TREATMENT
OF ENDOMETRIOSIS WITH CHINESE MEDICINE
BACKGROUND
Endometriosis is defined as the occurrence of pseudocysts in response to endometrial tissue that is in the pelvic cavity other than as part of the endometrium. This tissue adheres to various pelvic organs, it responds to the hormones of the menstrual cycle, and sloughs tissue and blood as does the endometrium. The blood and displaced cells have no place to go, and the result is that layers of connective tissue develop in response to the confined fluid, and the resulting cysts can grow to considerable size. They are considered pseudocysts because they do not have an epithelial lining. The symptoms that can arise include increased menstrual bleeding, severe menstrual pain, pain on having intercourse, general pelvic pain (possibly due to adhesions), and changes in bowel conditions with menstruation (due to cysts adhered to the intestine; there can even be rectal bleeding). Endometriosis is suggested by such symptoms, but it is confirmed only by laparoscopy, which is the insertion of a small viewing tube into the abdomen. The endometrial cysts usually appear dark blue to brown (called “chocolate cysts” because of their color), or they may appear as lesions.
Endometriosis is one of the major causes of menstrual pain (dysmenorrhea). The first symptoms often occur two to three years after menarche, though sometimes are delayed if the cysts are small or if the biochemical changes associated with symptoms, such as unusual prostaglandin and endorphin levels, are not very great. According to retrospective studies, 41–43% of women with endometriosis report experiencing dysmenorrhea before age 20. Pain during periods eventually affects nearly all of those who have symptomatic endometriosis, and about 60% of these women also have pain between periods, with bowel movements, and/or with intercourse.
The heightened awareness of endometriosis is largely the result of the intense interest in treating infertility that developed during the 1980’s. Current estimates are that 30 to 47% of women suffering from this disorder are infertile. Endometriosis sometimes vanishes with a pregnancy, or disappears for a while afterward only to return later, and it fades with menopause. Estrogen replacement therapy can cause endometrial hyperplasia and stimulation of endometrial cysts, but combined therapies with progesterone and its derivatives avoid this problem.
The historical evolution of endometriosis is not known, but the disease was first defined in 1920, and there were around 20 reports about it in the worldwide literature in 1921. Examination of the earlier medical literature has suggested to some that the disorder had been found, even though not specifically identified, during the 19th century. It has taken some time for the disorder to gain recognition among the majority of medical practitioners. Women who go to doctors about menstrual pains (or other endometriosis symptoms) may not be diagnosed because the symptoms are believed by some doctors to be “normal” or to be exaggerated by the patient. During the 1980’s, women who had endometriosis symptoms in their teens experienced a delay of more than 8 years in receiving a diagnosis of endometriosis and often had to visit several doctors before gaining a diagnosis, despite an extensive literature on the subject and readily available laparoscopy.
Today, it is estimated that at least 5 million women in the U.S. alone have a symptomatic manifestation of endometriosis, and the worldwide level may be about 100 million. During laparoscopic evaluations of U.S. women with a variety of gynecological disorders (mainly pain and infertility) it has been found that up to 40% have one or more endometrial cysts. It appears that the incidence of endometriosis is rapidly increasing and that doctors are more frequently taking the steps to diagnose it.
The cause of endometriosis is not known, though older theories of back flow of menstrual blood with endometrial tissue gaining entrance to the abdominal cavity are giving way to new concepts. Studies with primates exposed to the toxic chemicals dioxin and polychlorobiphenyls (PCBs) show endometrial cysts, suggesting that the rapid increase in rate of detecting endometriosis is partly a result of the increased exposure to environmental pollutants during the past century. Autoimmune processes have been suggested to be involved, which may include autoimmune responses aimed at hormones and/or at components of the cysts. It has also been suggested that delayed childbirth is responsible for the rapid rise of this syndrome, since having early and repeated pregnancies, as was the case before the 1920’s, would likely halt the growth of any endometrial cysts that were present. Once the first pregnancy has been substantially delayed, the larger cysts are less likely to shrink after a pregnancy. It has also been reported that endometrial symptoms are more common among women with certain nutritional deficiencies, and that the symptoms could often be alleviated by supplementing with nutrients, such as B vitamins and magnesium.
Drug therapy for endometriosis is often unsatisfactory. Most of the current drug therapy is aimed at altering the hormones, for example, by giving the testosterone derivatives danazol or methyltestosterone, giving progesterone and related progestogens, or using Buserelin, Goserelin, Lupron or other Gn-RH antagonists (that cause ovarian inhibition). One can also use analgesics that block prostaglandins to relieve the severe dysmenorrhea. Surgical removal or aspiration of endometrial cysts usually provides only temporary benefits and may cause secondary problems, including persistent abdominal pain due to adhesions. Therefore, alternative treatments are of interest to those who suffer from endometriosis. The experience of Chinese doctors is instructive, as Chinese medical treatments have been reported to be highly successful and several of them can be obtained in the West.
Information about endometriosis, its possible causes, incidence level, diagnosis, symptoms, and treatments (1) is available from the Endometriosis Association, an organization established in 1980 with international headquarters in Milwaukee, Wisconsin. A large international Congress on Endometriosis is held at three year intervals.
