PATHOPHYSIOLOGY

Myoma risk is inversely related to increasing parity and age at last pregnancy, and is decreased by smoking (due to its inhibition of estrogen) and increased by obesity (likely due to increased estrogen levels) and hypertension. 1 2 3^,10 Fibroids occur in 1% to 2% of pregnancies. However, it is uncertain whether this relationship is entirely causal. Infertility, as well as early pregnancy loss, may be due to mechanical obstruction of implantation or distortion of the cervix or endometrium. Once a pregnancy is established, it is rare for myomata to interfere with its progress, and most proceed uncomplicated. However, a higher rate of cesarean section has been noted, and premature labor may result from very large myomata.¹ Degeneration of fibroids, caused by hemorrhagic infarction, may rarely occur during late pregnancy and is marked by pain, and also may be accompanied by rebound tenderness, fever, nausea, vomiting, and leukocytosis.³ Treatment consists of rest and analgesia; surgery is a last resort.

Anemia and fatigue can be caused by excessive blood loss associated with fibroids. Pressure on the bowel or bladder can cause constipation, urinary frequency, and dyspareunia. Large fibroids may mask the diagnosis of serious gynecologic neoplasm. Rapidly growing fibroids may indicate a more serious pathology such as leiosarcoma and should be investigated. Malignancy is rarely associated with uterine fibroids; however, they occur with increased frequency in endometrial hyperplasia and are associated with a fourfold increased risk of developing endometrial cancer.¹

SYMPTOMS

Most women with myomas are asymptomatic, never knowing that they have them unless informed of such by gynecologic examination. This was actually discovered based on ultrasound and autopsy results revealing that many more women had fibroids than had ever been diagnosed or treated for symptoms.² The most common symptoms are menorrhagia and the physical effects caused by large myomata such as increased pelvic pressure, frequent urination, difficulty with defecation, and dyspareunia with deep penetration.^1,3,5 Abnormal uterine bleeding is present in about 30% of all patients, and periods are typically heavy and prolonged, often with premenstrual and postmenstrual spotting.^2,4 Uterine bleeding caused by myomas can be associated with significant social, emotional, financial, and medical difficulties; women’s concerns should be addressed. Some women experience dysmenorrhea.² Metrorrhagia, may occur, but should be evaluated with an endometrial biopsy to rule out other endometrial disease.⁴ About 2% to 10% of women experience infertility as a result of fibroids, ostensibly due to abnormal uterine of tubal motility, interference with sperm movements, or abnormal uterine blood flow.^3,11 Fibroid degeneration, torsion, or compression of a nerve against the pelvis caused by encroachment by a fibroid can lead to significant pain.^4,11

CONVENTIONAL TREATMENT

Unless fibroids are symptomatic, observation is the most prudent form of treatment and no other intervention is necessary.^1,4 GnRH agonists (e.g., Leuprolide) have been used effectively to control symptoms and reduce myoma size through suppression of estrogen and progesterone production.^3,12 Mean uterine size decreases 30% to 64% after 3 to 6 months of treatment, and symptoms associated with fibroids are alleviated as a result. Possible side effects include hot flashes, headache, vaginal dryness and vaginitis, decreased libido, joint and muscle stiffness, and depression, and 30% of patients continue to have light, irregular vaginal bleeding.^3,12 Local allergic reaction occurs in about 10% of patients.³ Bone loss occurs but is reversible, and a small number of women (2%) experience major vaginal hemorrhage 5 to 10 weeks after treatment commences. Steroid add-back therapy has been investigated to prevent bone loss in women requiring long-term GnRH therapy; however, because of the risk of osteoporosis, long-term therapy is inadvisable.^3,12

Surgery should be reserved for women who are past childbearing, who are heavily symptomatic and not responsive to drug therapy, or who have suspected malignancies. Women wanting to preserve childbearing ability should be given the option of conservative therapy. GnRH therapy may be prescribed as pretreatment for surgical procedures to reduce fibroid size and bleeding. Myomectomy may be performed vaginally, hysteroscopically, or laparoscopically, and when performed skillfully, improves symptoms in 80% to 90% of patients. Between 15% and 30% experience fibroid regrowth after 5 years. Uterine scarring may occur from the procedure and affect fertility.¹² Endometrial ablation and uterine artery embolization (UAE) are additional options.^13,14 UAE is increasingly popular, and appears generally safe, but it is uncertain how long the treatment lasts and whether future fertility may be affected. The procedure involves injection of polyvinyl or gelatin particles into the uterine arteries to cut off blood supply to the fibroids, which leads to shrinkage over the next 3 to 12 months. Approximately 85% of patients gain relief from the procedure, which has been performed since 1995. However, it is not risk free. Adverse outcomes include infection, bleeding, and formation of emboli, as well as future fertility problems. For women intending to become pregnant in the future, myomectomy may still be the most certain conventional surgical intervention.¹⁴ Hysterectomy is generally recommended when women are past childbearing age, are symptomatic, malignancy is suspected, or if other therapies are ineffective.^1,3,12

BOTANICAL TREATMENT

Among Western herbalists specializing in gynecologic complaints, there is a common perception that although symptoms of uterine fibroids are not difficult to control with botanical medicines, and their growth can be arrested, they are difficult to eliminate entirely unless the fibroid is small at the onset of treatment (smaller than 12-week size). Many women are content to have symptom control over pharmaceutical or surgical intervention, as long as the fibroids present no mechanical problems.¹⁵ Traditional Chinese medicine (TCM) has clearly defined diagnostic constructs, many herbal formulae, and well-developed adjunctive treatment protocols (e.g., acupuncture, moxibustion) for treating uterine fibroids and has claimed success in entirely eliminating uterine fibroids.

Western herbal treatment protocols include a variety of strategies (Table 7-1). These include weight reduction, promoting hormonal balance, specifically through the elimination of estrogens by enhancing liver detoxification mechanisms, promoting pelvic circulation while simultaneously controlling bleeding if necessary, and general improvement of uterine tone. These are integrated with the general recommendation to avoid excess exposure to xenoestrogens (environmental estrogens) and reduce overall estrogen levels, exposure to both being a risk factor for the development of uterine fibroids. Women with fibroids report greater frequency of red meat and pork intake, and less frequent green vegetable, fruit, and fish consumption.⁴ Although there is little correlation between the development of uterine fibroids and cancer, numerous studies have demonstrated a connection between diet, estrogen levels, and hormone-dependent cancers, as well as a protective effect of fruit and vegetables against cancer.⁴ No studies have evaluated the effects of US dairy consumption and the development of uterine fibroids. However, an association between dairy intake and increased risk of ovarian cancer has been reported.^16,17 Herbalists recommend that patients avoid foods that increase risk, and emphasize intake of those shown to facilitate estrogen biotransformation, for example, by increasing dietary fiber, and regular intake of complex carbohydrates as found in vegetables and grains.^11,18,19 Botanical strategies are aimed at reducing the estrogen burden through liver detoxification and improved elimination, promoting gynecologic health in general by improving pelvic circulation, reducing symptoms, and controlling fibroid size.

TCM treatment for fibroids has been evaluated through several preliminary studies, which are presented in the following section. Western botanical protocol for the treatment of uterine fibroids has not been subjected to controlled trials.⁴ The Western botanical information presented in this chapter reflects the opinions of herbalists practicing in the United States, United Kingdom, Canada, Australia, and New Zealand, regarding the efficacy and safety of the primary herbs used to treat myomas. Given the general safety of the botanicals being discussed, and the lack of noninvasive long-term effective medical treatments for fibroids, it seems that investigation of the primary Western herbal protocols cited in Table 7-1 is warranted. Nervines, laxatives, adaptogens, and other herbs included in fibroid protocol are discussed elsewhere throughout this text. Stress reduction should not be overlooked as part of the treatment protocol for women with symptomatic fibroids, as chronic uterine bleeding can cause emotional, social, financial, and medical consequences.²

NUTRITIONAL CONSIDERATIONS

ADDITIONAL THERAPIES

Exercise not only encourages weight reduction but also improves pelvic circulation, promotes uterine muscular tone, promotes regular bowel elimination, and reduces

stress. Herbalists often recommend specific yoga postures or Kegel exercises to assist in improving pelvic circulation particularly.³⁵ Vigorous walking, hip circling, pelvic thrusts, and belly dancing can all be useful to improve pelvic circulation.

