CHINESE HERBAL THERAPY FOR ENDOMETRIOSIS

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

BACKGROUND

Endometriosis is named after the tissues lining the uterus, called the endometrium. The uterine endometrium is shed during each menstrual cycle. Endometriosis develops from endometrial tissue that is in the pelvic cavity outside the uterus. This tissue adheres to various pelvic organs, it responds to the hormones of the menstrual cycle (especially estrogen), and sloughs tissue and blood as does the endometrium of the uterus. However, unlike menstrual bleeding, the blood and displaced cells from these abdominal segments of endometrium have no means of being discharged. This results in layers of fibrous tissue developing from the sloughed material which then form masses that can grow to considerable size. These cyst-like masses are called pseudocysts, which usually appear dark blue to brown (the latter called "chocolate cysts"); the endometrial tissues may appear, instead, as lesions prior to formation of the fibrous surrounding tissue.

The primary symptom of endometriosis is dysmenorrhea (severe pain during menstruation), while additional symptoms that can arise include increased menstrual bleeding, pain during 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). The possibility of having endometriosis is suggested by such symptoms, particularly severe pain during menstruation, but it is confirmed only by laparoscopy, which is the insertion of a small viewing tube into the abdomen. It is common practice to perform laparoscopic surgery (laparotomy) during the diagnostic procedure, thus removing some of the cysts as they come into view, using tiny knives or lasers attached to the viewing tube to release them and aspirators to remove them.

Endometriosis is one of the major causes of dysmenorrhea. This painful symptom of endometriosis often occurs two to three years after initiation of the menstrual period, though sometimes it is delayed for several years 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 abdominal pain between periods (e.g., with bowel movements and/or with intercourse).

A heightened awareness of endometriosis came about largely as the result of an intense interest in treating infertility that developed during the 1980s as more women delayed childbearing into their 30s and were then surprised to have difficulty becoming pregnant. Current estimates are that 30-47% of women suffering from this disorder are infertile and, conversely, that about 30-50% of all infertile women have endometriosis. It is not always clear, however, that endometriosis is the cause of infertility, or was merely diagnosed because infertility was already a concern and possibly due to other causes. Fertility in women begins to decline, on average, starting at age 27, and first diagnosis of endometriosis is often after this age.

Endometriosis sometimes vanishes altogether with a pregnancy, or disappears for a while only to return later; it does fade with menopause. Estrogen replacement therapy for menopause can cause endometrial hyperplasia and restimulate endometrial cysts, but combined therapies with progesterone and its derivatives usually 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 endometriosis to gain recognition among the majority of medical practitioners. During the 1980s, 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. The situation has improved during the past 20 years, though there is often still a delay of a year or more between reports of symptoms and confirming the diagnosis, perhaps in an effort to avoid unnecessary laparoscopic examinations at a time when surgical or hormonal treatments might be put off for a time anyway. Also, some women do not seek diagnosis and treatment for dysmenorrhea until they are older and it has been found to persist or worsen. It is currently estimated that, during their menstrual years (typically from age 13-48), about 14% of the female population have a symptomatic manifestation of endometriosis. The incidence of endometriosis appears to have rapidly increased during the 20th century.

The cause of endometriosis is not known: how does the endometrial tissue get into the pelvic cavity? One concept is that there is a back flow of menstrual blood with endometrial tissue gaining entrance to the abdominal cavity; another is that the bits of endometrium are there at birth. It has been suggested that delayed childbirth is responsible for the rapid rise of this syndrome. Having early and repeated pregnancies, as was the case before the 1950s, would likely halt the growth of any endometrial cysts that were present for whatever reason. The effects of delayed childbirth and having fewer or no children have been noted in other ways, such as being associated causally with the rapid rise in breast cancer during this same time period. Once the first pregnancy has been substantially delayed in a woman who has endometriosis with enlarging cysts, the larger cysts are less likely to shrink after a pregnancy and becoming pregnant itself becomes more difficult. Investigations into other potential contributors have yielded some insights, though few conclusions. Autoimmune processes have been suggested to be involved in the progression of the disease; such autoimmune disorders may have a genetic component.

Drug therapy for endometriosis is often unsatisfactory. Most of the current drug therapy is aimed at altering the estrogen-based hormonal stimulus of the endometrial tissue. Examples are the testosterone derivatives Danazol or methyltestosterone, progesterone and related progestogens (e.g., medroxyprogesterone), or using Buserelin, Goserelin, Lupron, Nefarelin, or other Gn-RH (ganodotropin-releasing hormone) agonists. These usually cause significant side effects, particularly androgenic responses including weight gain and facial and body hair growth. However, there are some reported beneficial effects, such as alleviating sleep disturbances and anxiety-depression. 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 (a year or two) and may cause secondary problems, including persistent abdominal pain due to adhesions that form. 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, though one of the main therapies, gossypol, is not available here and can not be recommended due to its potential for serious adverse reactions and toxicity.

Information about endometriosis, its possible causes, incidence level, diagnosis, symptoms, and treatments is available from the Endometriosis Association, an organization established in 1980 with international headquarters in Milwaukee, Wisconsin via their website (http://www.endometriosisassn.org) and their newsletter (1). The World Congress on Endometriosis is convened at three-year intervals, the latest one (Eighth Congress) was held in San Diego during February 2002.