THE SITUATION IN CHINA
Laparoscopy procedure was introduced into China around 1960, and reports about this disease first appear in the literature soon after that. The incidence of endometriosis in China, like that in the U.S., is reportedly increasing (2). Up to 30% of patients undergoing pelvic laparotomies for any reason are found to have endometrial cysts, and these procedures have increased during the past three decades from 3.8% to more than 10% of admissions to the large Beijing Union Medical College Hospital. 70% of the patients undergoing the procedure are under age 30. About 13% of women in China between the ages of 18 and 25 suffer from dysmenorrhea, of which a substantial portion—perhaps half—is due to endometriosis. In an evaluation of more than 1,500 infertility women it was found that about one-third of them had endometriosis.
In China, endometriosis is called neiyi, or internal lump. This is a new term, because the lump is actually not detected except by laparoscopy. Generally, to whatever extent endometriosis may have existed in the past, it was treated according to the dominant symptom, which was usually abdominal pain, especially menstrual pain. That condition, and its treatment by herbs, is mentioned in the ancient book Jin Gui Yao Lue (Prescriptions of the Golden Cabinet), written around 220 A.D.
Before reviewing the traditional herbal treatments, the intensive investigation into a new herbal drug, gossypol, will be reviewed. Research into its use for endometriosis began in 1979.
GOSSYPOL THERAPY
A review of gossypol research was published in Recent Advances in Chinese Herbal Drugs (2) and information here comes from that review plus several abstracts of recent studies published in Abstracts of Chinese Medicine (3).
Gossypol is the active component of cotton roots and seeds that is being used extensively in China as a male contraceptive. Its action in this application is not via a hormonal mechanism, but rather by interfering with cellular regulation mechanisms. It is also used for treating female gynecological disorders such as uterine myoma and menopausal bleeding, and it does function partly via a hormonal mechanism in these cases. All these applications were determined after it was found that men became sterile and that women experienced atrophy of the uterus and amenorrhea when they used crude cottonseed oil in cooking over an extended period of time. The fact that gossypol was then shown to cause atrophy of endometrium led clinicians to test it for treatment of endometriosis.
Several studies over a 15 year period have shown that the short-term effectiveness of gossypol for endometriosis is close to 90%, and that long-term effects—one to three years after treatment—are maintained in 54–63% of those treated. Its use relieves symptoms of menorrhagia and dysmenorrhea and can result in persisting reduction of endometrial cysts and uterine myomas. Following a typical treatment of several months duration, a majority of women will also have amenorrhea which persists for up to six months (in about 80% of women treated), and up to a year (in 16% of those treated); a small number (4%) have amenorrhea lasting beyond one year.
There are two methods of administering gossypol, a high-dosage short-term therapy, in which the beneficial effects are more rapidly experienced but there is higher incidence of side effects, and a lower dosage longer-term therapy that has nearly as good a response after some delay, with fewer side effects. Both methods produce close to total relief of symptoms and signs of endometriosis. When endometrial nodules were examined, 91% completely or partially resolved in the high dosage group, but only 76% resolved in the low dosage group. Coexisting myomas were reduced in size in about 90% of patients using the high dosage regimen and in nearly 85% of those using low dosage. Using a high dosage regimen, 83% of a test group experienced amenorrhea, while in the lower dosage group only 62% experienced this effect.
A frequently cited side effect of gossypol (which is severe in about 10% of cases) is hypokalemia (potassium deficiency). The drug strongly promotes potassium secretion, and in high dosage is suspected of impairing renal tubule function. The problem can be counteracted by using slow-releasing potassium salt, which is now standard procedure in China, and also by relying on the lower dosage method. When using the high-dosage program, there is some tendency for liver enzymes to elevate (indicating liver dysfunction), but this occurs only rarely with the lower dosage. The high dosage program can also cause nausea, edema, and palpitation. Nonetheless, very high doses of gossypol administered to female rats did not cause any histological or morphological changes in the liver, kidneys, adrenals, or heart. Other side effects of the drug include skin rash (possible allergic response), poor appetite, and tiredness (gossypol may inhibit both thyroid function and mitochondrial energy metabolism).
Gossypol is reported to antagonize the action of estrogen and progesterone, and alter other hormone levels, and may thus cause some symptoms characteristic of menopause during prolonged use; the effect of gossypol on endometrial tissues is not, however, purely a result of the anti-estrogenic action. These hormonal and functional alterations, including amenorrhea, are positively correlated with the cumulative dose of gossypol ingested, and eventually return to normal. It is possible that a course of gossypol therapy has an impact on endometriosis similar to a pregnancy.