TREATMENT SUMMARY: UTERINE FIBROIDS

PATHOPHYSIOLOGY

Fibrocystic breast changes are an exaggerated response to cyclic ovarian hormones.³⁹ The etiology of fibroadenomas and cyclic mastalgia may also be hormonal, though in some cases, the cause of a fibroadenoma may be unclear. When this occurs in women over 30, removal of the mass is generally recommended.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

There are two primary aims when arriving at a diagnosis of fibrocystic breasts. The first is to rule out breast cancer, and the second is to determine if benign breast symptoms warrant treatment. A careful history, physical exam, and cancer risk assessment are indicated (Box 7-1 and Table 7-2).³⁶ A thorough breast exam is best performed after the menses, as examination prior to menses (when the pain is actually likely to be most acute) can obscure problematic lumps caused by normal breast tissue proliferation and nodularity from normal hormonal changes. If a suspicion of breast cancer remains after the history and physical, further diagnostic tests should be performed as appropriate.³⁶ Diagnosis of fibrocystic breasts can be made on the basis of cancer exclusion. For women experiencing symptoms including pain, tenderness, swelling, inflammation, or nipple discharge, the comprehensive history and physical can be used to determine if the problem is cyclic or noncyclic in nature and whether it is associated with other signs and symptoms, including fever or premenstrual mood swings. It is also important to gently move aside the breast tissue and examine the chest wall and muscle to determine whether breast pain or muscle pain is the proper diagnosis.⁴⁰ Depending on the associated signs and symptoms, a diagnosis, including breast infection, muscle sprain/strain, premenstrual syndrome, or noncyclic mastalgia can be determined.

TABLE 7-2 Risk for Development of Breast Cancer by Type of Benign Breast Disease

Chaste Berry

Chaste berry is extensively recommended by herbal practitioners for cyclic breast pain and fibrocystic breasts, both when it presents independently and when associated with PMS. This traditional use is supported by clinical trials. Chaste berry may be used singly or in combination with other herbs that enhance hormonal regulation and hormone metabolism (e.g., herbs that promote liver function and hormonal conjugation and elimination). There have been three placebo-controlled, double-blind, randomized clinical trials (RCT) examining the effects and safety of a proprietary chaste berry extract–containing solution (VAC) on cyclic mastalgia. VAC is sold as Mastodynon®, and manufactured by Bionorica Arzneimittel GmbH (Neumark/Opf. Germany).⁴¹ It contains 32.4 mg of chaste berry fruit extract/60 drops as well as a mixture of homeopathic ingredients, including Caulophyllum thalictroides, Cyclamen, Ignatia, Iris, and Lilium. This product is available as both a tablet (MR 1025 E1) and a liquid extract in Germany. German drug indications for the product include menstrual disorders based on a temporary or permanent corpus luteum insufficiency, infertility resulting from corpus luteum insufficiency, and menstrually related complaints, including mastodynia.⁴² All three of the studies used the liquid solution, which contained 53% (v/v) alcohol, although the study by Wuttke et al. also used the tablets.^41,43 All three studies defined cyclic mastalgia as having at least 5 days of breast pain the previous cycle and treated women for three menstrual cycles with 30 drops two times daily of VAC (1.8 mL/equivalent to 32.4 mg extract of chaste berry drug). Researchers found that both the severity (assessed on a 1- to 100-mm visual analog scale [VAS]) and presence of breast pain (as measured by women’s diaries) were significantly improved in the women who were assigned to the chaste berry groups compared with placebo after the first month of treatment. Although pain intensity was reduced by 30% in the chaste berry group compared with 11% in placebo after one cycle, pain intensity was even more reduced at the end of the second month of treatment, with 53% of women receiving chaste berry having decreased severity of breast pain compared with 25% of the placebo group (p = 0.006).⁴¹ No further improvement was obtained with longer treatment periods. However, to reduce the number of days with severe pain women needed to receive VECS for three to four cycles before they had significantly fewer days with breast pain compared with the placebo group (p = 0.21).^41,44 Two of the studies also measured serum hormone levels including estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and basal prolactin levels at baseline and in the premenstrual weeks of cycles 1, 2, and 3.^43,45 One study found a significant rise in prolactin levels and a decrease in progesterone levels,⁴⁵ whereas another study found no effect on FSH, LH, and progesterone, but did see a decrease in estradiol levels and a significant decrease in basal prolactin levels (3.7 ng/mL tablets and 4.35 ng/mL liquid extracts) compared with placebo.⁴³ Adverse events were rare and did not differ from placebo in any of the RCTs.

Dong Quai and Blue Cohosh

Along with chaste berry, dong quai and blue cohosh are commonly employed by herbal clinicians to modulate hormone levels. Blue cohosh, as part of the German herbal formulation Mastodyn® (reviewed in the preceding), may provide some of the therapeutic benefit of that formulation. However, to date, no studies have demonstrated that blue cohosh has any effect on hormonal levels. Dong quai in vitro can weakly bind to estrogenic receptors and induce progesterone receptors. However, it did not stimulate vaginal cells or increase endometrial thickness and had no estrogenic effect showing no transactivation of either alpha- or beta-estrogen receptors.^27,46,47 Additionally, dong quai showed no significant effect on either hormonal levels or symptoms in an RCT in menopausal women.^48,49 Consequently, dong quai appears to have a limited if any effect on hormone levels. In a recent study, dong quai was found to have significant anti-inflammatory effects because of one of its constituents, ferulic acid.⁵⁰ Although this study is very preliminary, it may offer an alternative mechanism through which dong quai could be helping to decrease mastalgia in women with fibrocystic breasts. According to TCM theory, dong quai dissolves blockages and relieves blood stagnation, and is thus a common ingredient in formulae for mastalgia.

Flax Seed and Evening Primrose Oil

Flax seeds are the richest source of plant-based omega-3 fatty acids, with a-linolenic acid (ALA) being the primary fatty acid (18:3n-3).⁵¹ These fatty acids are considered strongly anti-inflammatory, being precursors for the anti-inflammatory series prostaglandins (PGE3). Flax seeds are also rich in fibers called lignins. Like isoflavones in soy and other foods, lignins and their associated phenolic compounds are classified as phytoestrogens.^52,53 Flax seeds are an especially rich source of dietary lignins, with 75 to 800 times more than any other food source.^51,54 Research has shown lignins to be a promising agent for binding excess sex hormones, including testosterone and estrogens. Through both its anti-inflammatory and possible anti-estrogenic effects researchers believed that flax may prove a beneficial treatment for fibrocystic breasts. One study examined the effect of eating one muffin daily supplemented with 25 g of ground flax seeds in 127 women with mastalgia.⁵⁵ Women experienced a significant reduction of symptoms; however, the full results of this study were never published and thus it is unknown how long women needed to take the flax seed–enriched muffins, what symptoms were reduced, what the degree of symptom reduction was, or if there was any placebo control to assess for the considerable level of spontaneous remission (60% to 80%) of symptoms in women with breast pain over time.⁵⁵ Evening primrose oil (EPO), is a rich source of omega-6 essential fatty acids (EFAs). EFAs are precursors to either series 1 or 2 prostaglandins, depending on substrate availability. The more omega-6 EFAs there are in the diet, the more likely it is for the inflammatory series prostaglandins to be made; conversely, the less omega 6 EFAs there are in the diet, the more likely it is for anti-inflammatory series 1 prostaglandins to be produced. Because of EPO’s potential anti-inflammatory properties, two randomized placebo-controlled, double-blind clinical trials and one open-labeled trial of EPO in both cyclic and noncyclic mastalgia have been conducted. One double-blind, placebo-controlled randomized study in 73 women with either cyclic or noncyclic mastalgia found that 1000 mg of EPO or placebo three times daily over 3 months significantly reduced symptoms of pain and tenderness in the women who received EPO compared with placebo.⁵⁶ In a similar study, 291 women with severe persistent breast pain given either placebo or 1000 mg EPO three times daily for 3 to 6 months found that 45% of women with cyclic pain improved. Further, 27% of women with noncyclic breast pain improved compared with 9% in the placebo group.⁵⁷ In a nonrandomized open-labeled study, 94 women with cyclic and 32 women with noncyclic mastalgia received 3 g of EPO for at least 4 months. Severity of pain was diminished in a “clinically useful”⁴⁰ manner in 58%⁴⁹ of the women with cyclic mastalgia and 38%¹² of the women with noncyclic mastalgia taking EP. Unfortunately, all three of these studies are difficult to assess because of lack of reporting of how pain and symptoms were measured and how great the effect, and thus how clinically relevant the effect of EPO is in women with breast pain.⁴⁰ The recommended dose of flax oil to treat and prevent mastalgia and nodularity is two to four 500-mg capsules twice daily or 1 to 2 tablespoons of the oil daily. One to three grams daily is the recommended dose of ground seeds.⁵⁸ A typical dose of EPO is 1500 mg daily.