THE SITUATION IN CHINA

In China, endometriosis is called neiyi, meaning internal lump. Laparoscopy, as needed to detect these lumps, was introduced into China around 1960, and reports about this disease first appeared in the literature soon after that. The incidence of endometriosis in China, like that in the U.S., is reportedly increasing (2). China had adopted a policy of recommending women do not have children until at least age 26, with a maximum of one child per family in most cases, a likely contributor to the increased incidence of the disorder. 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. 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 infertile women it was found that about one-third of them had endometriosis.

Before reviewing the traditional herbal treatments, the intensive investigation into a new herbal drug, gossypol, will be reviewed because the Chinese literature on endometriosis is dominated by reference to this herbal drug. Research into its use for endometriosis began in 1979. 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 THERAPY

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 affecting sperm. It is also used for treating female gynecological disorders such as uterine myoma (fibroid) and menopausal bleeding, and it functions partly via a hormonal mechanism in these cases, with effects similar to the Gn-RH drugs. 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. These hormonal and functional alterations, including amenorrhea, are correlated with the cumulative dose of gossypol ingested, and eventually return to normal. The effect of gossypol on endometrial tissues is not, however, purely a result of the anti-estrogenic action.

The applications of gossypol were discovered after it was found that some men became sterile and that some women experienced 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 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 excessive menstrual bleeding (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 cysts 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.

Aside from amenorrhea, 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. 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).

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 along with 10% potassium citrate (10 ml, thrice daily); treatment time was just 2-3 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; amenorrhea often occurred. Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased; progesterone decreased; while estradiol and prolactin were unaffected.

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. The effects of gossypol have been compared in China to that of Danazol, a drug that has been widely used in the U.S.; the latter is faster acting, but its action is less sustained; Danazol was said to have more side effects (mainly strong androgenic effects) than gossypol. It should be noted that cotton roots had 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 is the use of complex Chinese 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 (typically comprised of a dozen herbs) for endometriosis has been discussed by several Chinese physicians. According to the theories of traditional Chinese medicine, endometriosis is best described by the traditional Chinese category of blood stasis syndrome with formation of abdominal lumps. Blood stasis, a condition where small vessels are not capable of carrying normal blood flow, 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, in turn, are mainly the syndromes of qi stagnation (restricted circulation caused by emotional distress) and coldness (impaired metabolism and circulation), sometimes described as kidney yang deficiency. Therefore, when applying the ideas of traditional Chinese medicine, endometriosis will usually be treated by herbs that vitalize blood circulation as the primary therapy. There may be additional herbs administered to address the underlying and concurrent syndromes (e.g., qi stagnation) or specific symptomatic manifestations (e.g., excessive bleeding), such herbs may be added after the initial therapy to resolve the lumps. The herbs most commonly mentioned in clinical reports on endometriosis are outlined in Table 1.

Table 1. Herbs Frequently Cited in Complex Herb Formulas for Treatment of Endometriosis.

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 that 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 treated for qi stagnation and blood stasis and given a combination of sparganium and zedoaria (used for masses associated with blood stasis); gleditsia spine (for gynecological masses); cyperus, bupleurum, and tang-kuei (for regulating qi circulation); and bulrush (typha), and pteropus (for abdominal pain) in decoction, plus an "endometriosis powder" made with earthworm, tabanus, centipede, and leech (for dredging the stagnated blood). Bulrush and pteropus together represent an ancient two-herb combination called Shixiao San (see Appendix 1) widely used for treating severe abdominal pain; the Chinese name for the combination means the formula for returning the smile.

Group two was given a similar combination, but the qi regulating herbs bupleurum, cyperus, and tang-kuei were replaced by codonopsis, astragalus, and cimicifuga. These three ingredients treat a condition known as "sinking qi," that occurs secondary to qi deficiency, which often produces symptoms of distended pain in the lower abdomen. In both of these groups, the formula would be modified further with additions or deletions according to specific symptoms.

The third group received a daily intravenous drip of salvia extract (the single herb). This rather inconvenient therapy delivers an extract of an herb currently used for normalizing blood circulation. The members of this treatment group would usually also receive some herbs in decoction to address their individual needs.

Each of the groups received the treatment for two to three menstrual cycles. The purpose of having the three groups was not to compare one treatment to another, but to treat the women according to the Chinese style diagnosis of their syndrome. According to the report, 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.

A Chinese review article describing the theory of treating endometriosis was published by workers at this hospital in 1982, and later translated by Dr. C.S. Cheung and his colleagues of the American College of Traditional Chinese Medicine (5). 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, Persica and Achyranthes Combination (Xuefu Zhuyu Tang), is today used for numerous painful disorders, including headache and chest pain (see Appendix 2). 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 herbs for promoting the blood circulation, including red peony, cnidium, raw rehmannia, persica, carthamus, and achyranthes (or cyathula), as well as two auxiliary herbs: platycodon and licorice. It is sometimes modified by adding other herbs, and typical additions are typha and trogopterus for intense abdominal pain, and sparganium and zedoaria for treating lumps.