In a clinical trial of gossypol for endometriosis (31 cases), functional uterine bleeding (117 cases), and uterine myoma (44 cases), reported in the Chinese Journal of Integrated Traditional and Western Medicine (1988), all the cases of endometriosis were effectively treated and more than 90% of the women with the other gynecological disorders also had satisfactory results. Gossypol acetate was taken 20 mg once daily, and 10% potassium citrate (10 ml, thrice daily) was used to counteract the tendency to hypokalemia. Treatment time was just two to three months. Amenorrhea occurred in 75% of the women. In another study reported in the Chinese Journal of Integrated Traditional and Western Medicine (1989), gossypol acetate was administered to 12 women with endometriosis at 20 mg once daily for just 10 weeks and then 20 mg twice per week for several more weeks (total time 5–6 months), thus following a particularly low-dosage method for most of the treatment. It was noted that dysmenorrhea disappeared and endometrial cysts shrank in most cases; basal body temperature became monophasic and amenorrhea still occurred. Serum levels of luteinizing hormone and follicle-stimulating hormone increased. Progesterone decreased but estradiol and prolactin were unaffected. Histochemical and cytological observations revealed that the activity of phosphatases and esterases in both ectopic endometrium and endometrium in situ were decreased.
Gossypol is not readily available for use in the West and would need to be introduced as a drug product (which is highly unlikely) rather than an herb product if imported from China. The effects of gossypol have been compared in China to that of danazol, a drug that has been used in the U.S.; the latter is faster acting, but its action is less sustained; danazol has more side effects (such as obesity and strong androgenic effects) than gossypol. It should be noted that cotton roots have been utilized in the southern part of the United States in folk medicines for nearly 200 years to treat dysmenorrhea, amenorrhea, and uterine tumors.
The information about gossypol has been described here in some detail to demonstrate the success rates, dosage, and side effects, which will serve as a basis for comparison with other approaches. The main alternative to gossypol in China, which is also available now in the West, is the use of complex herb formulas. These formulas usually do not cause substantial side effects, though it is always possible to experience gastro-intestinal disturbances from the ingestion of almost any herbal combination (especially at higher dosage ranges) and a small number of individuals may experience allergy or hypersensitivity reactions.
COMPLEX FORMULAS FOR STAGNANT BLOOD
The use of non-toxic complex herb formulas for endometriosis has been discussed by several Chinese physicians. According to the theories of traditional Chinese medicine, blood stasis syndrome is the one which most closely matches the symptoms of endometriosis. Blood stasis is believed to be the cause of severe pain, especially lower abdominal pain, and it is believed responsible for many cases of excessive menstrual bleeding and infertility. The underlying causes of the blood stasis are mainly the syndromes of qi stagnation and coldness, but may also include a heat syndrome. Therefore, when applying the ideas of traditional Chinese medicine, endometriosis will usually be treated by herbs that vitalize blood circulation as the primary therapy, with additional herbs to address the underlying cause as well as to address any concurrent syndromes (e.g., qi deficiency) or specific symptomatic manifestations (e.g., to reduce bleeding in cases of menorrhagia).
Shanghai is one of the main centers of research for the application of traditional Chinese medicine for gynecological disorders. The Hospital of Obstetrics and Gynecology of the Shanghai First Medical College has been in the forefront of much of the research. In 1975, they held a conference to develop criteria for evaluating the effectiveness of treatments for gynecological disorders, including endometriosis. There was a rush of research work on endometriosis in Shanghai during the period 1979–1982.
In 1980, researchers at the Obstetrics and Gynecology Hospital published the first report (4) of a large scale clinical trial of Chinese herbs for endometriosis. The 156 patients were divided into three groups according to syndrome and given one of three possible treatments. Group one was given a combination of sparganium, zedoaria, gleditsia spine, cyperus, bupleurum, tang-kuei, bulrush (typha), and pteropus in decoction, plus an “endometriosis powder” made with earthworm, tabanus, centipede, and leech. Bulrush and pteropus together represent an ancient two herb combination widely used for treating severe abdominal pain; the Chinese name for the combination means the formula for returning the smile. Sparganium and zedoaria is a modern combination given for the treatment of lumps due to blood stasis; the pair is commonly found in tumor formulas. Bupleurum, cyperus, and tang-kuei are traditionally used to treat blood stasis that is caused by an underlying syndrome of qi stagnation, that is, a disorder in the circulation usually caused by emotional factors. Gleditsia spine is used to treat swellings. The insects and leech in the endometriosis powder disperse stagnant blood and relieve pain. In all, this is a very logical combination if one applies the traditional thinking about disease treatment with the modern knowledge that endometriosis involves abdominal cysts.
Group two was given a similar combination, but the bupleurum, cyperus, and tang-kuei was replaced by codonopsis, astragalus, and cimicifuga. These three ingredients treat a condition known as “sinking qi,” secondary to qi deficiency, which often produces symptoms of distended pain in the lower abdomen, and is sometimes manifest as prolapse of the organs. In both of these groups, the formula would be modified further with additions or deletions according to specific symptoms.
The third group received an intravenous drip of salvia extract daily. This rather inconvenient therapy delivers an extract of an herb currently used for normalizing blood circulation. Many patients in China (and several of the doctors) are convinced that IV therapy is more powerful than oral therapy. Intravenous salvia extract is used for several other diseases, notably cardiovascular diseases and hepatitis, both of which involve blood circulation disorders. The individuals in this treatment group would usually also receive some herbs in decoction.
Each of the groups received the treatment for two to three menstrual cycles. 128 of the women (82%) had their symptoms mostly or entirely alleviated, while 28 of the women (18%) had either no effect, or the benefits of the treatment were lost soon after stopping use of the herbs. Considerable laboratory analysis was also done, investigating the condition of the blood contents before and after treatment and in different phases of the menstrual cycle, but while the results were suggestive, not enough of the women were analyzed by these means to draw firm conclusions.