Red Clover

Red clover is rich in isoflavones, especially genistein and daidzein. Genistein and daidzein have weak estrogenic effects, which have led researchers to hypothesize that genistein may compete with stronger endogenous estrogens such as estradiol for estrogen receptors; although what effects this may have on breast tissue is unclear at this time. One unpublished study found that a red clover extract had a significant effect on improving mastalgia. No further information is available concerning this trial.⁵⁹

Topical Applications

Elimination of Coffee, Tea, and Other Caffeinated Products

An association between caffeine, or methylxanthines, and fibrocystic breast disease has been reported but remains controversial. In one study of a group of 102 women who had mammograms performed to measure the level of fibrocystic breast disease, a strong correlation was found with both caffeine and total methylxanthine ingestion and fibrocystic breasts as determined by a series of questionnaires.⁶⁰ Similar results were found in a large case control study of 634 women.⁶¹ Other studies, however, have found only weak associations. Normal fluctuations in hormonal effects on breast tissue and difficulty in consistently measuring caffeine or methylxanthine intake make it difficult to conclusively demonstrate a causal relationship.^62,63 In a review of the literature presented on AltMedex, the following studies are cited: A controlled clinical trial showed no clinically or statistically significant effects of alcohol- or methylxanthine-free diets on signs and symptoms of fibrocystic breast disease. One hundred sixty-two women with clinical and thermographic diagnoses of fibrocystic breast disease completed the study with evaluation at 6 months. It was concluded that abstinence from alcohol or methylxanthine-containing beverages is not likely to substantially reduce severity of fibrocystic breast disease within a few months.⁶⁴ A case control study examined the relationship between coffee consumption and the development of benign breast disease involving the analysis of 854 cases of histologically diagnosed benign breast disease and 1748 control subjects. No association between coffee consumption and benign breast disease was found; neither was a dose–response relationship between methylxanthine consumption and benign breast disease development noted. These results suggest no association between caffeine intake and the development of benign breast disease.⁶⁵ In a randomized study, 158 women with breast concerns were divided into two groups; one group abstained from consumption of methylxanthine-containing foods and beverages. The second group (controls) had no dietary restrictions. The patients were re-examined at 4 months for palpable breast findings. One hundred forty patients completed the study. There was a statistically significant decrease in clinically palpable breast findings in the abstaining group compared with controls, but the absolute change was minor and may be of little clinical significance. This study offered little support for the claim that caffeine-free diets are associated with clinically significant improvement in benign breast disease.⁶⁶ In a study of 66 patients, restriction of dietary caffeine ingestion can cause improvement in fibrocystic breast disease. Graphic stress telethermometry (GST) was performed as an objective monitor for fibrocystic breast. At baseline, an average score of 83.5 on GST was observed in these women. Following dietary methylxanthine restriction, these scores were observed to be an average of 69.5 at 2 months and 55.5 at 6 months. Forty-two of the 66 patients had decreases in GST scores of more than 20 points at 6 months. Eighty-five percent of the patients showed improvement in GST patterns at 6 months, 15% of patients showed no change, and none showed worsening in GST patterns. Subjectively, at 6 months, 22 of 66 patients reported marked improvement, 30 of 66 moderate improvement, 6 of 66 mild improvement, and 8 of 66 no change in symptoms of fibrocystic breast disease. At pretreatment, 78% of patients had 2+ or 3+ nodularity on palpation. At the 6-month examination, 89% of patients had no or 1+ nodularity on palpation (91% had improvement, 9% had no change, and none had worsening). In 85 US women with clinical and mammographically confirmed fibrocystic disease, complete abstention from methylxanthine consumption resulted in complete resolution of fibrocystic breast disease in 82.5% and significant improvement in 15% of the patients studied.⁶⁷

Vitamin E and B₆ Supplementation

Supplementation with vitamin E (400 to 800 IU) may be beneficial for reducing mastalgia and nodularity of fibrocystic breasts and pyridoxine (vitamin B₆/50 to 100 mg) to reduce breast tenderness and pain.^68,69 Women are also encouraged to increase dietary fiber and complex carbohydrates, reduce dietary fat to 15% to 20% of their diet, and move toward a more plant-based diet, rich in phytoestrogens. A recent review examined various dietary therapies, and their potential effects in treating fibrocystic breasts.³⁸ The review found that some dietary therapies, including vitamin E and B₆, do not have adequate evidence to support their use in fibrocystic breasts. Studies were either of poor quality or had too few study participants to make definitive conclusions. Because of the dynamic nature and very high placebo response (20%) in fibrocystic breast complaints, only well-designed studies with large numbers of participants can address the efficacy of these treatments. Indeed, better-designed studies of vitamin E have all showed no significant effect on any parameter of fibrocystic breast. Studies on reducing caffeinated products from the diet have been variable, some showing positive outcome, others showing no benefit at all. This review found no studies that had examined the effect on fibrocystic breasts of low-fat diets, increased dietary fibers, soy isoflavones, or a more plant-based diet. However, there are considerable mechanistic data, including increasing unabsorbable estrogen conjugates for excretion, reducing the recirculation of estrogen, and positively affecting bowel microflora populations that support the use of these dietary strategies. The general health benefits of adjunct therapies such as adding vitamin E, reducing poor-quality fat intake, or reducing caffeine consumption suggest that these may be worthwhile strategies to try.³⁸

Exercise

It is important to evaluate whether women with breast pain are exercising appropriately and properly. Some women who believe that they are experiencing breast pain or tenderness are instead having chest wall pain, often resulting from inappropriate or overexercise, especially strength-building exercises that emphasize the pectoral muscles.³⁹ No studies have examined the impact of any type of exercise on the symptoms or nodularity of fibrocystic breasts. Consequently, it is difficult to know what duration, type, or frequency of exercise would most benefit women with fibrocystic breasts.

Clothing

Inadequate support of the breasts is thought to lead to suspensory ligament strain, which may cause or contribute to pain and tenderness.⁵⁵ No randomized controlled studies have examined breast support and its relationship to breast pain.

Stress Reduction

No studies have examined the effect of stress, anxiety, depression, or sleep disturbances on fibrocystic symptoms. However, many other pain syndromes, including fibromyalgia and vulvar pain, are closely associated with levels of “distress” in a woman’s life.⁷⁰ No randomized clinical trials have been conducted using acupuncture for fibrocystic breast symptoms; however, several open label trials have found that up to 95% of women’s mastalgia was improved after acupuncture treatment.

SYMPTOMS

The following symptoms (Box 7-3), alone or in constellations, should alert a woman and her practitioner to the possibility of endometriosis: premenstrual pain, dysmenorrhea, dyspareunia, generalized pelvic pain throughout the month without other explanation, atypical periods, nausea, vomiting, exhaustion, bladder problems, frequent infections, dizziness, painful defecation, rectal pain, low backache, irritable bowels, or infertility. The far-reaching nature of these symptoms and their possible association with other conditions helps to explain why this condition is difficult to diagnose. Dysmenorrhea and painful intercourse become even more suggestive of endometriosis if they begin after a history of relatively pain-free menstruation and intercourse. Severity of pain is not indicative of the severity of the condition, with the exception of severe pain, which is associated with extensive endometriosis and adenomyosis (deeply infiltrating endometriosis.)^3,78 Other causes of pelvic and abdominal pain or bleeding must be ruled out.

DIAGNOSIS

Endometriosis is most commonly seen in women 30 to 40 years old and is rarely found in postmenopausal women. Endometriosis has been thought not to occur prior to menarche; however, the rates of this condition are increasing among teenagers.³ The site of lesions, although widely variable, is generally the posterior cul de sac or ovaries. Diagnosis is based on pelvic examination, diagnostic ultrasound, or laparoscopy, with definitive diagnosis based on laparoscopy. CA-125 is a serum antigen found in endothelial cervical cancer that can also be found to be elevated in women with endometriosis. The diagnostic importance of the test for endometriosis is still uncertain; however, there appears to be some predictive value demonstrating which women might benefit from specific treatments on the basis of CA-125 levels, and CA-125 levels may indicate whether improvement is occurring.⁸⁸ Endometriosis is staged based on the location(s) of the endometrial tissue as follows:

CONVENTIONAL TREATMENT APPROACHES

Medical treatment of endometriosis includes both pharmaceutical and surgical approaches. Pharmaceutical treatments provide only suppression of the disease; they do not exact a cure.³ Decisions regarding treatment are based on endometriosis severity and staging, symptom picture, and ultimately, the woman’s needs and goals, for example, desire for children in the future.⁸⁹ For women experiencing mild symptoms (or none) and for women who are close to menopause, the appropriate treatment may be to do nothing.⁷⁸ For women with mild to moderate symptoms, and those who desire pregnancy, the appropriate pharmacologic therapy should be considered, and if necessary, can be combined with conservative surgery. It should be noted that, in spite of medical treatment, endometriosis has a high recurrence rate of 5% to 20% unless total hysterectomy and bilateral oophorectomy are performed. With pharmacologic interventions, pain typically resumes upon cessation of medications, although initially with pain that is less intense than prior to treatment. Pain relief, pregnancy rates, and recurrence rates are similar with all treatment methods. The goal of pharmaceutical treatment is to interrupt patterns of endometrial stimulation and bleeding.⁸⁹ Pharmaceutical options include nonsteroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies (progestins, GnRH analogs, Danazol, and oral contraceptives). NSAIDs (i.e., ibuprofen, naproxen) may be prescribed for mild to moderate pain. They are relatively safe for short-term symptomatic relief; however, long-term use can lead to health consequences, including gastrointestinal bleeding, and should be avoided in patients with a history of peptic ulcer disease or renal failure. It should be noted that none of these therapies demonstrates significant benefit over the others, and all are associated with a high recurrence rate (20%–50%) upon discontinuation of the therapy.⁸⁹ Progestins (medroxyprogesterone acetate, i.e., Depo-Provera) suppress the response of endometrial tissue to cyclic hormones, leading to atrophy of this tissue and decreased pain. They are typically better tolerated than oral contraceptives (OCs), with fewer side effects, and are less costly than Danazol and GnRH analogs. This is often considered the pharmaceutical treatment of choice for endometriosis, although the FDA no longer supports the use of Depo-Provera for this purpose. Side effects include weight gain, fluid retention, and breakthrough bleeding. Depression is a common significant side effect of medroxyprogesterone use. In high doses, medroxyprogesterone can adversely affect lipid profiles, and may lead to a state of hypoestrogenism, with subsequent potential for bone loss. Oral contraceptives are used to control pain in women not desiring pregnancy. The combined effect of estrogen and progesterone is to induce a state of “pseudopregnancy,” and appears to lead to a 90% rate of improved symptoms with long-term use. Side effects include all those typically associated with general OC use. Danazol, a synthetic testosterone, is used for the treatment of mild to moderate endometriosis in women who desire fertility but not necessarily in the immediate future. It induces a state of “pseudomenopause,” eliminating mid-cycle FSH and LH surges. Once considered the optimal treatment for endometriosis, it is now considered no more effective than any of the other pharmaceutical treatments. Possible side effects include weight gain, fluid retention, fatigue, decrease in breast size, hirsutism, atrophic vaginitis, hot flashes, muscle cramps, emotional fluctuations, voice changes, spotting, and decreased HDL cholesterol levels. In some patients it may cause hepatocellular damage; thus is contraindicated in patients with liver disease, and liver enzymes should be monitored in all patients during treatment. It is also contraindicated in patients with a history of hypertension, hyperlipidemia, congestive heart failure, renal impairment, and pregnancy.^3,25,89,90 Gonadotropin-releasing hormone analogues (GnRH-a, e.g., Leuprolide) also cause a suppression of endometriosis via a “pseudomenopausal” state. GnRH treatment does not carry the same risks of negative impact on serum lipids and lipoproteins compared with Danazol; however, it does interfere with calcium metabolism via stimulation of a hypoestrogenic state, and thus can cause osteoporosis. Even after only 6 months of use, a 6% to 8% loss in trabecular bone has been observed. It can take up to 2 years after cessation of treatment to replace this bone loss; thus a treatment is usually restricted to 6-month durations.^3,91

Surgical options include conservative surgery (destruction and removal of endometriomas while maintaining reproductive function) and radical surgery (hysterectomy, generally accompanied by bilateral salpingo-oophorectomy). Conservative treatment involves the removal of endometriotic lesions and restoration of normal anatomical relationships via removal of adhesions to the greatest extent possible, with the goal of pain relief, and possible restoration of fertility when achieving pregnancy is desired and has been impaired by the condition. In approximately one-fourth of women treated surgically, however, there is no improvement in fertility even if the disease was considered mild. Procedures include knife excision, laser surgery, electrocautery, curettage, and laparotomy. The worse the disease, the worse the statistics for conceiving after surgery.^92,93 Recurrence of endometriosis after surgery is dependent on the skill of the surgeon and extent of disease, and as with other endometriosis treatments, rates may be as high as 20%. Hysterectomy will not remove lesions outside the uterus and is not considered a successful treatment when used primarily to reduce the symptom of chronic pelvic pain. Surgery carries the risk of complications, especially adhesion formation and continuing pain. The total rate at which symptoms of chronic pelvic pain returned after drug treatment is estimated to be 5% to 15% at the end of 1 year, or up to 50% at the end of 5 years. Nonetheless, the risks of surgery or medication may be justifiable for severe pain that does not respond to other methods, especially if menopause is not expected for some time. There is a concern that diagnostic microsurgery may aggravate or cause the transfer of viable endometrial cells into general or lymphatic circulation, thereby causing the very condition being identified. Because of this, some wary clients choose natural treatment approaches for the condition without a certain diagnosis, believing that if the signs and symptoms respond, the holistic prescription was correct for the presumed diagnosis.

BOTANICAL TREATMENT

Herbalists share the conventional medical perspective that endometriosis has multifactorial causes. The botanical approach, however, takes into consideration immune dysregulation, inflammation, hormonal dysregulation, diet and nutritional status, lifestyle, exposure to exogenous estrogens, and the woman’s emotional and psychological mechanisms for coping with this condition as components of a whole picture. Given that nonradical medical treatments for endometriosis are purely suppressive rather than curative, the high recurrence rate of endometriosis upon cessation of pharmaceutical treatment, and the potential for drug-related or surgical side effects, botanical medicines may provide women with a safe alternative for symptomatic pain relief, reduction of inflammation, prevention and reduction of recurrent vaginal and pelvic infections, stress reduction, and improvement of overall immunologic health (Table 7-4). By applying a comprehensive natural health care protocol, many cases of endometriosis can also be resolved. The herbal approach should also include as part of the protocol, herbs that address concomitant discomforts arising from the condition, such as irritable bowel complaints or depression.

Many herbs have multiple actions. Varying degrees of success have been obtained when improving as many of the known cofactors as possible. However, the mechanisms behind the success of herbal protocol are not well elucidated nor understood, and clinical successes are inconsistent. In fact, many Western herbalists consider endometriosis hard to completely “cure,” and ultimately focus on symptom control and overall health improvement. There are well-developed treatment protocols for the treatment of endometriosis in traditional Chinese medicine (TCM) that have been associated with successful treatment. By applying a comprehensive natural protocol, endometriosis may be entirely resolved in some cases, and made significantly less problematic in many. The following section discusses the general Western botanical treatment approaches for endometriosis as well as a brief overview of TCM approaches. Fertility treatments appear in a chapter devoted to that subject. Also see chronic pelvic/vaginal pain, vaginal infection, dysmenorrhea, and other relevant topics under separate headings.

The following factors have been noted in endometriosis patients, but this does not explain why all patients with SOME of these findings do not necessarily have the other syndromes associated with these factors (e.g., PMS):

Attention to these factors may help some women with symptom reduction and regression of size and infiltration of endometriotic tissue.

DISCUSSION OF BOTANICALS

For many women with endometriosis pain is the single most debilitating aspect of this condition (other than chronic fertility problems in women desiring pregnancy). Therefore, pain management should be an important focus in the care of women with this condition. Herbalists reliably employ a number of herbs for the treatment of pelvic and abdominal pain, many of which have a long history of traditional use for painful gynecologic conditions. These herbs can be used singly but are generally used in various combinations with other herbs in these categories, or as part of a larger protocol. Analgesic herbs are used for generalized or local pain of an aching or sharp quality and include black cohosh, black haw and cramp bark, chamomile, corydalis, pulsatilla, dong quai, ginger, and Jamaican dogwood. Corydalis, Jamaican dogwood, and pulsatilla are especially dependable for moderate to serious pain. Pulsatilla is considered specific for ovarian pain.²² Antispasmodics are typically used for cramping pain, but also may be used for sharp or dull pain, aching, and drawing pains in the lower back and thighs, and include, such as wild yam, the viburnums (cramp bark and black haw), black cohosh, chamomile, and ginger. Dong quai’s traditional TCM uses for gynecologic conditions, specifically for conditions of blood vacuity and stasis, the latter of which endometriosis may be considered among, along with its antispasmodic, anti-inflammatory, and immunomodulatory qualities, make it an important herb to consider.^25,50,94 Many antispasmodics and anti-inflammatories, such as wild yam, the viburnums, ginger, and chamomile are specific not only for uterine pain, but also for intestinal, bowel, and urinary pain and irritability, making them uniquely suitable for endometrial pain and accompanying bowel and bladder discomforts. This is important to keep in mind, because the pain of endometriosis is related to irritation of tissue by endometrium outside of its normal site in the uterus. Sedatives are useful when there is the need to induce deep rest or sleep to obtain pain relief, and include

California poppy, a combination of black cohosh and cramp bark, or a combination of cramp bark and Jamaican dogwood. Valerian and hops are also useful sedatives. The successful use of these herbs for pain depends largely upon adequate dosing and frequency of administration.

