Research Review of Chinese Herbs for Endometriosis

INTRODUCTION

Literature review: Medical and Chinese medicine

Endometriosis is an under-diagnosed, under-reported and under-researched illness affecting women of all ages and ethnic groups. In order to best treat our patients with Chinese herbal medicine (CHM), we need to acknowledge the full scope of this illness. This study covers a comprehensive understanding of endometriosis in terms of aetiology and pathogenesis, current treatments available and their efficacy from both a Western medical and Chinese medicine (CM) perspective.

The scope of the research was obtained from electronic databases and some renowned Chinese medicine literature. Essential databases used included PubMed, AMED (allied and complimentary medicine database), SCOPUS (Elsevier) and the Cochrane library.

There are essential aspects of this disease that will be discussed, beginning with its definition and epidemiology. The aetiology and pathophysiology of endometriosis from both a medical and CM perspective is fascinating considering it is still being postulated. The main significance of this report entails how endometriosis is currently managed and what complimentary treatments women seek out to treat it. We then delve into the differential diagnosis from a CM perspective and lastly evaluate the effective management of endometriosis with CHM. Although research is largely studied from a medical perspective in mind, this paper will specifically focus on how to differentiate and treat it with CM and CHM.

Definition, Prevalence and the Impacts of Endometriosis

Endometriosis is a benign, chronic, oestrogen-dependent inflammatory, gynaecological illness defined by the presence of extra-uterine endometrial tissue in the abdominal cavity that affects women of reproductive age with pain, subfertility and quality of life (Cea Soriano, Lopez-Garcia, Schulze-Rath & Garcia Rodriguez, 2017). It is under-diagnosed, under-reported and under-researched (Moradi, Parker, Sneddon, Lopez, & Ellwood, 2014). It occurs in all women of all ethnic and social groups. It has no cure nor guarantee that it will not return (Denny & Mann, 2007).

The disease affects 10% of females of reproductive age and 35-50% of women with pelvic pain and infertility. Common signs and symptoms are dysmenorrhoea, dyspareunia and chronic pelvic pain (Giudice, 2010). In terms of epidemiology, it affects millions of women world-wide (Becker et al., 2017). The cardinal symptom is pain, which severely impacts the life of the affected women, their partners, families and their socioeconomic position (de Graaff, 2013). Negative impacts women with endometriosis face include reduced fertility, emotional pain due to sub-fertility, chronic pain, fatigue, sexual and marital relationship issues, anger about the disease returning and dyspareunia (Moradi et al., 2014).

AETIOLOGY & PATHOGENESIS OF ENDOMETRIOSIS

From a scientific perspective, the aetiology of endometriosis is complex and multifactorial, where several theories postulate its origins. In 1927, John Sampson theorised that retrograde menstruation allowed the cyclical arrival of endometrial cells in the abdominal cavity and since has been the aetiopathogenesis of endometriosis (Dastur & Tank, 2011). Current medical literature indicates that stem cells, dysfunctional immune response, hereditary factors and an aberrant peritoneal environment all play a part in the establishment and spreading of endometrial lesions (Sourial, Tempest & Hapangama, 2014).

Another old theory pertains to coelomic metaplasia, where endometriosis develops from extra-uterine cells that abnormally transdifferentiate into endometrial cells. These cells exist in the mesothelial lining of the visceral and abdominal peritoneum (Gruenwald, 1942). A hormonal theory hypothesises that environmental toxins that mimic oestrogen such as dioxin and xenoestrogens enhance the development of endometriosis (Parente Barbosa, Bentes De Souza, Bianco & Christofolini, 2011). Oxidative stress and inflammation has also been proposed as an aetiological factor. The substantial oxidation of lipoproteins has been linked with the pathogenesis of endometriosis given reactive oxygen species cause lipid peroxidation that subsequently damages the DNA of the endometrial cells (Murphy, Palinski, Rankin, Morales & Parthasarathy, 1998). Further theories extend to immune dysfunction, apoptosis suppression, genetics and stem cells (Sourial et al., 2014).