A Chinese review article describing the theory of treating endometriosis was published by workers at this hospital in 1982, and a copy was brought to the U.S. and translated by Dr. C.S. Cheung and his colleagues of the American College of Traditional Chinese Medicine and published in their journal in 1983 (5). Thus, American practitioners were in a position to learn about and apply the treatment of endometriosis by Chinese medicine, which they did without conducting any clinical studies until 1993 (such studies reviewed in a later section).
The article presented two prescriptions from the famous physician Wang Qingren, who during the latter part of the 19th century expounded upon the theory of blood stasis. One of the formulas is called Persica and Achyranthes Combination (Xuefu Zhuyu Tang); it is today used also for headache, chest pain, and numerous other disorders that are believed to have their basis in a stagnation syndrome. The theory of treatment is that qi stagnation (a condition often associated with emotional experiences including anger, depression, and anxiety) occurs first, followed by stagnation of blood (abnormal pattern of circulation, especially within the capillary beds); however, the treatment can also be used when an injury causes blood stasis which does not resolve because of a problem of qi stagnation. The formula contains bupleurum, tang-kuei, and chih-ko to regulate the qi (chih-ko is more often used for central or upper torso stagnation rather than the lower body stagnation treated cyperus), and it contains herbs for promoting the blood circulation, including red peony, cnidium, raw rehmannia, persica, carthamus, and achyranthes, as well as two auxiliary herbs: platycodon and licorice. It is sometimes modified by adding other herbs, and typical additions are bulrush and pteropus for intense abdominal pain, and sparganium and zedoaria for treating lumps. Thus, it is shown how a well-known traditional prescription can be “updated” for the treatment of endometriosis.
Another formula by Wang Qingren is called Cnidium and Bulrush Combination (the Chinese name for the formula, Shaofu Zhuyu Tang, is translated as the decoction for driving out blood stasis from the lower abdomen). It is used when blood stagnation syndrome is caused by a cold syndrome, which is usually induced by weak metabolism and possibly resulting from certain emotional conditions including profound fear, but it may also be caused by environmental factors and diet. The formula contains the spicy herbs dry ginger, fennel, and cinnamon bark for warming up the body, and the blood circulating herbs tang-kuei, red peony, cnidium, bulrush, pteropus, myrrh, and corydalis.
A third formula mentioned in the article is a modification of the prescription called Persica and Red Peony Combination (Taoren Chengqi Tang), which is a formula for treating acute abdominal pain based on the purgative and blood vitalizing herbs rhubarb and persica. This is used for the condition whereby a heat syndrome causes the blood to escape and cause obstruction. The formula contains the blood-vitalizing herbs red peony, moutan, artemisia anomala, salvia, corydalis, and achyranthes, and it also contains chih-shih; these last two herbs aid the downward circulation. The author of this analysis cited a case of treating endometriosis: a woman who had a diagnosis of “nodules on the posterior uterine wall,” was treated with this formula; after three months the woman was relieved of symptoms and became pregnant. No details were given about general success rates for using the formulas. The combination of persica and rhubarb play a prominent role in an endometriosis pill that was developed ten years after this report.
At another site in Shanghai, the Shanghai College of Traditional Chinese Medicine, Dai Deying worked with 30 cases of endometriosis and reported his results in 1982 (6). The basic formula for patients with endometriosis having dysmenorrhea was bupleurum, red peony, moutan, salvia, corydalis, melia, cyperus, saussurea, patrinia, prunella, rubus, oyster shell, bulrush, and pteropus. During the week before menstruation and during menstruation, the corydalis dosage would be increased, and the remainder of the formula would be modified slightly. The basic formula for patients with endometriosis having heavy menstrual bleeding as the main symptom was codonopsis, astragalus, peony, atractylodes, oyster shell, prunella, eclipta, bulrush, agrimony, moutan, salvia, and rehmannia. The formula would also be adjusted somewhat during and after menstruation. The effective rate was given as 80%, almost identical to that claimed (82%) in the earlier study.
Also in Shanghai, workers at the First People’s Hospital and at the Hangkou District Hospital reported on their experience in treating 43 cases of endometriosis (7). There were three formulas: one for dysmenorrhea cases, using Neiyi Fang (endometriosis formula), comprised of tang-kuei, salvia, red peony, cyperus, calamus gum, cyathula (a substitute for achyranthes), cinnamon, pangolin scales, gleditsia, lacca, zedoaria, and sparganium; one for heavy bleeding cases, using tang-kuei, bulrush, achyranthes, salvia, peony, red peony, cyperus, ophicalcite (a mineral), rhubarb, and calamus; and a node-dispersing formula for patients with large cysts, comprised of tang-kuei, salvia, red peony, cyathula, cyperus, cinnamon twig, sargassum, anteater scales, gleditsia spine, calamus, curcuma, and lacca. The formulas were further modified according to specific symptoms that were present. The effective rate was 88%, with four of the women getting pregnant. Despite the good resolution of symptoms and the finding that cysts were reduced in size, there were no cases observed in which the cysts vanished.