Hormonal Modulation

Predicated on the belief that steroid hormones are the primary regulators of the growth and activity of ectopic endometrial tissue, therapies aimed at hormonal modulation have been the foundation of conventional therapy for endometriosis, and have also featured prominently in botanical protocol.⁸¹ Unfortunately, even less is known about the effects of botanical therapies on the endocrine system than about pharmaceutical medications. The goal of pharmaceutical therapies is to create an acyclic, low-estrogen environment that prevents bleeding, leads to atrophy of ectopic implants, and possibly minimizes retrograde bleeding. However, endometrial tissue may be histologically different than normal uterine endometrial tissue, and may respond differently to hormonal stimulation. Again, much remains unknown about this enigmatic condition.⁸¹ Several botanicals are frequently used as hormonal modulators, in conjunction with other herbs discussed in this chapter. Little research is available on their application in endometriosis. But as part of a comprehensive protocol, many herbalists and naturopathic physicians report positive outcomes for achieving the goals established earlier in this paragraph. There is also some small discrepancy in the herbal literature as to which herbs should be avoided due to potential exacerbating hormonal effects. For example, Mills and Bone caution against the use of what they refer to as “estrogen promoting herbs” such as false unicorn (Chamaelirium luteum), the use of which should primarily be avoided in clinical practice due to its endangered status) and wild yam (Dioscorea villosa); however, wild yam is used widely for abdominal and pelvic cramping pain associated with the condition, whereas the late Silena Heron included these in endometriosis protocol and authors Hobbs and Keville, in Women’s Herbs, Women’s Health, mention wild yam as an antispasmodic specifically for endometriosis.²² There would actually potentially be numerous plants in this category, ranging from fennel and hops to common foods such as legumes, most of which are rich in phytoestrogens, which would need to be avoided on this presupposition. One study on the estrogenic contents and activity of commonly used herbs found that soy, red clover, licorice, hops, and fo-ti have a large amount of measurable estrogen bioactivity not previously reported. Chaste tree berry, black cohosh, and dong quai did not have measurable activity with the methods used in the study.¹¹⁴ Confusion stems largely from the fact that so much remains unknown about the endocrine effects of botanicals, and until more information is available, rational conclusion are hard to draw, suggesting that caution and observation of clinical response are required. Women with a predisposition to estrogen-dependent cancers are probably wise to avoid unnecessary and excess consumption of herbs with estrogenic effects. However, it should also be considered that herbs that competitively bind with estrogen receptors might actually displace endogenous estrogen with weaker, plant-based estrogens, actually decreasing a woman’s overall estrogen response.

Blue Vervain

Blue vervain (Fig. 7-3) has a long history of use in traditional European herbalism as an emmenagogue and galactagogue, and a contemporary popularity among herbalists experienced in women’s reproductive care for its regulating effects on gynecologic complaints, particularly for irritability associated with PMS. A BIOSIS database search and extensive review of the herbal literature references yields very little data on the medicinal uses of this plant, although historical references to its use as a treatment for rheumatism were identified.^29,115 A single study from 1974 on the effect of this herb on the uterus and its interactions with prostaglandins was identified but not obtainable. According to studies cited in Wichtl et al., hot water extracts of European verbena stimulates luteinizing hormone (LH) and FSH secretion. Other noted endocrine effects include antithyrotropic and abortifacient effects via inhibition of human chronic gonadotropin (hCG). Verbena has also demonstrated immunomodulatory effects, primarily through inhibition of phagocytosis by human granulocytes.²⁹ The German Commission E cites its uses, among other things, for irregular menstruation, nervous disorders and exhaustions, and complaints of the lower urinary tract; however, the efficacy for these claims remains unsubstantiated.²⁹ Many herbalists consider it an excellent herb for “sluggishness of the liver,” and attribute its hormonal action to stimulated liver function and subsequent actions on hormonal metabolism and elimination. It is typically used as a small part of a larger general formula aimed at treating underlying causes of endometriosis.

Figure 7-3 Blue vervain (Verbena officinalis).

Photo by Martin Wall.

Chaste Berry

Chaste berry has a reputation for its ability to regulate female menstrual cycles and relieve complaints and complications stemming from dysregulation of sex hormones. Clinical trials support the use of Vitex for menstrual irregularities (secondary amenorrhea, oligomenorrhea, polymenorrhea), relief of PMS symptoms, mastalgia, latent hyperprolactinemia, and infertility due to luteal phase dysfunction.¹¹⁶ The effects of Vitex on estrogen levels remains uncertain, with one study (the full details of which were undisclosed) demonstrating its ability to elicit estrogen-like effects (increased uterine growth) in ovariectomized rats, and another reporting decreased estradiol levels, whereas other studies have reported no effects or were inconclusive.¹¹⁶ Its efficacy in the treatment of endometriosis, for which is it widely used by herbalists, is supported by clinical observation, with no research identified for its use for this condition.

Cotton Root

Cotton is predominantly used as a uterine tonic and to stimulate uterine contractions. Gossypol, the active ingredient in the roots and seeds of cotton, has been used in the treatment of gynecologic disorders ranging from uterine myomas to menopausal bleeding, based on the discovery that regular cooking with cottonseed oil over long periods of time leads to amenorrhea and endometrial atrophy in females. Several studies over a 15-year period have demonstrated short-term efficacy of up to almost 90% in the treatment of endometriosis, and long-term effectiveness after 1 to 3 years of 54% to 63%. Treatment is typically accompanied by amenorrhea persisting for up to 6 months in 80% of women, and up to 1 year in 16% of women, with 4% experiencing amenorrhea lasting longer than 1 year.¹¹⁷ Gossypol is reported to antagonize the actions of estrogen and progesterone, and may mimic a pseudomenopausal state.¹¹⁷ A frequent side effect of gossypol treatment is hypokalemia, which is treated with administration of slow-releasing potassium salts. High-dose programs can lead to elevated liver enzymes, nausea, edema, and palpitations, as well as possible rash, reduced appetite, fatigue, and possible inhibition of thyroid function and mitochondrial energy metabolism. This compound is not available in the West, and would be considered a pharmaceutical drug rather than a botanical product were it made so. Studies on the use of cotton root bark, used, as a partus-preparator, emmenagogue, and abortifacient by Western herbalists, as an herbal extract for endometriosis have not been conducted.

St. John’s Wort

According to modern clinical research, St. John’s wort is commonly used for the treatment of mild to moderate depression and additionally has been shown to exhibit antiviral activity. In traditional herbal medicine currently and historically, it is used internally for anxiety and as a general nervous system tonic, whereas externally it is used as a primary application for scrapes and burns. Recent concerns regarding the interaction between St. John’s wort and numerous pharmaceutical drugs have led to a host of contraindications for use of this herb. One such contraindication is the use of oral contraceptives, as it has been shown to induce the activity of cytochrome P450 3A4 (CYP3A4) and increase the clearance of numerous drugs and steroids, such as cortisol and ethinyl estradiol.¹¹⁸ This interaction suggests the potential for use of St. John’s wort to positively interfere with estrogen binding in states of estrogen excess, for example, in endometriosis. A limited number of studies have evaluated the estrogen-binding capacity of St. John’s wort extracts. One study by Simmen et al. found that estrogen binding was 50% inhibited by the bioflavonoid I3,II8-biapigenin at micromolar concentration in the CNS.¹¹⁹ Use of St. John’s wort to deliberately modulate estrogen levels represents a potentially novel application for this botanical. This herb should also be considered in endometrioses treatment for its beneficial role in the treatment of mild to moderate depression, which may accompany this condition in women who suffer with it chronically.

NUTRITIONAL CONSIDERATIONS

In addition to a balanced whole foods diet, use high-quality oils, and minimize consumption of caffeine, sugar, alcohol, red meat, and large amounts of dairy. Also avoid excess refined carbohydrates, and address hypoglycemia with frequent small meals and snacks with high protein and complex carbohydrates. Adequate consumption of essential fatty acids is important; encourage two to three servings of salmon or other high-quality cold-water fish per week. Fatty acid–mediated mechanisms have demonstrated decreased cytokine-induced adhesion molecule expression, thereby reducing inflammatory leukocyte–endothelium interactions and modified lipid mediator synthesis, thus influencing the transendothelial migration of leukocytes and leukocyte trafficking in general. Even the metabolic repertoire of specific immunocompetent cells such as cytokine release or proliferation is modified by n-3 fatty acids. Beyond this these fatty acids regulate lipid homeostasis shifting the metabolic pathways toward energy supply, thus optimizing the function of immune cells. Because of the regulatory impact on different processes of inflammatory and immune cell activation n-3 fatty acids provide positive effects on various states of immune deficiencies and diseases with a hyperinflammatory character, among which selected examples are presented.¹²⁰

Choose Between*:

B vitamin supplementation may assist in hepatic metabolism of estrogens and are recommended as part of an overall multivitamin and mineral supplement.

ADDITIONAL THERAPIES

DIAGNOSIS

Cervical dysplasia is usually asymptomatic and most commonly discovered upon routine Pap smear. In contrast, cervical cancer may be asymptomatic or present with abnormal vaginal bleeding. Pap testing has significantly reduced mortality from cervical cancer, a privilege of developed nations that if made available worldwide would nearly obliterate this disease. Current guidelines recommend that all women over aged 18 have a Pap test done every 1 to 3 years, depending on individual risk factors and medical history. With routine Pap smears, advanced morbidity and mortality from cervical cancer should be entirely preventable, particularly because it is a slowly progressing cancer allowing plenty of time for detection and treatment. Sadly, 50% of all women diagnosed with cervical cancer have not had a Pap smear in greater than 10 years. Any suspicious lesion should be biopsied directly. Colposcopy-directed biopsy usually provides enough clinical evidence for an accurate diagnosis. The diagnosis of cervical dysplasia is largely anxiety provoking for women because of the association between dysplasia and carcinoma. Therefore, it is important that practitioners take the time to thoroughly explain to each woman the level of concern that is warranted by her degree of dysplasia, and compassionately review options with her.