Scientists have found that immunological alterations within peritoneal fluid explains how the endometriosis affects the body but not how it originates (Laganà et al., 2017). Laganà et al (2017) suggest that this occurs during embryological development, whereby ectopic müllerian remnants of the endometrium, endocervix and endosalpinx leaked during organogenesis from the genital ridge. A genetic theory proposes that immune cells and other pro-inflammatory substances create the conditions for differentiation, adhesion and proliferation of ectopic endometrial cells. Ultimately, the aetiology and pathogenesis of endometriosis is not known with certainty (Sourial et al., 2014).

Chinese Medicine & Endometriosis

In China & Taiwan, endometriosis is routinely treated with CM often in the form of CHM (Tsai et al., 2017). CHM has its own terminology and more traditional theories reason the cause and development of endometriosis. CM regards endometriosis as a disease of blood stagnation which can be caused over a long-term scale by numerous habits such as intercourse during menstruation, intercourse during and before puberty, excessive physical work or exercise, invasion of external cold, tampon use, emotional stress and irregular or poor diet (Maciocia, 2011, p.858). Stress is a major factor as it stagnates qi in the liver channel which encircles the genitals.

In terms of CM pathology, underlying kidney deficiency with a disharmony of liver and spleen prevail. Retention of the menses, whereby not all of the menstrual blood is expelled period after period is believed to cause endometriosis. The appearance of endometrial lesions when examined surgically are always purple, dark red or purple-blue; indicating that the blood has stagnated. Women with a blood stagnation pattern are more likely to develop endometriosis. Kidney deficiency is always an underlying pattern given the body is weak to the extent it cannot move the blood thus it stagnates. Other pathological factors that encourage the proliferation of endometriosis include cold, phlegm-damp and dampness (Maciocia, 2011, p.859).

CURRENT MANAGEMENTS OF ENDOMETRIOSIS

Medical intervention can alleviate endometriosis associated pain, however the relief is limited to efficacy and duration with symptoms usually recurring after the cessation of treatment (Dunselman et al, 2014). Medical treatment aims to suppress local or systemic oestrogen, reduce pain and provide direct hormonal effects on endometrial lesions. Treatment is determined by the patients age, severity of symptoms and stage of endometriosis and whether fertility is desired.

Pain medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are widely given for analgesia. Endometrial lesions can be treated by the suppression of endogenous hormones with progestins such as the mirena or intrauterine device (IUD) and combined oral contraceptives (COCs), although side effects range from irregular bleeding, breast tenderness to mood disturbances (Crosignani, Olive, Bergqvist & Luciano, 2006). Danazol treatment prevents the release of hormones that control the menstrual cycle however its side effects are harsher than previous hormonal treatments. Aromatase inhibitors reduce the amount of oestrogen available in the body. Restricted medications include gonadotropin-releasing hormone (GnRH) agonists are usually prescribed for short-term use as they induce a hypo-oestrogenic state and decrease bone mineral density (Lee et al., 2016).

Surgery is a common intervention. Endometrial lesions are treated by means of surgical ablation or excision (laparoscopy). Laparotomy and surgeries to sever pelvic nerves such as presacral neurectomy and laparoscopic uterine nerve ablation (LUNA) are no longer considered effective in the treatment of endometriosis (American College of Obstetrics and Gynaecology, 2010).

Complementary therapies that are used to treat endometriosis include hypnotherapy, Chinese medicine (acupuncture, auricular acupuncture, Chinese herbal medicine, tui na), naturopathy, homeopathy, yoga, qi gong and nutrition along with lifestyle changes (Fisher, Adams, Hickman & Sibbritt, 2016).

DIFFERENTIAL DIAGNOSIS IN CHINESE MEDICINE & TREATMENTS

Fundamental to the understanding of endometriosis in CM the notion of stagnation of qi or vital energy which reflects the subjective symptom of pain and of blood, tends to localise and intensify the experience of pain and thus can lead to the formation of proper, established lesions (Flower, Liu, Lewith, Little & Li, 2012). There is always underlying kidney deficiency. The kidney energy supports the entire reproductive system.