The other formula by Wang Qingren mentioned in this article is 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 (typha), trogopterus, myrrh, and corydalis (the formula is briefly mentioned in Appendix 2).

A third formula mentioned in the article is a modification of 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 formula is traditionally used for the condition whereby a heat syndrome causes the blood to escape the vessels and cause obstruction. The formula includes the blood vitalizing herbs red peony, moutan, Artemisia anomala, salvia, corydalis, and achyranthes, and it also has chih-shih; these last two herbs aid the downward circulation. The combination of persica and rhubarb play a prominent role in an endometriosis pill that was developed ten years after this initial report, as described in the next section.

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 as the main symptoms was: bupleurum, cyperus, saussurea, and melia for qi stagnation; red peony, moutan, salvia, corydalis, typha, and trogopterus for blood stasis and pain; and patrinia, prunella, and oyster shell for resolving the abdominal masses. During the week before menstruation and during menstruation, the corydalis dosage would be increased (to help alleviate pain), 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, and atractylodes for tonifying qi; peony, moutan, and salvia for circulating blood; oyster shell and prunella for resolving the abdominal masses, and eclipta, fried typha, agrimony, and raw rehmannia for inhibiting bleeding. The formula would also be adjusted somewhat during and after menstruation. The effective rate for treating the symptoms addressed was reported to be 80%.

Workers at the Shanghai First People's Hospital and at the Hangkou District Hospital in Shanghai reported on their experience in treating 43 cases of endometriosis (7). There were three formulas; all of them including qi and blood vitalizing combination of cyperus, tang-kuei, salvia, red peony, and calamus gum. The formula for treating dysmenorrhea as the main symptom also included cyathula, cinnamon, pangolin scales, gleditsia spine, lacca, zedoaria, and sparganium; a similar nodule-dispersing formula was given for patients with large cysts, replacing zedoaria with sargassum and curcuma. The formula for heavy bleeding cases, added fried typha, achyranthes, peony, ophicalcite (a mineral), and rhubarb to the base formula. The herb combinations were further modified according to specific symptoms that were present. The effective rate was reported to be 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, and 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, eupolyphaga, and vacarria for treating blood stasis; laminaria for resolving masses, and epimedium and cynamorium for tonifying yang and warming the abdomen was given along with the traditional prescription Xiao Yao San (Bupleurum and Tang-kuei Formula; a well-known qi regulating formula). Then, for a week during the premenstrual phase, a formula for blood stasis and pain-containing typha, trogopterus, salvia, achyranthes, frankincense, myrrh, sparganium, zedoaria, and artemisia, plus pills made from sanqi (raw tien-chi ginseng)-was taken. Finally, during menstruation, typha, trogopterus, phellodendron, limestone, lindera, cnidium, carbonized cyperus and carbonized rhubarb (the carbonized herbs reduce bleeding), 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 (for showing improvement without relapse soon after) was thus reported to be 78%. Treatment time varied from 3-12 months.

According to these reports from Shanghai, the effect of administering the herbs on a daily basis for 2-3 months is that 78-88% of patients experience relief of common symptoms, such as dysmenorrhea and excessive menstrual bleeding. The dosage of herbs used, as indicated in the medical journal articles, is typically 6-15 grams per day for each ingredient in the formula (as is standard practice), and the dosage of the entire formulation is typically 150 grams or more. This is a large dosage of herbs, and usually requires drinking at least two cups of strong tea per day (normally, the herbs are discontinued only during 3-4 days of menstrual bleeding, after the first day of the period). Some patients may need to continue the therapy longer than a few months-perhaps a year-in order to maintain the effects.

After this rush of research activity in Shanghai, reports from studies in other cities appeared detailing similar efforts. For example, a report (9) from the Sichuan Medical College in Chengdu (1985) described 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, typha, 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 free of symptoms (with 1 pregnancy), 23 were markedly improved (with 6 pregnant), 11 were somewhat improved, and 3 failed to respond. Thus, about 67% had substantial improvement and 93% showed positive responses. 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, 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) described previously, but modified slightly if necessary to treat qi stagnation, qi deficiency, or heat accumulation syndromes. 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 during 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 in the review, 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 syndrome. Attention should also be paid to treatment according to cycle phase and predominance of the most severe symptom (usually dysmenorrhea or excessive uterine bleeding)."

The Chaozhou Hospital issued a report (13) in 1990 on treatment of 30 women with endometriosis, using Shixiao Guijie Tang (a modification of Shixiao San) composed primarily of typha, trogopterus, 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 had symptoms completely alleviated, 16 cases showed improvement, and 2 cases did not respond, with a total effective rate of 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, typha, trogopterus, melia, angelica, myrrh, artemisia anomala, corydalis, asarum, and san-chi. Of the 45 patients treated, 38 responded favorably (84% effective rate).

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 reported level of success. Although numerous formulations were utilized at the different hospitals and for women with slightly different syndromes, the herbs listed in Table 1 appeared repeatedly throughout the reports, indicating a basic agreement in the selection of herbs that would be valuable for endometriosis using complex herb formulas.