CONVENTIONAL TREATMENT APPROACHES

Medical treatment depends on the severity of the lesions. For women with preinvasive cervical disease, treatments options include laser therapy, cryotherapy, loop electrical excision procedure (LEEP), and conization biopsy. Most physicians have abandoned laser and cryosurgery because of the inaccuracy of treatment compared to LEEP. The depth of the treatment and amount of collateral tissue damage is easier to control with a LEEP. The LEEP removes tissue precisely and cauterizes simultaneously. Cone biopsy is the removal of a cone-shaped amount of cervix the depth of the entire cervix. In both, the LEEP and the cone biopsy the physician is trying to obtain clean borders, meaning that there is no evidence remaining of cervical dysplastic cells. If the woman has progressed to cervical cancer treatment, it usually consists of a total hysterectomy and/or radiation treatment. Conventional treatment is an efficient solution, usually covered by insurance. However, conventional treatments often cause permanent scarring and do not address potential underlying causes. Scarring can interfere with women’s ability to conceive by obstructing the endocervical canal with scar tissue, and damaging cervical crypts that are important in providing proper nutrition for advancing sperm and the proper formation of cervical mucus. The scarring also may interfere with cervical dilatation in labor. Further, conization can occasionally lead to “incompetent cervix” during pregnancy, necessitating

cervical cerclage, in which a suture is inserted into the cervix to allow the woman to maintain pregnancy and prevent premature labor.

Because of the risks associated with sexually transmitted infections and subsequent cervical dysplasia, current sexual partners should be screened and treated for HPV as necessary. Adolescent girls should be educated about the risk factors for developing cervical dysplasia. The sociologic components of women’s health also cannot be ignored. A history of sexual abuse, for example, is not an uncommon clinical finding in women with a history of cervical dysplasia.

BOTANICAL AND NATUROPATHIC TREATMENT

Intrinsic to both herbal and naturopathic treatment of cervical dysplasia is the belief that conventional therapy alone does not address a woman’s underlying propensity to dysplasia, nor does it address preventable causes. This is significant as the 5-year return rate, with conventional therapies is as high as 75%. In contrast to conventional approaches, botanical and naturopathic treatments attempt to addresses multifactorial causes, treating the woman, not just her cervix. A disadvantage is that natural medicine protocols are demanding, inconvenient, and potentially costly, requiring multiple office visits. Naturopathic and botanical medicine practitioners emphasize a number of therapies including the use of immune enhancing, anti-inflammatory, hormone-regulating, and antiviral botanicals both for internal and topical treatments.^25,121 Adaptogens often feature prominently in a botanical program to address immune and endocrine function. Stress can depress immune response, which can increase viral activation. Recent lifestyle changes or stressors, even as seemingly benign as exposure to increased amounts of sunlight, may suppress the immune system sufficiently to cause viral activation.¹²² Environmental causes of gynecologic disease—ranging from exposure to excess exogenous estrogens to stress—must be addressed in the long-run for the benefit of all women. (See Endometriosis for a brief discussion of the role of exogenous estrogens on gynecologic health.)

Herbal and naturopathic treatment for the treatment of cervical dysplasia should occur in the context of a complementary relationship with a conventional care provider and in conjunction with appropriate medical care. The development of cervical cancer from dysplasia is highly preventable with proper integrated conventional and natural medical treatment.

DISCUSSION OF BOTANICALS

Marshmallow

Marshmallow root (Fig. 7-4) is a polysaccharide-rich herb, loved by herbalists for its soothing, demulcent properties.²⁵ The mucilaginous quality of aqueous extracts and moistened powdered herb provides a protective, soothing coating to mucosa; thus, it is commonly included in preparations for throat, GI, and vaginal mucosal irritation.⁹⁷ Several studies have found the herb efficacious, in combination with other specific herbs, for the treatment of cough, and the herb is approved for use by the German Commission E for the treatment of irritation of the oral and pharyngeal mucosa and mild inflammation of the gastric mucosa.⁹⁵ The root also exerts immune-enhancing and antibacterial effects.²⁵

Figure 7-4 Marshmallow (Althea officinale).

Photo by Martin Wall.

Reishi

Reishi (Fig. 7-5) is a medicinal fungus with a long history of use as a Chinese folk medicine for promotion of health and longevity. Numerous in vitro and animal studies have demonstrated antitumor and immunomodulatory effects of Reishi mushrooms.¹⁸⁷ An OVID search for this herb yielded over 900 papers reporting on in vivo and in vitro effects. A wide range of antitumor and immunomodulatory mechanisms have been purported and observed, with the water extract and the polysaccharide fraction, as well as the alcohol extract or the triterpene fraction, and include enhanced function of antigen-presenting cells, the mononuclear phagocyte system, humoral immunity, and cellular immunity.^188,189 Reishi polysaccharide peptide (Gl-PP) has demonstrated antitumor effects in mice and potential antiangiogenesis, a reduction of Bcl-2 antiapoptotic protein expression and an increase of Bax proapoptotic protein expression; therefore, inducing cell apoptosis might be one of the mechanisms of action in inhibition of human carcinoma cells. High doses of Gl-PP resulted in a decrease in the secreted vascular endothelial growth factor (VEGF). Taken together, these findings support the hypothesis that the key attribute of the antiangiogenic potential of Gl-PP is that it may directly inhibit vascular endothelial cell proliferation or indirectly decrease growth factor expression of tumor cells.¹⁹⁰ It has been demonstrated that G. lucidum induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancer cells PC-3.¹⁹¹ Experimental results on cell-mediated immunity showed that G. lucidum could increase the percentage of CD5+, CD4+, and CD8+ T lymphocytes. Experimental results on humoral immunity in horses showed that G. lucidum could help horses to produce a significantly higher quantity of specific antibodies in a shorter time.¹⁹² Although the pharmacology and clinical application of water extracts of G. lucidum have been extensively documented, little is known regarding its alcohol extract. In the present study, the antitumor effect of an alcohol extract was investigated using MCF-7 breast cancer cells. The extract inhibited cell proliferation in a dose- and time-dependent manner, which might be mediated through upregulation of p21/Waf1 and downregulation of cyclin D1. Furthermore, this compound can directly induce apoptosis in MCF-7 cells, which might be mediated through upregulation of a proapoptotic Bax protein and not by the immune system. There are likely multiple mechanisms underlying the antitumor effects of G. lucidum.¹⁹³ G. lucidum also demonstrated antioxidant activity, free-radical scavenging, and chelating abilities.¹⁹⁴ No specific studies were identified on the use of G. lucidum for the treatment of HPV infection or cervical dysplasia; however, given the mechanisms of action of this herb, this may be a promising area of research, and certainly merits consideration of this herb in an immune-enhancing protocol.

Figure 7-5 Reishi (Ganoderma lucidum).

Photo by Martin Wall.

DIAGNOSIS

Diagnosis of CPP is based on identifying the underlying cause(s). It also may be a diagnosis of exclusion, with no identifiable etiology. Careful attention should be paid to the history and physical examination, particularly a thorough pelvic examination to evaluate for tenderness, pelvic mass, adhesions, or prolapse. Testing may include ultrasound, laparoscopic examination, pregnancy test, CBC, vaginal and cervical cultures, Pap smear, evaluation for GI disorders, and urologic examination.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis in CPP is really a matter of identifying the possible causes of pain (Table 7-6) and treating the etiology while addressing the pain and concomitant symptoms. In patients under 30, the most common causes of pelvic pain include endometriosis and pelvic inflammatory disease; in older women, causes most likely include uterine myoma, adenomyosis, or pelvic relaxation. It is critical to rule out any serious or life-threatening causes, as well as to assess for depression, anxiety, and serious mental health disorders.

TABLE 7-6 Common Causes of Chronic Pelvic Pain

Analgesia

The history of botanical medicine reveals many herbs that have been used for the treatment of a variety of types of pain.²⁰⁸ Many traditional medicines have actions such as inhibition of platelet-activating factor, cyclooxygenase, prostaglandin formation, or arachidonic acid pathways.²⁰⁹ Although not typically as fast-acting as conventional medications, repeated appropriate dosing over a short period of time, such as 1 to 2 hours, and continued as needed, often leads to satisfactory temporary alleviation of pain. Several herbs are reputed for their efficacy in the treatment of pain of gynecologic origin, as well as more generally (see Dysmenorrhea).