A three-step treatment with differing herb formulas before, during, or after menstrual bleeding, was reported in 1983 (8) by workers at the Ruijin Hospital of the Second Medical College of Shanghai. For the week following menstruation, a formula comprised of cinnamon, red peony, moutan, persica, laminaria, epimedium, cynamorium, eupolyphaga, vacarria, and the traditional prescription Xiao Yao San (Bupleurum and Tang-kuei Formula; a qi-regulating formula) was used. Then, for a week during the premenstrual phase, a formula containing bulrush, pteropus, salvia, achyranthes, frankincense, myrrh, sparganium, zedoaria, and artemisia, plus pills made from sanqi (raw tien-chi ginseng) was taken. Finally, during menstruation, bulrush, pteropus, phellodendron, limestone, carbonized cyperus, lindera, cnidium, carbonized rhubarb, astragalus, and cinnamon bark were used for three to five days. As before, the formulas might be varied somewhat according to specific needs. Of 60 patients treated by this method, 29 showed marked improvement, 18 showed some improvement, 11 improved but then relapsed with ceasing the use of herb formulas, and 2 failed to respond. The effective rate was thus 78%. Treatment time varied from 3 to 12 months.
It can be observed from the above initial research work that different formulas are used for different disease manifestations and these are further modified for individual requirements, and the effective rate is in the range of 78–88% (aggregate rate: 82%). The dosage of herbs used, though not specified above, is indicated in the medical journal articles. Most of the herbs in the formulas are given in dosages of 6–15 grams per day (as is standard practice), and the dosage of the entire formulation is typically 150 grams or more. Treatment time is not always specified in the articles, but is usually two to three months. Those who do not respond within that period of time will probably not be helped by these particular formulas, but some patients may need to continue the therapy longer—perhaps a year—in order to maintain the effects.
After this rush of research activity, there was a slight pause in major publications from Shanghai, but other cities began reporting on similar efforts. For example, a report (9) from the Sichuan Medical College in Chengdu (1985) describes treatment of 42 cases of endometriosis. The prescriptions given were varied according to needs, but were made up of warming tonics for kidney deficiency (morinda, epimedium, dipsacus, cuscuta), qi tonics (codonopsis and astragalus), a qi-regulating herb (cyperus), plus blood stasis-removing herbs (moutan, persica, carthamus, bulrush, rubia, red peony, myrrh, and frankincense). The herbs were given as a decoction, taken after menstruation, 15–20 batches (one batch is a one day dose) per menstrual cycle, used for three to six months depending on the development of the case. After that, the herbs might be continued for several months with less frequent use, as needed. Most patients consumed about 100 batches of herbs (thus 5–6 months). With this therapy, 5 patients were said to be cured (with 1 pregnancy), 23 were markedly improved (with 6 pregnant), 11 were somewhat improved, and 3 failed to respond. Thus, about 67% had marked improvement or cure; and 93% showed positive response. After one year, only 3 of the improved cases had recurrence of the original disorder later.
A report (9) from Anhui College of Traditional Chinese Medicine (1988) described the use of a formula that promotes circulation of qi and blood and nourishes blood, Tongjin San, made with tang-kuei, peony, moutan, carthamus, cyperus, curcuma, melia, zedoaria, lindera, corydalis, and cnidium. The herb powder, with modifications as deemed necessary, was decocted and taken a few days after beginning menstruation, continued for seven to ten batches per menstrual cycle. 30 patients were treated for six months following this method: 9 of them were markedly improved (with 4 pregnant), 18 were improved, and 3 showed no effect; thus a 90% effective rate.
Another report (10), this time from the Xiyuan Hospital in Beijing, described the use of Cnidium and Bulrush Combination (Shaofu Zhuyu Tang), modified slightly if necessary to treat the qi stagnation, qi deficiency, or heat accumulation etiologies. Forty patients were treated, of which 25 had the cold type syndrome for which the base formula is designed, 10 had the qi stagnation syndrome, 3 the qi deficiency syndrome, and 2 the heat syndrome. Treatment time ranged from one month to two years, with a total effective rate of 97.5%.
A study (11) at the Zhejiang Medical University was carried out with Chinese herbs differentiated for qi stagnation or qi deficiency type syndrome. In the former case, the combination of salvia, red peony, bulrush, pteropus, tang-kuei, cyperus, sparganium, zedoaria, and corydalis was given; in the latter case, codonopsis and astragalus were added. Of 76 patients treated with herbs (there were an additional 9 cases treated with danazol), 69 had alleviation of menstrual pain (91% effective rate), and among 30 of the cases that had menstrual irregularity, 22 had it normalized. Among 18 cases of pain on intercourse, 9 had relief of that symptom.
In 1989 a lengthy review of endometriosis was published in English, again in the Journal of the American College of Traditional Chinese Medicine (12). The report was compiled by He Xianlin, a physician at the Guangzhou Municipal Hospital. More than two dozen formulas are presented, including some of those already mentioned above, and there are suggestions for acupuncture therapy as well. A comment about treatment worth noting is this: “Although there are many ways to achieve the same goal, one thing is agreed upon by all sources with regard to endometriosis. The major pathology is that of qi and blood stagnation. Both problems will need to be addressed but at the root of it all is the kidney qi deficiency. Attention should also be paid to treatment according to cycle phase and predominance of the most severe symptom (usually dysmenorrhea or excessive uterine bleeding).”