A NEW TREATMENT METHOD FROM SHANGHAI: SIMPLIFIED THERAPY

The Shanghai College of Traditional Chinese Medicine affiliated hospital reported (17) in 1991 an apparently successful simplified treatment for endometriosis-Neiyi Wan #1 (endometriosis pill)-comprised of just three herbs: 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 from those mentioned above in that very few herbs are used and the herbs are in the form of pills rather than decoctions, with the dosage to be taken is very modest.

The initial study involved 76 cases of endometriosis, with 61 said to be effectively treated, a success rate of 80%, which is comparable to what was claimed with the more complex decoctions. In particular, of 63 patients with dysmenorrhea as the prominent symptom, 89% were relieved. The herb formula was able to "thin the blood" (reducing the abnormally high viscosity of the endometriosis patients) and reduce excess populations of immunoglobulins, C3 (complement protein), and CD-8 T-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) by the same research team was carried out with Nei Yi Wan #1, and reported the following year. There were 95 patients; the effective rates claimed were: dysmenorrhea 99%, pelvic pain 88%, coitus pain 90%, irregular menstruation 80%, anal or rectal pain with downbearing 78%.

The formula was later slightly modified to produce Nei Yi Wan #2, comprised of turtle shell, rhubarb, succinum, and defatted persica. 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 due to 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 no obvious benefit to adding the persica.

CONTINUING EFFORTS: RETURN TO COMPLEX FORMULAS

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 blood stasis. Additional herbs could be added for various syndromes. 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 trogopterus, typha, 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 Suzhou Medical College (21) gave endometriosis patients a warming 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, and trogopterus and typha 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). This research was followed up at the same hospital (this time in collaboration with a Shanghai Medical University hospital) with a study reported in 1998, comparing an herb formula with Danazol (29). The herb formula included the blood vitalizing herbs sparganium, zedoaria, leech, eupolyphaga, and pangolin scale with kidney yang tonifying herbs, such as cuscuta and epimedium, the decoction (or factory-produced liquid extract) was taken once per day for three months. Danazol was administered in doses of 200 mg each time, three times daily. The relief of dysmenorrhea between the two groups did not differ significantly, but the herbs yielded better results in curing infertility. The herbs were shown to reduce prostaglandin levels, and regulate hormones and immune responses.

Despite this focus on the theory that kidney yang deficiency syndrome with abdominal coldness underlies many cases of endometriosis, a report from the Heilongjiang College of Traditional Chinese Medicine affiliated hospital in Harbin in 1992 (22), showed that blood vitalizing herbs were the key ingredients. The study involved 64 patients who were treated with a decoction of salvia, trogopterus, 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 had all symptoms alleviated (28%), 26 were 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 publications appearing in 1995 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 pangolin scales, sappan, eupolyphaga, and prunella. It was reported that 10 patients were alleviated of all symptoms, 5 markedly improved, and 28 somewhat improved. 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 free of symptoms. 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 900 women treated in the studies of complex herb formulas cited above which were conducted over a period of about 20 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 elimination of symptoms is possible and a likely impact of the therapy is a reduction in symptoms and an increased chance of pregnancy. Overall, required treatment times appear to be three to six months in most cases, a duration similar to that necessary with gossypol and Danazol. 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 even with formulas that have obviously been simplified since the earlier efforts. Pills made from powdered herbs, as reported in three recent studies, seemed to work nearly as well as the decoctions but, even so, the decoctions are the method most often utilized. 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.

U.S. EXPERIENCE

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 U.S. experience of treating endometriosis patients in the early 1990s.

It appears from such reports 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. Not all patients experience this sequence of events, but it is valuable to advise patients of this possibility before they begin therapy. 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. Pangolin scale is on the endangered species list, making it unsuitable for common use (it is not banned from trade, but requires special licensing for import). Success rates lower than those reported in the Chinese medical journals 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 over 150 formulas in this form, prescribed by licensed health professionals. Some of these contain herbs mentioned above for treatment of endometriosis, including Lindera 15 (a formula for regulating qi and blood and alleviating pain), Corydalis 5 (based on Shixiao San with corydalis), Lower Palace Tablets (based on Shaofu Zhuyu Tang), and Turtle Shell Tablets (based on Neiyi Wan #1).

Two small 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 participants 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), and one only if pain was noted (Corydalis 5). 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%, somewhat similar to that claimed in China. 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 was adjusted; half of the formula is the original Neiyi Wan, and the other half is comprised of herbs that are frequently mentioned in the more recent medical reports from China (sparganium, typha, red peony, cinnamon twig, and persica). This change has solved the problem of intestinal reactions, though the formula should still be avoided if a person tends to get intestinal cramping and diarrhea for any reason.

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. The formulas mentioned here are not currently available to the public except by prescription from health professionals.