In CM, endometriosis is classified as ‘painful periods’ and ‘abdominal masses’ (Maciocia, 2011, p.861). Illness is always assessed through pattern identification and although endometriosis is one type of disease, patients with endometriosis will always present with varying patterns. Differential diagnosis is taken holistically on the basis of information derived from traditional methods of clinical assessment such as tongue and pulse diagnosis, abdominal palpation, the subjective presentation of the type and expression of the pain from the endometriosis, from an evaluation of the general health of the patient from sleep patterns and digestive status to the subjective senses of temperature. This detailed and involved process is considered essential to identifying the patient’s pattern and the successful treatment of the illness.

These patterns include liver blood stasis, stagnation of cold, dampness, damp-phlegm in the uterus, kidney yang deficiency, kidney yin deficiency, blood deficiency and combined patterns such as blood stasis, dampness with kidney yin or yang deficiency. For example, a severe case of endometriosis at stage IV with large lesions could be classified as blood stasis with kidney yang deficiency and damp-phlegm in the uterus (Maciocia, 2011, p.862-877). Most of the following Chinese herbal formulae will treat the underlying pattern with herbs that are categorised as ‘blood moving’ (Flower et al., 2012).

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Liver blood stasis requires tonification and movement of blood, using herbal formulae such as Da Qi Qi Tang, Nei Yi Fang and Hua Yu Ding Tong Tang. Stagnation of cold calls to warm the uterus, expel cold and invigorate the blood with Wen Jing Tang. When an endometriosis pattern falls into the category of dampness, treatment aims to resolve the dampness and move the stasis. Qing Re Tiao Xue Tang and Er Miao San do this. When there is damp-phlegm in the uterus then treatment aims to resolve the damp and phlegm, move qi and invigorate the blood with Cang Fu Dao Tan Wan. Kidney yang deficiency calls to tonify and warm the yang, and invigorate the blood with Gui Yin Jian and You Gui Wan. When the underlying pathology is kidney yin deficiency, treatment aims to nourish yin and tonify the kidneys with Zuo Gui Yin. A blood deficiency pattern requires blood tonification so it can move blood and nourish the liver with Ren Shen Yang Rong Tang. Combined patterns will have combined and modified formulae accordingly (Table 1). Table 2 refers to some of the key herbs in CHM formulae for endometriosis.

Table 1. Chinese herbal formulae commonly used in the treatment of endometriosis

Pinyin name of formula Ingredients                  (Chinese herbs in Pinyin) TCM Indications
Cang Fu Dao Tan Wan Cang Zhu, Fu Ling, Chen Pi, Xiang Fu, Zhi Ke, Dan Nan Xing, Gan Cao, Sheng Jiang, Shen Qu Qi and blood stagnation with phlegm and dampness
Da Qi Qi tang Qing Pi, Chen Pi, Xiang Fu, San Leng, E Zhu, Jie Geng, Huo Xiang, Rou Gui, Yi Zhi Ren, Gan Cao, Sheng Jiang, Da Zao Qi and blood stagnation with phlegm and interior cold
Dang Gui Shao Yao San Dang Gui, Chuan Xiong, Bai Shao, Bai Zhu, Fu Ling, Ze Xie Liver blood deficiency and disharmony of liver and spleen
Dang Gui Jian Zhong Tang Dang Gui, Yi Tang, Gui Zhi or Rou Gui Xin, Bai Shao, Gan Cao, Sheng Jiang, Da Zao Spleen and stomach deficiency with abdominal pain
Dang Gui Si Ni Tang Dang Gui, Bai Shao, Gui Zhi, Xi Xin (banned), Da Zao, Zhi Gan Cao, Mu Tong Blood deficiency causing cold extremities
Er Miao San Can Zhu, Huang Bo, Bai Jiang Cao, Yan Hu Suo Damp-heat in the lower jiao
Gui Yin Jian Ren Shen, Shu Di Huang, Shan Yao, Shan Zhu Yu, Tu Si Zi, Yuan Zhi, Wu Wei Zi, Zhi Gan Cao Deficiency of blood, yin and yang with cold
Gui Zhi Fu Ling Wan