Despite this claim that general agreement had been reached about etiology and treatment, the Chaozhou Hospital issued a report (13) in 1990 on treatment of 30 women with endometriosis, using Shixiao Guijie Tang, composed primarily of bulrush, pteropus, calamus gum, san-chi, and tang-kuei. This formula contains none of the qi-regulating herbs or kidney tonic herbs, but includes only the blood-vitalizing therapies. It was reported that 12 cases were cured, 16 cases showed improvement, and 2 cases did not respond. This treatment had a high “cure” rate (40%) and effective rate (93%).
Along the same lines, a report (14) from the Tianjin College of Traditional Chinese Medicine (1990) referred to treatment using sparganium, zedoaria, melia, red peony, cinnamon twig, hoelen, persica, moutan, corydalis, salvia, gleditsia spine, and prunella during the menstrual cycle except during menstruation, at which time the formula was changed to rubia, pteropus, bulrush, melia, angelica, myrrh, artemisia anomala, corydalis, asarum, and sanqi. Of the 45 patients treated, 38 responded favorably (84% effective rate). Although melia helps treat qi stagnation and cinnamon twig mildly tonifies the kidney, it can not be argued that this formula really addresses those issues.
The combined results of the studies reported during the period 1980–1990 were that the success rate (yielding some degree of improvement) for treatments with herbal decoctions ranged from 78% to 97.5% with an aggregate effective rate of about 86%, close to that found for low dosage gossypol therapy. There were also additional studies not described here, but which had similar therapeutic strategies and a similar level of success.
An English language review of the endometriosis work in China appeared in a report about infertility by Bick Jane Tang, published in 1990, with excerpts published in the International Journal of Oriental Medicine in 1991. A further description of Chinese medical treatment, revolving about a case study, was published in the International Journal of Oriental Medicine in 1992, based on the work done in Shanghai with drug therapy and traditional herbal formulas. One interesting comment in this last paper was that the herb tripterygium had been used in treating endometriosis, with an effective rate of 80% using a three month therapeutic course. This herb functions as an immune-suppressive anti-inflammatory, acting much like prednisone; its success suggests that the autoimmune hypothesis for endometriosis is correct.
A NEW TREATMENT METHOD FROM SHANGHAI
The Shanghai College of Traditional Chinese Medicine affiliated hospital reported (17) in 1991 an apparently successful treatment for endometriosis—Neiyi Wan #1 (endometriosis pill)—comprised of just three herbs, using turtle shell, vinegar-treated rhubarb, and succinum. These materials were powdered, made into pills, and taken in the amount of 2.5 grams each time, twice daily.
This approach differs markedly from those mentioned above, in that very few herbs are used (all of them have the property of vitalizing blood circulation) instead of many, the herbs are in the form of pills rather than decoctions, and the dosage to be taken is very modest.
The initial study involved 76 cases of endometriosis, with 61 “effectively treated,” a rate of 80%, which is comparable to what was claimed with the more complex decoctions. In particular, of 63 patients with prominent pain associated with endometriosis, 89% were relieved. The herb formula was able to “thin the blood” (reducing the abnormally high viscosity and RBC electrophoretic time of the endometriosis patients) and reduce excess populations immunoglobulins, C3 (complement protein), and T8 cells in peripheral blood. The herbs were taken for three months, and could be continued during menstruation. Pharmacological studies have shown that rhubarb and turtle shell inhibit autoimmune responses.
A follow-up study (18) with the same research team was carried out with Nei Yi Wan #1, reported the following year. There were 95 patients; the effective rates were reported according to major symptoms: dysmenorrhea 99%, pelvic pain 88%, coitus pain 90%, irregular menstruation 80%, anal or rectal pain with downbearing 78%.
The formula was later modified to produce Nei Yi Wan #2, comprised of turtle shell, rhubarb, succinum, and defatted persica seed. Persica is a blood vitalizing herb that is also laxative because of its fatty component; together with the rhubarb, the prescription would be too purgative and it is also difficult to make firm pills, so the fat is removed before inclusion. In a trial (19) reported in 1993, the pills were given in a dosage of 3.5 grams each time, twice daily (the extra 1 gram each time compared to the Nei Yi Wan #1 dosage is the added persica). Additional herbs or formulas might be given for treatment of specific symptoms or underlying conditions. In the trial with 37 endometriosis patients, 4 were said to be cured, 26 effectively treated, and only 7 not responding, with a total effective rate of 81%. There was not obvious benefit to adding the persica.
CONTINUING EFFORTS
Despite the successes with and convenience of Nei Yin Wan, work with complex formulas in decoction form continued. In part, this may reflect the discomfort that traditional practitioners have with giving patients a simple formula that is not designed for the patient’s specific underlying syndrome.