Black Cohosh

Black cohosh has historically been used by Northeast Native American tribes as an analgesic and as an emmenagogue.²¹⁰ The Eclectics used a resin of black cohosh specifically as a uterine tonic and in the treatment of dysmenorrhea and a number of other painful spasmodic or cramping gynecologic complaints.²¹¹ It was also used in the treatment of deep muscle drawing in the legs, loins, and back, dull aching of the bowels, ovarian pains of a dull, aching quality, dragging uterine pain, and delayed menses with dull pain and muscle soreness. Felter specifically describes a condition called “rheumatism of the uterus” for which this herb was prescribed.⁹⁹ The plant’s anti-inflammatory and analgesic properties are attributed to its aromatic acids, which appear to inhibit prostaglandin production. The herb is approved for use in Germany for the treatment of premenstrual discomfort and menstrual cycle pain.²⁵

California Poppy

California poppy (Fig. 7-6) traditionally has been prescribed for reducing pain and producing calm sleep without the potential dangers of conventional opiate drugs. It may be useful for painful conditions in which there is irritation or stimulation of afferent pain fibers, in disturbed sleep, and for anxiety.¹⁰⁸ Its medical use as an analgesic and sedative in the United States dates as far back as the late nineteenth century, even being included in the Parke-Davis catalog for these purposes, and as an excellent alternative to morphine without its side effects.^108,211 Today, California poppy is widely used by herbalists in tincture form. Pharmacologic data demonstrate sedative activity in vivo, as well as GABAergic activity, sedative and anxiolytic action, and dose-dependent analgesia (when administered by injection). Two controlled clinical trials, the herb, combined with Corydalis cava, both standardized extracts, demonstrated normalization of disturbed sleep without carryover effects or addiction.¹⁰⁸

Figure 7-6 California poppy (Eschscholzia californica).

Photo by Martin Wall.

Corydalis

The Chinese botanical corydalis, is a strong and reliable analgesic. It is commonly used for headache, lumbar pain, abdominal pain, joint pain, menstrual pain, and other neurologic pain, making it specific for the symptoms associated with CPP. Alcohol and acetic acid extractions are the strongest, although powdered herb is considered effective as well. The mechanism of action of analgesia is thought to be inhibition of the reticular-activating system in the brainstem. Corydalis can increase the pain threshold significantly. Continuous use of corydalis results in tolerance and may theoretically lead to a cross-tolerance to morphine.^212,213 However, from a Chinese medical perspective the effects of corydalis are more than palliative as it is used to help promote pelvic circulation and therefore may treat underlying pelvic congestion. The alkaloids in this herb have sedative and hypnotic effects and act synergistically with barbiturates.²¹² Chinese pharmaceutical companies have produced several preparations from corydalis alkaloids for use as analgesics. The available preparations include a 30-mg tablet containing all alkaloids and a 10% tincture used in doses of 5 mL three times daily.²¹² Overdose leads to muscle relaxation and CNS depression. Corydalis is contraindicated in pregnancy.^32,212,213

Cramp Bark and Black Haw

Cramp bark and black haw were similarly used for the treatment of pelvic pain, particularly of a spasmodic nature, and specifically when accompanied by a sensation of dragging pressure in the groin and drawing pain in the legs.^31,211

Jamaican Dogwood

Jamaican dogwood is a reliable analgesic and spasmolytic herb with mild sedative properties. It was prescribed by the Eclectics for neuralgias, spasmodic complaints, migraines, dysmenorrhea, nervous tension, insomnia, and nervous excitability, although Felter cautioned about potential toxic effects (including convulsions) in large doses.⁹⁹ Ellingwood elaborated on its effects in quieting uterine pains of labor, promoting rest, and having a specifically relaxing influence, in addition to its general analgesic effects. He stated that the herb “acts in close harmony with the vegetable uterine remedies, promoting the influence of Macrotys [Actaea racemosa-black cohosh], the viburnums…pulsatilla and dioscorea among others.”³⁰ The spasmolytic activity of Jamaican dogwood may be attributable to its isoflavone constituents; however, this plant has been only minimally studied.¹⁵⁴ Combined in equal parts with cramp bark or black cohosh, this author has found it a highly effective treatment for gynecologic and pelvic pain of neuromuscular origin, for dysmenorrhea, endometrial pain, urinary tract infection, and other pelvic pain. It also may be used postsurgically as an alternative to conventional pain medications. Regarding its toxicity, it is advisable that the recommended dosage range not be exceeded and that the herb not be used by pregnant women, or patients with bradycardia or cardiac insufficiency.¹⁰⁸

Kava kava

Kava kava has been used traditionally as a muscle relaxant to reduce anxiety and may be considered for the treatment of muscle spasms associated with CPP. Both aqueous and lipid soluble extracts of kava have demonstrated antinociceptive activity through nonopiate receptor mechanisms.¹⁵⁸ It is commonly used by herbalists for the treatment of pain as well as anxiety. (See Plant Profiles: Kava Kava for safety considerations.)

Pulsatilla

Pulsatilla (Fig. 7-7), also called pasque flower, has analgesic and sedative properties. It is listed in the British Herbal Compendium for the treatment of painful spasmodic conditions of the female reproductive systems and dysmenorrhea. It is generally used in tincture form. Fresh herb contains potentially irritant and toxic compounds; therefore, only dried plant should be used, and the herb should not be used during pregnancy. Overdose can lead to gastric irritation, coma, and convulsions; thus, it is essential that patients stay within the proper dosage range, and use be monitored by an experienced practitioner.^25,108 This herb is more commonly prescribed by naturopathic practitioners than herbalists in the United States, although it is also used by European herbalists.

Figure 7-7 Pulsatilla (Anemone pulsatilla).

Photo by Martin Wall.

Black Cohosh, Cramp Bark, and Black Haw

Black cohosh, cramp bark, and black haw are traditionally used as uterine antispasmodics and analgesics, and are discussed throughout this text for these properties (see Dysmenorrhea and Plant Profiles). This three-herb combination administered as a tincture is especially effective for the treatment of pelvic aching and pain. (See Plant Profiles: Black Cohosh for safety considerations with this herb.)

Dong Quai and Peony

Dong quai and peony, in addition to their significant analgesic and spasmolytic actions, are considered herbs that “move blood” and relieve stasis or stagnation in TCM.^92, 214 215 216 The TCM concept of uterine stasis is consistent with the Western concept of pelvic congestion syndrome described in the preceding. Additionally these herbs, often used together in combination, and often with the addition of licorice (Glycyrrhiza glabra or G. uralensis) are considered effective for the treatment of a number of gynecologic conditions that may be involved in the etiology of CPP, such as dysmenorrhea, polycystic ovarian syndrome (PCOS), and uterine fibroids. The Japanese traditional formula TJ-68, Shakuyaku-kanzo-to (Chinese: shao-yao-gan-cao-tang), which contains concentrated white peony root and licorice, has been approved by the Japanese government for clinical use in the treatment of pain and acute muscle spasm, including dysmenorrhea.¹⁰⁸

Marijuana

One herb, not available widely (or at least, legally available) for clinical use that has clinically demonstrated significant uterine antispasmodic and analgesic effects is Cannabis indica, more commonly referred to as marijuana (Fig. 7-8). This controversial medicinal plant and recreationally used herb has a long history of use for relief of uterine spasms and dysmenorrhea, considered by the Eclectics to be a “soothing uterine tonic.”³⁰ In fact, its use is ancient, with references and artifacts of its use found widely in Middle Eastern, Ayurvedic, and Semitic writings, continuing through to its medical use in Europe well into the late nineteenth century for the treatment of a variety of gynecologic and obstetric conditions, not limited to but including dysmenorrhea. A pharmaceutical product from the late nineteenth century, Dysmenine Compound, produced by the Keysall Pharmical Company, Kansas City, MO, contained Cannabis, Cypripedium, Scutellaria, Pulsatilla, Viburnum prunifolium, Caulophyllum, Viburnum opulus, and Capsicum. The compound was indicated for dysmenorrhea, menstrual colic, and cramps.²¹⁷ Indeed, this formula is not very different from one that might be prescribed by herbalists today (see sample formulae in the following); however, minus the now illegal cannabis and the ecologically endangered lady’s slipper orchid (Cypripedium). Although it is not possible given the current legal–medical climate surrounding the use of Cannabis to prescribe this herb clinically, it is worthwhile to note its use and possible beneficial effects, as these have likely not escaped those who manage to procure it for self-medication for the treatment of chronic or cyclic pelvic pain. Russo et al., in Women and Cannabis: Medicine, Science, and Sociology, provide substantial evidence of its use. They cite Grinspoon and Bakalar in their 1993 book Marihuana, the forbidden medicine, who discuss numerous case studies of women using cannabis effectively to treat PMS, menstrual cramps, and labor pain, and when used at low doses, without cognitive impairments. They also cite an Australian study of the uses of cannabis for obstetric and gynecologic complaints in which 51% of respondents indicated use for PMS or dysmenorrhea. Discussing this herb’s appropriate use with patients, outside the context of prescribing or condoning its use, is therefore possibly important and appropriate. The mechanisms of action appear to be primarily through anti-inflammatory activities. An interesting approach for inflammation-mediated pelvic pain is the use of the seeds of the hemp plants, which are notably rich in gamma-linolenic acid, in which women with PMS and dysmenorrhea have found to be low. In one study, a daily dose of 150 to 200 mg of over 12 weeks greatly improved PMS related symptoms; this dose could be provided by a 5-mL daily dose of hemp seed oil.²¹⁷

Figure 7-8 Dysmenine compound—old pharmacy bottle.