REFERENCES

1. Endometriosis Association, Newsletter, 1980-present, Endometriosis Association, 8585 N. 76th Place, Milwaukee, WI.
2. Han ML, Treatment of endometriosis with gossypol, in Recent Advances in Chinese Herbal Drugs (Zhou JH and Liu GZ, eds.), 1991 Science Press, Beijing.
3. Chang HM (ed.), Abstracts of Chinese Medicine, 1986-present, Chinese Medicinal Materials Research Centre, Shatin, Hong Kong.
4. Shao GQ, et al., Clinical and experimental research on 156 cases of endometriosis treated by therapy of promoting blood circulation and removing stasis, Shanghai Journal of Traditional Chinese Medicine 1980; 3:4-6
5. Cao LX, Endometriosis as treated by traditional Chinese medicine, Journal of the American College of Traditional Chinese Medicine 1983; 1:54-57
6. Dai DY, 30 cases of endometriosis treated by taking Chinese herbs orally, externally, and by enema, Shanghai College of Traditional Chinese Medicine 1982; 3:34-35.
7. Cai XS, et al., 43 cases of endometriosis treated by differentiation of syndromes, Shanghai Journal of Traditional Chinese Medicine 1982; 4: 12-13
8. Liu DF, et al., A mechanism approach and clinical observation on endometriosis treated by therapy of promoting blood circulation and removing stasis, Chinese Journal of Integrated Traditional and Western Medicine 1983; 3(4): 207-209.
9. Fu Kezhi, personal communication, 1992.
10. Lin YQ, et al., An approach to treatment of endometriosis by traditional Chinese medicine, Fujian Journal of Traditional Chinese Medicine 1988; 19(6): 21-23.
11. Lin YH, et al., Analysis of 85 cases of endometriosis treated by integrating traditional and Western medicine, Zhejiang Journal of Traditional Chinese Medicine 1989; 24(4): 159-160.
12. He XL and Frosolone S, The treatment of endometriosis with traditional Chinese medicine, Journal of the American College of Traditional Chinese Medicine 1989; 7(1-2):31-48.
13. Zhuang B and Xia GC, Correlation between treatment of syndrome differentiation and basic body temperature in 21 cases of endometriosis, Shanxi Journal of Traditional Chinese Medicine 1990; 11(12): 537.
14. Jin JL, 45 cases of endometriosis treated by blood circulation promoting and stasis removing therapy and laboratory analysis for nail-fold microcirculation, Shanxi Journal of Traditional Chinese Medicine, 1990; 11(9): 402-403.
15. Tang BJ, Traditional Chinese herbal and acupuncture treatment for female infertility (part II), International Journal of Oriental Medicine 1991; 16(3): 151-161.
16. Jin YC, Teaching rounds: endometriosis, International Journal of Oriental Medicine 1992; 17(4): 1206-210.
17. Wang DZ, Wang ZQ and Zhang ZF, Study on the treatment of endometriosis with removing blood-stasis and purgation method, Chinese Journal of Integrated Traditional and Western Medicine 1991; 11(9): 524-526.
18. Wang ZQ, Zhang ZF, and Wang DZ, Clinical and experimental studies of stasis-reducing and viscus-opening therapy for endometriosis, Shanghai Journal of Traditional Chinese Medicine 1992; 9: 8-12.
19. Yu CQ, Influence of Nei Yi Wan #2 on levels of beta-EP and DynA in endometriosis, Chinese Journal of Integrated Traditional and Western Medicine 1993; 13(1): 7-9.
20. Li XY, Method of kidney tonifying and stasis removing for 74 cases of endometriosis, Shanghai Journal of Traditional Chinese Medicine, 1991; 7:20-21.
21. Jiang JN, et al., Clinical observation of 64 cases of endometriosis treated by blood vitalizing and stagnation-eliminating therapy, ACTA Chinese Medicine and Pharmacology 1992; 1:38-39.
22. Qu JZ and Liu GZ, Wen Hua Yin combined with ear-pressing therapy for the treatment of 54 cases of endometriosis, Shanxi Journal of Traditional Chinese Medicine 1992; 13 (5): 198-199.
23. Hu GZ and Li XY, 48 endometriosis patients treated by the principle of eliminating stagnation and activating blood circulation, Shanghai Journal of Traditional Chinese Medicine 1995; 2: 38-40.
24. Yu CQ, Effect of Nei Yi Fang on plasma endorphin levels during the menstrual cycle in women with endometriosis, Chinese Journal of Integrated Traditional and Western Medicine, 1995; 15(1): 6-8.
25. Dharmananda, S, A Bag of Pearls, 2002 Institute for Traditional Medicine, Portland, OR.
26. Shattuck, A, personal communication, 1993.
27. Ibid.
28. Harrison, C, personal communication 1995.
29. Liu Jian, Li Xiangyun, and Hu Xiaomei, Clinical observation on patients with endometriosis treated by tonifying kidney and removing blood stasis, Chinese Journal of Integrated Traditional and Western Medicine, 1998; 4(3): 166-169.
30. Bensky D and Barolet R, Chinese Herbal Medicine: Formulas and Strategies, 1990, Eastland Press, Seattle, WA.
31. Hsu HY, et al., Oriental Materia Medica: A Concise Guide, 1986 Oriental Healing Arts Institute, Long Beach, CA.
32. Jia Kun, Treatment and Prevention of Carcinoma with Traditional Chinese Medicine, 1985, Commerical Press, Hong Kong.
33. Xu Xiangcai (chief editor), English-Chinese Encyclopedia of Practical Traditional Medicine (volume 4: Simple and Proved Remedies), 1990 Higher Education Press, Beijing.
34. Wang Qi and Dong Zhilin, Modern Clinical Necessities for Traditional Chinese Medicine, 1990 China Ocean Press, Beijing.
35. Wong KC and Wu LT, History of Chinese Medicine, 1973 AMS Press, Inc., New York.
36. Huang Bingshan and Wang Yuxia, Thousand Formulas and Thousand Herbs of Traditional Chinese Medicine, vol. 2, 1993 Heilongjiang Education Press, Harbin.
37. Yan Jingxi and Pan Guodong, Review of pharmacology studies and applications of Xuefu Zhuyu Tang, Journal of the Shandong College of Traditional Chinese Medicine 1993; 17(6): 423-425.
38. State Administration of Traditional Chinese Medicine, Advanced Textbook on Traditional Chinese Medicine and Pharmacology, (vol. 2) 1995-6 New World Press, Beijing.
39. Yang Yifan, Chinese Herbal Medicines: Comparisons and Characteristics, 2002 Churchill Livingstone, London.