 

Gui Zhi or Rou Gui, Fu Ling, Bai Shao or Chi Shao, Mu Dan Pi, Tao Ren Blood stasis in the uterus (chong mai and ren mai)

 

Hua Yu Ding Tong Tang Dang Gui, Dan Shen, Chuan Xiong, Chuan Niu Xi, Chi Shao, Xue Jie, Mo Yao, Su Mu, Yan Hu Suo, Wu Ling Zhi, Pu Huang, E Zhu Severe blood stagnation with pain
Nei Yi Fang Xiang Fu, Dang Gui, Dan Shen, Xue Jie, Chuan Niu Xi, Chi Shao, E Zhu, Gui Zhi, Zao Jiao Ci, Hai Zao Specifically created for endometriosis and to break up masses
Qing Re Tiao Xue Tang Xiang Fu, Chuan Xiong, Hong Hua, Tao Ren, E Zhu, Yan Hu Suo Blood stagnation with heat
Ren Shen Yang Rong Tang Bai Shao, Ren Shen, Dang Gui, Shu Di Huang, Huang Qi, Bai Zhu, Fu Ling, Zhi Gan Cao, Rou Gui, Chen Pi, Yuan Zhi, Wu Wei Zi, Sheng Jiang, Da Zao Qi and blood deficiency (heart and spleen deficiency)
Shao Fu Zhu Yu Tang Xiao Hui Xiang, Gan Jiang, Rou Gui, Dang Gui, Chuan Xiong, Mo Yao, Yan Hu Suo, Pu Huang, Wu Ling Zhi Qi stagnation and blood stasis in lower abdomen due to excess cold
Shi Xiao San Pu Huang, Wu Ling Zhi Blood stasis in the lower abdomen causing pain
Tao He Cheng Qi Tang Tao Ren, Da Huang, Gui Zhi, Mang Xiao, Zhi Gan Cao Blood stagnation with mania
Wen Jing Tang Wu Zhu Yu, Gui Zhi, Dang Gui, Chuan Xiong, Bai Shao, Mu Dan Pi, E Jiao, Mai Men Dong, Ren Shen, Zhi Ban Xia, Sheng Jiang, Zhi Gan Cao Deficient cold and blood stasis
Xiao Yao San

 

Chai Hu, Dang Gui, Bai Shao, Bai Zhu, Fu Ling, Zhi Gan Cao, Pao Jiang, Bo He Liver qi stagnation and spleen (and blood) deficiency

 

 

Xue Fu Zhu Yu Tang Tao Ren, Hong Hua, Chuan Xiong, Sheng Di Huang, Dang Gui, Chi Shao, Chai Hu, Zhi Ke, Gan Cao, Niu Xi, Jie Geng Blood stagnation in the chest
Yang He Tang Rou Gui, Pao Jiang, Shu Di Huang, Lu Jiao Jiao, Bai Jie Zi, Ma Huang (banned), Gan Cao Yang and blood deficiency with cold and blood stagnation
You Gui Wan Zhi Fu Zi (banned), Rou Gui, Lu Jiao Jiao, Shan Zhu Yu, Du Zhong, Shu Di Huang, Gou Qi Zi, Tu Si Zi, Dang Gui, Shan Yao Kidney yang deficiency
Zuo Gui Wan Shu Di Huang, Gou Qi Zi, Shan Zhu Yu, Lu Jiao Jiao, Gui Ban (banned), Chuan Niu Xi, Tu Si Zi, Shan Yao Kidney yin deficiency

Professor Huang, a renowned classical herbalist of China, recommends Xiao Yao San for the treatment of endometriosis when the patient’s presentation matches this particular pattern. Other formulae he recommends for dysmenorrhoea and blood stagnation include Yang He Tang, Dang Gui Jian Zhong Tang, Tao He Cheng Qi Tang, Dang Gui Si Ni Tang, Gui Zhi Fu Ling Wan, Wen Jing Tang and Xue Fu Zhu Yu Tang (Huang, 2009, p.285). Instead of Xue Fu Zhu Yu Tang, Shao Fu Zhu Yu Tang would be a more appropriate formula for blood stagnation in the uterus. Table 1 refers to these formulae mentioned above for further reference.