Photo by Ethan Russo.

Motherwort

Motherwort (Leonurus cardiaca) is a classic herb for the treatment of pelvic pain. Its actions appear to modulate both relaxant and contractile activity of the uterus, perhaps with an overall effect of regulating a balance between the two for effective uterine muscle activity. The commonly used Western species L. cardiaca has barely been evaluated for its effects in gynecology, whereas Chinese species have been evaluated in several investigations and have been found to have stimulating effects on the myometrium in vivo. The effect on the uterine smooth muscle may be related to alteration of the ion concentration in relation to myoelectric activity, resulting in the increase of myoelectric activity of pace setter cells as well as in the acceleration of depolarization of spike activity.²¹⁸ Leonurine, a plant alkaloid present in Chinese motherwort, has demonstrated some efficacy as a vascular smooth tone inhibitor, possibly through inhibition of Ca²⁺ influx and the release of intracellular Ca²⁺.²¹⁹ It is uncertain whether these findings and effects can be extrapolated to effects on uterine vascular tone. Other studies have demonstrated interesting effects on mediators of the inflammatory and coagulation pathways in relationship to coronary blood flow and alleviation of stasis that may have some correlation to the use of this herb in both TCM and Western herbal medicine to alleviate pelvic congestion (in TCM “blood stasis” or “stagnation”). In one study of 105 patients, 94.5% showed improvements in reduction in blood viscosity and fibrinogen content, important both for healthy blood flow but also in the prevention of release of inflammatory compounds associated with clot formation.²²⁰ A Russian study reported on the soporific activity of a combination of equal parts of valerian, motherwort, and hawthorn (Crataegus spp.) in tincture form. This combination prolonged the soporific effect of sodium ethaminal.²²¹ The effects of motherwort (L. cardiaca) for the treatment of spasmodic uterine pain and pelvic congestion are predicated on historical and contemporary clinical use, for which it remains a popular choice in gynecologic formulae.

Antidepressants and Anxiolytics

Herbs of note that possess both antidepressant or anxiolytic activity, as well as analgesic or antispasmodic activity, include St. John’s wort, kava kava, motherwort, and ashwagandha, the latter of which is also a respected adaptogen and whose analgesic effects are discussed elsewhere in this text (see Plant Profiles). Gentle nervines that are commonly used as adjunct teas in the treatment of mild depression include chamomile, lemon balm, and lavender. Lavender also may be used externally in baths for its soothing aromatherapeutic effects, as well as for mild topical analgesia for the vulva.

Adaptogens

The use of adaptogens in the treatment of CPP is primarily for the reduction of stress and anxiety, modulation of inflammation, and improvement of sleep disorders. They are part of a long-term treatment plan rather than quick-acting for specific symptoms (see Chapter 6 and Plant Profiles). Ashwagandha has specific analgesic activity, and is among the most specific of choices for CPP.

Anti-inflammatories

Uterine Tonics: Venotonics

Treatment of pelvic congestion syndrome incorporates a combination of therapeutic actions, including anti-inflammatory, uterine tonics, and herbs used as vascular tonics. Uterine tonics, which historically have included herbs such as blue cohosh, goldenseal, lady’s mantle, motherwort, partridge berry, red raspberry leaf, and cramp bark and black haw, are thought to exert their efforts by improving the overall tone of the uterine smooth musculature and vasculature. Goldenseal, for example, typically regarded for its antimicrobial effects, was used extensively by the Eclectics for the treatment of uterine bleeding resulting from a variety of conditions, including endometriosis, fibroids, and changes associated with menopause.²¹¹ Although no clinical studies have been conducted using whole herb, in vitro trials using berberine, one of the primary alkaloids in goldenseal, have demonstrated both uterine smooth muscles stimulant and inhibitory activity.²² Aqueous extracts of red raspberry leaf also have demonstrated both stimulatory and inhibitory effects on uterine smooth muscle.¹⁰⁸ In fact, this paradoxic effect is seen with several of the herbs commonly used as both uterine tonics and spasmolytics, for example, cramp bark and black haw. It is thought that the effect of these dual activities is a normalization of uterine activity, and the promotion of smooth, nonspasmodic uterine muscle activity, thus improving tone and reducing pain.^222,223

Several herbs with venotonic activity should be considered for the treatment of pelvic congestion in CPP. Most notable are blue cohosh and horse chestnut. Blue cohosh has demonstrated uterine tonic, vasoconstrictive activity, and continues to be used for the treatment of many gynecologic formulae in which a uterine tonic is required. Historically, it has been used for labor induction, amenorrhea, dysmenorrhea, menorrhagia, and to induce abortion.^195,224 Blue cohosh is listed in the British Herbal Pharmacopoeia (1983) as a spasmolytic and emmenagogue.²²⁵ It also may be used as an ovarian tonic and for the treatment of a variety of menstrual complaints, including menorrhagia, amenorrhea, dysmenorrhea, and pelvic congestion syndrome.⁸ Horse chestnut is used to improve circulation through vascular tonification, to improve venous tone in venous insufficiency, and for the relief of aching discomfort in the lower limbs associated with varicosities and for complaints associated with chronic venous insufficiency (CVI).^22,100,157 Traditionally, it was used in the treatment of neuralgia and “conditions of venous congestion particularly with dull, aching pain and fullness.”²² One studied demonstrated safe use for 56 months without harmful effects. Horse chestnut extract is the third most widely sold herbal product in Germany, where it is used long-term in clinical practice apparently without adverse effects.¹⁰⁰ There appears to be very low risk associated with proper administration, although it is recommended that only product standardized to its presumed active ingredient, escin (aescin) be used, and not to exceed 12 weeks at recommended doses.¹⁵⁷ Adverse effects from use of horse chestnut seed extract have included GI upset and calf spasm most commonly, with headache, nausea, and pruritus occurring less commonly. Overall, adverse effects are extremely rare, in an observational study occurring at a rate of less than 0.6% in more than 5000 subjects.

Muscle Relaxation and Re-education, Biofeedback, and Electrical Stimulation

Muscle tension in the pelvis, hips, and lower back may be caused by, or lead to CPP. Helping a woman to identify

and relax tension, become aware of and adjust her body mechanics and standing and sitting posture, and wear appropriate shoes to minimize postural problems can help to reduce pain caused by structural imbalances. Pelvic relaxation training techniques should be taught and practiced regularly. Much of this can be done at home, but physical therapy can be helpful if there is limited joint movement or muscular problems. Prolonged sitting or standing can aggravate CPP, so patients may need suggestions and supportive counseling for modifying jobs or activities that require positions that exacerbate the problem. Exercises such as running or high-impact aerobics also may be aggravating, and should be replaced with gentler, relaxing forms of exercise, for example, walking, tai chi, yoga, or dance.²²⁶ Physical therapy for the treatment of musculoskeletal problems or postural problems can be beneficial for women with CPP.²²⁷

Biofeedback machines can be effective in helping women to identify and improve the effectiveness of pelvic muscle relaxation techniques for acquired muscle tension. The woman is instructed to visualize and practice muscle relaxation techniques while using a biofeedback device for feedback on the relaxation efforts.

Electrical stimulation using vaginal, rectal, or surface electrodes is used to produce rhythmic contraction and relaxation of the pelvic floor muscles. Electrical stimulation may give immediate reduction in the level of pain early in treatment, restore more normal muscle activity patterns over time, and also may help to disperse inflammatory mediators caused by chronic muscle spasm. 228 229 230

Uterine Displacement–Mayan Uterine Massage

It has been suggested that uterine retrodisplacement can lead to symptoms of CPP.¹⁹⁸ Although the role of pelvic tension and improper posture in the etiology of CPP is accepted, conventional medicine does not address the potential for uterine displacement, other than prolapse associated with pelvic relaxation as an etiologic factor. Mayan uterine massage is a practice introduced into the United States by Rosita Arviga, after dedicated study with a Belizean shaman who specialized in this technique. Ms. Arviga trains and certifies people in this technique and it has grown in popularity because of many anecdotal reports of success for the treatment of vague but sometimes debilitating complaints such as CPP, as well as for many other gynecologic problems. The treatment is predicated on the belief that uterine displacement, which may occur as a result of childbearing, poor posture, sedentary lifestyle, improper carrying and work habits, etc., can lead to significant pelvic congestion, gynecologic, nervous, circulatory, and digestive problems. No studies have been done to objectively demonstrate efficacy. The practice appears generally noninvasive (it is an intervention); however, it should not be used for pregnant women.