An application of the previously-mentioned theory that the underlying cause of endometriosis is a kidney deficiency syndrome, which is then complicated by stagnation of qi and stasis of blood was pursued by Li Xiangyun in Shanghai (20). He used epimedium, curculigo, rehmannia, and dioscorea to tonify the kidney, cyperus to disperse stagnant qi, and a combination of sparganium, zedoaria, millettia, and salvia to treat the blood stasis. Additional herbs could be added for various syndromes, and, in particular, for kidney yang deficiency he would add aconite and cinnamon bark or for kidney yin deficiency add ligustrum and lycium root bark. For severe pain, he would add pteropus, bulrush, myrrh, and frankincense. According to the report, of 74 women so treated, 38 were cured (of which 24 became pregnant), and 33 others had various degrees of relief. Treatment time ranged from three to six months.
Along similar lines, workers at the Xuzhou Medical College (21) gave endometriosis patients a basic formula of aconite, evodia, fennel, dipsacus, dioscorea, tang-kuei, saliva, corydalis, cnidium, and persica. This would be modified for various syndromes, including the use of epimedium and cinnamon bark for kidney yang deficiency, rehmannia and ligustrum for kidney yin deficiency, pteropus and bulrush for pain. Of 54 women treated by this method, 25 were reported cured, and 26 others showed improvement, with a total effective rate of 94% (21)
Despite this apparent vindication of the theory that kidney deficiency syndrome underlies many cases of endometriosis, a report from the Heilongjiang College of Traditional Chinese Medicine affiliated hospital in Harbin in 1992 (22), once again showed that blood-vitalizing herbs were the key ingredient. The study involved 64 patients who were treated with a decoction of salvia, pteropus, sparganium, zedoaria, cyperus, corydalis, and loranthus. Modifications were made as deemed necessary, and treatment was generally continued for two to three menstrual cycles, without interruption. It was reported that 18 were cured (28%), 26 markedly improved, 16 improved, and 4 did not respond. Blood and plasma viscosity levels and red blood cell electrophoretic time were noted to be high in women with endometriosis before treatment compared to normal values, and these were reduced to near normal levels after treatment.
Two recent publications are representative of the ongoing work in Shanghai. In one study (23), 48 patients were treated with a basic formula which was then modified according to one of five differentiated types. The syndromes of qi stagnation with blood stasis and kidney deficiency with blood stasis were the types most often encountered. The basic formula contained 9 grams each of sparganium, zedoaria, leech, and liquidambar, and 12 grams each of anteater scales, sappan wood, eupolyphaga, and prunella. It was reported that 10 patients were cured, 5 markedly effective, and 28 effective. Ten pregnancies occurred among 14 women in the study that had been considered infertile. In the other study (24), 47 patients were treated with 9 grams each of zedoaria, sparganium, persica, cinnamon twig, and turtle shell, 15 grams of prunella, and 6 grams of rhubarb. The formula was modified according to syndromes. Treatment time was one to three months, and effectiveness was 83%, with two of the patients cured. It was demonstrated that the treatment had marked effects on beta-endorphins, which are abnormal in women with endometriosis who have pelvic pain, and which are normalized by the herbal intervention.
Of the 842 women treated in the studies of complex herb formulas cited above which were conducted over a period of about 15 years, the results indicate that only 12% failed to respond to the therapies. The implication of the results to date is that with use of Chinese herb formulas a cure is possible (among the recent papers where a cure was claimed, 32% of women were said to be cured), and a likely impact of the therapy is a reduction in symptoms and an increased chance of pregnancy.
Required treatment times are three to six months, a duration similar to that necessary with gossypol. It is likely that the shorter treatment times are more appropriate for those with less severe endometriosis or shorter term of the disease. Longer treatment times, up to one year, were used in some cases, but this was not the rule.
METHOD OF THERAPY AND DOSAGE
Decoctions are the main form of therapy that has been used with the complex formulas. These usually involve a high dosage of herbs: as indicated in the two most recent reports, decoctions with about 100 grams of herbs per day (including the modifications to the base formulas) are the basic approach. There are fewer herbs and a lower total dosage than in most of the earlier work with decoctions. Pills made from powdered herbs, as reported in three recent studies, seemed to work nearly as well as the decoctions but the decoctions are the method most often utilized. It is not possible to adjust formulas once a prescription has been made into a pill (adjustments are made by adding second formulas or by drinking a tea containing the additional herbs desired). Statements about a “cure” were not made in two of the studies using pills, and the one which reported cures had only an 11% rate, though the reported changes in laboratory parameters were impressive. It is possible that a treatment based on using pills for part of the therapy (perhaps initially for easy administration as a trial approach to get notable symptom relief) and decoctions for another part of the therapy (to prevent recurrence by treating the underlying imbalances) would be most appropriate.
The preferred ingredients for treatment are clearly the blood-vitalizing herbs such as bulrush, pteropus, and corydalis (for pain), zedoaria and sparganium (for resolving masses), salvia, red peony, and cnidium (for normalizing circulation), myrrh, frankincense, and calamus gum (resins used for treating damaged tissues), rhubarb, anteater scales, persica and carthamus (for breaking-up clotted blood), and achyranthes (said to draw blood circulation downward). There is some use of qi-regulating herbs, mainly cyperus, lindera, melia, bupleurum, and curcuma (the latter also counted among the blood-vitalizing herbs). Tonic herbs are given as needed, including the qi tonics astragalus and codonopsis, the blood tonics tang-kuei and peony, and the kidney yang enhancers cinnamon bark, aconite, and fennel.