Table 2. Herbs frequently cited in complex herb formulae for treatment of endometriosis (Dharmanadanda, 2002)

Herb (Pinyin name) Role in endometriosis therapy Description of use
Pu Huang

 

Invigorates the blood, reduces pain. When fried or carbonised it inhibits excessive menstrual bleeding. Almost always paired with Wu Ling Zhi, based on an ancient formula using equal parts of those two herbs, called Shi Xiao San.
Wu Ling Zhi

 

Invigorates the blood, reduces pain. Almost always paired with Pu Huang, based on an ancient formula using equal parts of those two herbs, called Shi Xiao San.
San Leng

 

Breaks static blood and reduces masses. Almost always paired with E Zhu to treat masses caused by blood stagnation.
E Zhu Breaks static blood and reduces masses. Almost always paired with San Leng to treat masses of blood stasis.
Chi Shao Invigorates blood circulation. Usually paired with either Dan Shen or Mu Dan Pi or both to improve blood circulation.
Huai Niu Xi or Chuan Niu Xi Invigorates blood circulation. Huai Niu Xi nourishes the blood and aids circulation; Chuan Niu Xi has similar effects but is usually used for more severe blood stasis.
Dan Shen

 

Invigorates blood circulation. Usually paired with either Chi Shao or Mu Dan Pi or both to improve blood circulation.
Chai Hu

 

Regulates qi circulation, which promotes circulation of blood. Usually paired with Xiang Fu to treat qi and blood stagnation in the lower abdomen.
Xiang Fu Regulates qi circulation, alleviates pain. Usually paired with Chai Hu to invigorate circulation.
Tao Ren

 

Breaks up static blood to relieve pain. Usually paired with either Mu Dan Pi, Da Huang, or Hong Hua to invigorate blood circulation; Da Huang with Tao Ren also has a laxative effect.
Dang Gui

 

Tonifies blood, circulates blood and improves qi circulation. Usually paired with Bai Shao or Chai Hu or both to improve circulation of qi and blood.
Chuan Xiong

 

Invigorates blood circulation and alleviates pain. Usually paired with Dang Gui to treat pain and regulate menstruation.
Gui Zhi (or Rou Gui)

 

Improves circulation, warms the body and alleviates pain. Usually paired with Dang Gui, Bai Shao, or Chi Shao to improve circulation and relieve pain.
Zao Ci Resolves swellings. Typically used for abscesses and other swellings.
Mu Li Softens masses. Commonly used for abdominal masses.
Yan Hu Suo

 

Invigorates blood circulation and alleviates pain. Indicated for abdominal pain.
Da Huang

 

Invigorates blood circulation, relieves swellings, laxative effect and when carbonised, inhibits bleeding. Usually combined with Tao Ren for abdominal masses and constipation.
Zhe Chong

 

Breaks up static blood and relieves pain. Combined with Da Huang and Tao Ren in the ancient formula, Da Huang Zhe Chong Wan, for the treatment of hardness and pain in the abdomen and excessive menstrual bleeding.

DISCUSSION: ANALYSIS AND MANAGEMENT USING CHINESE HERBAL MEDICINE

Chinese Medicine (CM) is one of the most commonly used complementary therapies to medical treatment in Asia within the paradigms of Chinese herbal medicine (CHM), acupuncture, moxibustion, cupping and tui na (traditional soft tissue massage). The type of treatment administered whether individually or collectively is based on the CM practitioner’s prescription (Tsai et al., 2017). One common recurring factor that was highlighted during research was that endometriosis is a disease with a complicated pathogenesis, and that CHM prescriptions for endometriosis are often so intricate and requiring regular modification as signs and symptoms change that more that CM practitioners will often combine several formulae into one (Chen et al. 2014).