APPENDIX 1: Shixiao San

Shixiao San is a formula of the Taiping Huimin Hejiju Fang, a famous formulary of the Song Dynasty. It is one of the simplest of formulas, comprised of just two ingredients in equal amounts, ground to powder, to be swallowed down with water mixed with a little vinegar. It is indicated for blood stasis syndrome that causes pain. The formula name literally means the powder for the lost smile, but has been translated also to describe the effect of taking the formula, namely as the "sudden smile powder." In the book Chinese Herbal Medicine Formulas and Strategies (30) it is depicted this way:

Before taking this formula, the patient for whom it is indicated has pain so severe that it is difficult to tolerate. After taking the formula, the pain disappears so fast that it brings a sudden smile to the face.

As relayed further in Formulas and Strategies, the Hejiju Fang indicates that the formula is for post-partum pain that is so severe that the patient wants to die; that other medicines are ineffective, but this one is rapidly effective. Later generations of traditional doctors have extended its use to other painful conditions related to blood stasis, most recently for treatment of angina pectoris and its causes in vascular blockage and arterial spasm.

One of the ingredients of Shixiao San is puhuang, the pollen from the well-known plant called cattail because of its long, round shoot that is about the width of a cat's tail. This plant is a marsh plant with a hollow stem, similar to a rush, and often referred to as the bulrush. The Chinese name for plants of this nature is pu; the pollen is bright yellow (huang), yielding the Chinese name puhuang. The botanical names of the main plant sources are Typha latifolia and Typha angustifolia, so the common name given for it is typha or bulrush. Little is known about it chemical constituents and pharmacology, other than the fact that it is rich in flavonoids, a group of compounds that have been associated with improving blood circulation.

The other ingredient of Shixiao San is wulingzhi, which is the dung collected mainly from Trogopterus xanthipes (flying squirrels), but also from Pteropus pselaphon (known as flying foxes, which are, actually, fruit bats). These are rare species of cave dwelling rodents. Little is known about the active constituents of this material or how they might act to aid blood circulation or relieve pain. The Chinese name refers to the "grease of the spirit of the five elements (31)." This mysterious reference may be to its use as a topical application, perhaps in ointment form (grease), for treatment of skin diseases; the dung has antibacterial properties. According to Li Shizhen (who wrote the Bencao Gangmu and described this substance in his book that was published in 1596) that the substance is affected by the spirit of the five elements. To improve its blood vitalizing properties, it is usually prepared by frying with vinegar.

Wulingzhi has been included in a number of anticancer formulas, because of its implied ability to resolve blood-stasis masses. According to Jia Kun, in his book Treatment and Prevention of Carcinoma with Traditional Chinese Medicine (32), wulingzhi is bitter, sour, pungent, and sweet, with moderate nature, and no toxicity. It is indicated for amenorrhea, menorrhagia, dysmenorrhea, and pain caused by stagnation and obstruction. It relaxes spasms of the smooth muscles, as indicated by laboratory animal studies.

It has become a common practice to combine one or both of the herbs from this traditional formula with corydalis (yanhusuo) and/or salvia (danshen) to improve the blood vitalizing and pain relieving effects. In the English-Chinese Encyclopedia of Practical Traditional Medicine (33), a formula for dysmenorrhea is presented, in which 9 grams each of trogopterus and typha are combined with 30 grams of salvia for a one day dose (taken all at once). The recommended use is for five days administration prior to each menstrual period.

A simple formula for treating abdominal pain due to blood stasis, Shounian San, relayed in Danxi Xinfa (Teachings of Danxi, published in 1481) combined equal amounts of trogopterus, corydalis, myrrh, and caoguo, a type of cardamon (30). In the book Modern Clinical Necessities for Traditional Chinese Medicine (34) two highly effective prescriptions used in clinical trials for treatment of dysmenorrhea are described: the Dysmenorrhea Powder, comprised of trogopterus, salvia, corydalis, sparganium, zedoaria, carthamus, cinnamon, saussurea, and tang-kuei and the Notoginseng Powder for Dysmenorrhea, comprised of typha, trogopterus, corydalis, notoginseng (sanqi), cnidium, fennel, saussurea, and borneol (the main active component of cardamon).