U.S. TRIALS
As described above, English language information about Chinese medical treatment of endometriosis first appeared in 1983, and there have been reports in journals and books appearing regularly since about 1988. The Institute for Traditional Medicine has mentioned this literature and had received some reports about experience of treating endometriosis patients in the early 1990’s.
According to experience of some American practitioners, it appears that after initiating treatments the first menstrual cycle is sometimes more painful than previous ones (possibly due to incomplete alteration of circulatory patterns), the second menstrual cycle involves discharge of large clots (demonstrating some progress in altering the blood flow), and the third and subsequent cycles begin to show the alleviation of symptoms. The experiences during the first two cycles of treatment tend to be discouraging and may lead to unnecessary changes in therapy or cessation of the method. If such reactions occurred in China, patients would have been strongly encouraged to continue the therapy. It is possible that some of these reactions might be reduced by starting with different formulas than had been used by the American practitioners. Certainly, not all patients experience this sequence of events. A three month period of treatment, however, should be sufficient to demonstrate notable improvements, based on this experience.
Nearly all the herbs described in the Chinese literature are available to Western practitioners. However, lower success rates in treating endometriosis could arise from failure to use adequate dosage or from non-compliance of patients with the long course of taking herbs, especially if they are in the form of decoctions. The Institute for Traditional Medicine (ITM) has been producing several herb formulas in a convenient tablet form, under the name Seven Forests since 1987 for the purpose of carrying out research (25). There are currently 105 formulas in this form. Some of these contain many of the herbs mentioned above in treatment of endometriosis, including Tang-kuei 18, Lindera 15, and Corydalis 5; the latter two formulas were introduced in 1990, and three informal clinical evaluations involving dysmenorrhea have been carried out using them, two of the trials with women diagnosed as having endometriosis, and one with young women complaining of persistent dysmenorrhea.
The two endometriosis studies were organized by Arthur Shattuck, an acupuncturist and herb specialist. In the first study (1992), 17 patients participated, of which 15 completed a course of 16 weeks of therapy; of the two drop-outs, one had become pregnant (a desired outcome) and one was non-compliant with the protocol. All had endometriosis confirmed by laparoscopy, and the age range was 21 to 47 years. The women consumed two herbal formulas, one throughout the menstrual cycle (Lindera 15, a combination of qi-regulating and blood-vitalizing herbs), and one only if pain was noted (Corydalis 5, a combination of blood-vitalizing herbs with pain-alleviating qualities). According to the study report (26), 47% of women who completed 16 weeks of therapy had noted substantial pain relief, and 27% noted slight pain improvement. Of the 11 women who noted pain improvements, 5 also reported improvements in cycle regularity. If one includes the two drop-outs, one with a successful outcome and one with a failed outcome, then it can be said that the total effective rate was 75%. While this is somewhat lower than the Chinese experience, the dosage of the therapy was also quite low. Lindera 15 was taken in the amount of 3 tablets three times per day, with just 6.3 grams of herbs (during pain episodes, Corydalis 5 would be taken in doses of 2–3 tablets per day, thus raising the total dosage to up to 12.6 grams).
Neiyi Wan #1 has been produced in tablet form (Turtle Shell Tablets, Seven Forests) for evaluation in the United States in 1993. Initial reports from ITM’s An Hao Natural Health Care Clinic in Portland, Oregon were favorable. However, the rhubarb component causes intestinal cramping and/or diarrhea in some users, so the formula can not be applied to those suffering from diarrhea or irritable bowel as a chronic problem. Arthur Shattuck initiated a treatment program involving four sites in 1993 (two in Wisconsin and two in Illinois), using the Lindera 15 and Corydalis 5, plus Turtle Shell Tablets in some patients. Improved paperwork for tracking outcomes was developed and the trial was planned to last for six months rather than four months.
He reported (27) that of the 14 clients under care all described a decrease in symptoms during the initial treatment period. However, he found that many people discontinued treatment after getting some relief, so that while the benefits were obvious, the full research project was not completed.
In 1994, Christine Harrison in Denver organized a trial for evaluation of Chinese herbs in the treatment of dysmenorrhea. Patients received Tang-kuei 18 (a blood nourishing and blood vitalizing formula) for two weeks after menstruation and Lindera 15 for the following two weeks. The recommended dosage was 5 tablets each time, three times daily (daily dosage is 10.5 grams of herbs). Patients were treated for 12 weeks and also received acupuncture therapy. The patients were given surveys to evaluate the effects. In the study group of 18 women, 83% reported substantial improvement in pain and 72% reported other health benefits from the herbal treatment (28).
While these initial studies were rather informal in their structure, they revealed that one could conduct such evaluations so long as the treatment time is not too long (12–16 weeks was satisfactory), and the treatment protocol involved tablets (with 9–18 per day), which yields better compliance than decoctions. The outcomes appeared positive. A more formal study can now be readily designed.
REFERENCES
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25. Dharmananda, S, A Bag of Pearls, 1999 Institute for Traditional Medicine, Portland, OR.
26. Shattuck, A, personal communication, 1993.
27. Ibid.
28. Harrison, C, personal communication 1995.