Many studies have assessed the efficacy of CHM for endometriosis but few warrant mention here due to unofficial diagnosis of endometriosis (i.e. not laparoscopic confirmation), unequal group size with no account of randomisation process, non-validated outcome measures, pain is not considered as a primary outcome, control group was using another intervention and too many treatment variables combined from a CM perspective (Flower et al., 2012). This last point is a significant hurdle in research for CHM. Many studies are written in Chinese and this creates a barrier for their analysis in Australia for many practitioners.

Ji et al (2011) found the Chinese herbal formula Gui Zhi Fu Ling Wan effective for treating endometriosis and Flower et al. (2012) also noted efficacy with the combination of oral Chinese herbal medicine with a herbal enema. Dharmanadanda (2002) mentions Shi Xiao San for active pain phases of endometriosis. Also recommended is the isolated herb Wu Ling Zhi being made into an ointment to apply topically on the abdomen to alleviate pain.  One study of high quality research demonstrated that CHM provided the same amount of symptomatic relief as gestrinone, without the numerous adverse effects that this drug had (Wu, Chen & Chen, 2006a).  Both CHM formulae Nei Yi Wan and Nei Yi Wan plus herbal enema groups had a greater portion of women having symptomatic relief than for danazol (Wu, Chen & Chen, 2006b).  No significant side effects were observed in the CHM group, whereas the vast majority of the danazol group did. A systematic review of high quality trials regarding medical interventions for endometriosis found GnRH, the IUD, danazol, laparoscopy, progestogens and anti-progestogens all to be effective when compared with a placebo (Brown & Farquhar, 2014).

Gui Zhi Fu Ling Wan has been found to significantly reduce the size of endometrial implants in rat models (Ji et al., 2011). One study which combined long-term use of Chinese herbs with hypnotherapy found a significant reduction in pain and the use of analgesics. Fifty-five percent of patients who were trying for a baby had successfully given live birth (Meissner, Bohling & Schweizer-Arau, 2010). This study had only 47 patients, lacked a control group and were followed up with standardised telephone interviews.

Most endometriosis studies have a gap in the lack of long-term monitoring for patient outcomes. Without knowing how effective medical intervention is on a long-term scale for both surgery and hormones translates poor to unknown efficacy given it is likely that patients will experience the return of signs and symptoms at 6 months or more. Common medications for treatment such as COCs and progestins were found to give a temporary alleviation of signs and symptoms whereas other medications such as GnRH agonists and danazol were functional but also produced harsh side effects (Becker, Gatrell, Gude & Singh, 2017).

This is where CHM has a strong potential to assist many sufferers of endometriosis; CHM can provide the same or better reduction in symptomatic pain that the previous mentioned medication without the adverse side effects that all have on the body. Further high quality trials are required to demonstrate this.

In clinical practice, I have found Xiao Yao San, Wen Jing Tang, Gui Zhi Fu Ling Wan, Dang Gui Si Ni Tang and Dang Gui Shao Yao San all to be effective in the reduction of symptomatic pain for endometriosis patients, along with teaching them essential lifestyle skills to manage the illness. – Ilana Sowter, Acupuncture Melbourne

CONCLUSION

Chinese herbal medicine (CHM) has been used for hundreds of years to effectively treat dysmenorrhoea, and what we can diagnose today as endometriosis. Current management of endometriosis with medical treatments are generally effective, however pose adverse effects and laparoscopic surgery does not always offer full symptomatic pain alleviation. CHM has been shown to provide the same and better results than medical treatments, providing the patient’s formula is tailored to their underlying diagnostic pattern with the addition of ‘blood moving’ herbs which is an essential protocol of CHM treatment for endometriosis. More studies of higher quality are required so that this can be reputably accepted in medical paradigms.

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