms of endometriosis in the present clinical environment.


Introduction
Endometriosis is one of the most common gynecological diseases, affecting many women's lives and many women were troubled by it [1]. Understanding the causes is essential to treat endometriosis. One of the reasons for endometriosis is congenital re-productive organs dysplasia, including uterus atresia, transverse vaginal septum, atresia hymenalis and malposition of the uterus. Also, this can be acquired from abortions, uterus or vaginal surgeries, vaginal drug use, which can result in adhesions of cervix, vagina and introitus. Because of the above pathological states, menstrual blood cannot be eliminated from the body, leading to menstrual blood refluxing into the pelvic cavity.
The treatments in western medicine commonly apply minimally invasive surgeries or medication, while Chinese medicine has good curative effect for endometriosis except caused by congenital reproductive organs dysplasia. By applying evidence-based medicine retrospective study from 1979 to 2013, the following formulas have good curative effect for the disease. Endometriosis belongs to the range of dysmenorrhea, infertility, menstrual disorders and abdominal mass in Traditional Chinese Medicine, which are more often the results of the imbalance between the Chong and Ren Meridians, qi and blood stasis, long-term menstrual abnormalities caused by emotion damage, diet disorders, and unhealthy daily habits. Table   In Table 1 and Table 2

Prescriptions and Quality Level in Clinical Research Literatures
Evidence-based medicine commonly refer to GRADE standard to evaluate quality of literatures, whereas Evidence-based medicine research in Traditional Chinese Medicine cannot ponderously apply the exact same items. Consequently, the following quality  level identification is based on a modified GRADE standard that was discussed and recognized by several rounds of professionals, adding four items of the standard which are: addition or subtraction of prescriptions, the original does and composition of the prescription, using Shanghan Zabing Lun prescriptions only and whether researches and cases are from before the year of 1979. The rest of items are the same as in GRADE standard [2]. Detailed information is shown in Table 3.

Guizhi Fuling Wan
59 papers are included in total, 28 of which are randomized controlled trials, 5 are half randomized controlled trials, 8 are controlled trials, and 18 cases series observations. All the documents were published between 1992-2013. Quality grade evaluation of evidence is shown in Table 4. It shows that there are 14 pieces of high (H) quality evidence, 17 of medium (M) quality, 12 of low (L) quality, 16 of very low (VL) quality. Evidence quality level degrading factors mainly are the research limitations ①, addition or subtraction of prescriptions ②, low accuracy ③ and indirect evidence ④. Evidence quality level upgrading factors mainly are using the original prescription of Shanghan Zabing Lun ⑤, or only using traditional Chinese medicinal intervention ⑥.

Dahuang Zhechong Wan
6 papers are included in total, 2 of which are randomized controlled trials, 1 is controlled trials, and 3 cases series observations. All the documents were published between 1998-2001. Quality grade evaluation of evidence is shown in Table 5. It shows that

Didang Decoction
4 papers are included in total, 2 of which are randomized controlled trials and 2 cases series observations. All the documents were published between 2003-2012. Quality grade evaluation of evidence is shown in Table 6. It shows that there are 3 of low (L) quality, 1 of very low (VL) quality. Evidence quality level degrading factors mainly are the research limitations ① and addition or subtraction of prescriptions ②. Evidence quality level upgrading factors mainly is using traditional Chinese medicinal intervention ⑥.

Wenjing Decoction
3 papers are included in total, 2 of which are randomized controlled trials and 1 is controlled trials. All the documents were published between 1998-2012. Quality grade evaluation of evidence is shown in Table 7

Typical Clinical Evidence
There

Dahuang Zhechong Wan
Dahuang Zhechong Wan combined with Gestrinone contrasting mere Gestrinone in the treatment of endometriosis has advantages in clinical total effective rate (high quality evidence

Wenjing Decoction
WenJing Decoction contrasting Medroxyprogesterone Acetate in the treatment of endometriosis has advantages in clinical total effective rate (high quality evidence

The Analysis of Dominant Prescriptions Treating Endometriosis
Endometriosis is a common disease in urogenital system, nowadays, its incidence has been increasing due to rising multipled-pressure in modern society and changed of people eating habits and etc. Based on the principle of TCM syndrome differentiation and treatment, the disease attributes to different disease syndrome. dometriosis is a relatively low frequency disease in Wenjing Decoction treating spectrum. There are 1 piece of high quality evidence, 2 of medium quality reports in Wenjing Decoction related papers. Three controlled clinical trials have shown that combination therapy of WenJing Decoction and western medicine treating endometriosis is superior to the simple application of gestrinone, medroxyprogesterone acetate, mifepristone and etc. Outcomes are observed mainly on the improvement in clinical symptoms, the improvement of the ultrasound examination. Although the blood stasis is a common pathogenesis of the disease, coldness in body is also a main pathogenesis. Although the evidence is limited, this card type is used for reference. It still can be reference to use coming to the certain disease syndrome.

Other Prescriptions
There is less documentary evidence or low quality or less frequency for other prescriptions, such as Danggui SiNi plus Wuzhuyu Shengjiang Decoction, Shenqi Wan, Huangqi Guizhi Wuwu Decoction, Taohe Chengqi Decoction, Danggui Shaoyao Powder, Biejiajian Wan and etc. The pathogenesises the above prescriptions' syndromes stand for lack of enough evidence to support, but still have curative effect on the disease clinically, they can be used to refer to. More strong evidence from more researchers in the future is expected to improve the curative effect of the disease.

Conclusions
According to the analysis of existing literature evaluation, it shows that clinical types of endometriosis are: Guizhi Fuling Wan syndrome and Didang Decoction syndrome standing for the pathogenesis of stagnation of blood stasis, Dahuang Zhechong Wan syndrome standing for pathogenesis of consumptive internal injuries and blood stasis, Wenjing Decoction syndrome standing for pathogenesis of Chong-Ren coldness and stagnation of blood stasis, Xiayuxue Decoction syndrome standing for pathogenesis of heat and blood stasis.
By evidence-based medicine research and evaluation of evidence, extracting endometriosis treated with prescriptions from Shanghan Zabing Lun presents certain trends.
And prescriptions above are likely to be the main syndrome types in endometriosis in current clinical situation (Figure 1).