It should be noted that when puhuang is fried and carbonized, it helps stop bleeding, a property commonly found with carbonized herb materials; trogopterus may be prepared similarly to stop bleeding. In these formulas for pain, the cattail pollen and the trogopterus dung are not carbonized. When preparing typha and trogopterus in decoction form, the materials are put into a cloth bag; this is because they degenerate upon cooking and the dregs are hard to filter out afterward.

APPENDIX 2: Xuefu Zhuyu Tang and Shaofu Zhuyu Tang for Treating Blood Stasis

Xuefu Zhuyu Tang is a widely used formula in China designed by the medical reformer Wang Qingren (1768-1831). Wang's interest was in the correct description of the internal organs (zangfu). Chinese physicians had avoided detailed investigation of the body during the previous centuries due to proscriptions against performing autopsies (and public refusal to allow dead bodies of their relatives to be dissected) and limitations on performing internal surgery. Instead, physicians and scholars had relied upon ancient drawings of the internal organs, derived from a small number of investigations before these restrictions came to force.

Those anatomical drawings were crude, and had become a mere illustration to accompany descriptions of organ function that had been derived from theoretical considerations and a variety of observations of patients viewed from the outside. During the Song Dynasty, some new and superior drawings were made after physicians and artists were ordered to dissect and report on the internal organs of some captured bandits. But it was not until Wang Qingren published a small work of two volumes called Yilin Gaicao (Correction of Medical Errors; 1850) that Chinese anatomical studies revived. Soon after, many Chinese doctors adopted the modern anatomical texts, already highly advanced, introduced by Western physicians.

It has been suggested by his contemporaries that Wang's work on anatomy had a number of errors, including observations that led to his formulation of Xuefu Zhuyu Tang. Some of his errors were considered worse than the ones he was trying to correct, so that critical commentators said: "the more Wang corrects, the more errors are made." One of the problems he encountered was the ancient Chinese correlation between blood vessels and the acupuncture meridians. The Chinese had nearly always described the flow of qi and blood as a unitary function, and had not made any distinction between the blood vessels and the acupuncture meridians that were being mapped for Chinese medical purposes. However, the meridian maps that had evolved centuries earlier did not closely follow the actual blood vessels, so that when Wang saw where the vessels actually ran, he was particularly distressed at the discrepancy.

Wang had condemned those who wrote about physiology based merely on guesswork-without direct observation of the body-thus raising a complaint that is scientific in nature: conclusions must be drawn from careful investigation, not simple application of dogma. He commented (35):

To write a book without knowing thoroughly the internal organs, is it not comparable to a man speaking in a dream? To treat a disease without knowing thoroughly the internal organs, how does it differ from a blind man groping in the dark?

Based on Wang's analysis, it has been suggested that upon carrying out his investigations of dead bodies he observed that blood was often found pooled in the chest cavity. He considered that blood stasis in the chest cavity must have been associated with disease. Modern doctors recognize that this pooling of blood most likely occurred because of changes at death, rather than having anything to do with disease.

Nonetheless, Wang designed his formula to treat blood stasis in the chest, which was designated as the "blood palace" (xue = blood; fu = residence of an official, translated as palace or mansion). The formula is comprised of two parts, one to regulate qi circulation and the other to vitalize blood. For regulating qi, he used a modification of the ancient Sini San, comprised of four herbs: bupleurum, peony, chih-shih, and licorice. Since blood vitalizing was to be an important component of therapy, he substituted red peony for peony. He also replaced chih-shih (zhishi) with chih-ko (zhiqiao). Chih-shih and chih-ko have similar properties and functions; they are the immature and mature fruit, respectively, of a type of orange. However, one difference between them has been described as their direction of action. Chih-shih is used to drain downward, thus having a vertical action. It is commonly used in formulas for treating constipation. Chih-ko has a more limited downbearing effect, but is considered valuable for spreading the qi around the central region, and is thus said to have a horizontal action; it is commonly used for problems of the stomach and lungs, and Wang used it to smooth the flow of qi in the chest. Both chih-shih and chih-ko have the shared function of preventing adverse upward rushing of qi that can cause stuffiness in the chest, which is of relevance to this formula. Wang added platycodon to this portion of the formula as an herb to direct the action of all the herbs to the chest. In particular, the combination of bupleurum, which opens the upward flow of liver qi through the liver meridian passing though the sides of the chest, and platycodon, which opens the lung qi, are considered a highly focused pair for relieving stagnation in the chest area.

For the blood vitalizing portion, he selected Persica and Carthamus Combination (Tao Hong Siwu Tang), which is simply Siwu Tang (Tang-kuei Four Combination; tang-kuei, peony, cnidium, rehmannia) plus persica (taoren) and carthamus (honghua). Peony is again mentioned here, with red peony included as above. In addition, the blood vitalizing herb achyranthes, or as specified in many modern texts, the substitute herb cyathula, was added. Cyathula (chuanniuxi) is considered to be a type of achyranthes (huainiuxi); it helps drain the excess blood from the upper body to the lower body. In particular, achyranthes or cyathula with chih-ko helps prevent upward rushing of qi and blood that might result in congestion and accumulation. The formula is (36):

Its function is "to promote blood circulation and remove stasis, as well as activate the flow of qi and relieve pain." Its primary indications are headache and chest pain due to blood stasis or poor blood circulation. The chest pain is attributed to such things as coronary heart disease, rheumatic heart disease, and injury to the chest; the headaches are attributed to concussion as well as any circulation disorder. Because of its regulatory effects on the flow of qi, the formula is also recommended for persistent hiccough.

Xuefu Zhuyu Tang, regardless of its potentially flawed basis in physiology, turned out to be highly effective. It is today employed routinely in the treatment of a number of diseases and injuries and is frequently mentioned in medical journals. In a review article on its pharmacology and applications, the following effects were among those listed (37):

Pharmacology:

• promotes capillary microcirculation
• increases tissue perfusion
• inhibits platelet aggregation
• enhances immune functions
• lowers serum triglyceride and LDL

Clinical Applications:

• coronary heart disease, hypertension, arrhythmia, heart failure, cor pulmonale, rheumatic heart disease
• silicosis, asthma
• liver cirrhosis, chronic hepatitis, and primary liver cancer
• chronic gastritis, duodenal ulcer
• migraine, trigeminal neuralgia, headache in children
• epilepsy, schizophrenia, refractory insomnia, head injury
• polyarteritis nodosa, thromboangitis obliterans, subcutaneous hematoma
• infertility due to fallopian tube obstruction, menopausal syndrome, menorrhalgia
• urticaria, post-herpetic neuralgia

Many of these conditions do not involve the chest or upper body. Chinese doctors have come to view the formula as one that is generally suitable for blood stasis syndromes. One of the benefits of this formula, according to the Advanced Textbook of Traditional Chinese Medicine and Pharmacology (38) is that it "removes blood stasis without consuming blood, and releases stagnant liver qi without consuming qi." This comment refers to the fact that the formula is potent, but still does not cause adverse effects. Normally, there is a concern that strong blood vitalizing formulas and strong qi regulating formulas will cause some damage (consume the blood and qi), thus limiting the duration of their use and restricting their use to persons of strong constitution.

SHAOFU ZHUYU TANG AND GEXIA ZHUYU TANG

Wang Qingren also produced two blood vitalizing formulas for the lower body that are still widely used today. One is called Shaofu Zhuyu Tang (shaofu here refers to the lower palace) and the other is called Gexia Zhuyu Tang (ge = diaphragm, xia = below). The two formulas are similar:

Shaofu Zhuyu Tang		Gexia Zhuyu Tang
Pteropus	9 g		Pteropus	9 g
Bulrush	9 g		Carthamus & Persica	9 g
Corydalis	3 g		Corydalis	3 g
Tang-keui	9 g		Tang-kuei	9 g
Red peony	6 g		Red peony	6 g
Cnidium	3 g		Cnidium	3 g
Cinnamon bark	3 g		Moutan	6 g
Dry ginger	3 g		Lindera	6 g
Fennel	1.5 g		Cyperus	3 g
Chih-ko	5 g
Licorice	9 g

Five of the herbs used for vitalizing blood circulation in each of the formulas match exactly, and in Gexia Zhuyu Tang, the blood vitalizing combination of carthamus and persica simply replaces bulrush in Shaofu Zhuyu Tang. The major differences between these two prescriptions are that Shaofu Zhuyu Tang includes the kidney-warming trio of cinnamon bark, dry ginger, and fennel, while Gexia Zhuyu Tang has the qi regulating trio of cyperus, lindera, and chih-ko. Both are indicated for abdominal pain due to blood stasis. Shaofu Zhuyu Tang would be selected for stasis due to cold (cold-caused congealing of blood) and Gexia Zhuyu Tang would be selected for blood stasis associated with qi stagnation.

An herb common to all these formulas by Wang Qingren is cnidium (chuanxiong). This herb is described at length in the book Chinese Herbal Medicines: Comparisons and Characteristics (39), and the explanation reveals the herb's suitability for these formulas:

Chuanxiong is pungent and warm, and enters the liver, gallbladder, and pericardium meridians. Pungency can disperse congealed blood and warmth can activate the blood circulation and dissipate the obstruction. Chuanxiong is a very effective herb for invigorating the blood and promoting its circulation. It is characterized by high moving speed and strength. It moves upwards, downwards, inwards, and outwards, and can reach every part of the body, so it is regarded as 'the herb that moves qi and blood.'

In clinical practice, it is often used to remove congealed blood and stop pain. It is particularly effective in the treatment of headache when the pain is in the sides of the head, such as in headache caused by stress or migraine. It is also used to relieve pain in intercostal neuralgia, coronary heart disease, and stenocardia, trauma, and arthritis. Since it can reach any part of the body, it can be used to treat cold and cramping pain of the fingers and toes, dysmenorrhea, amenorrhea, and irregular menstruation, which are caused by qi and blood stagnation complicated by cold. Combined with other herbs, it can be prescribed for excess, for deficiency, for cold, or for heat syndromes.