Endometriosis

2011

Endometriosis is one of the most common gynecologic problems in the United States and a leading gynecologic cause of both hospitalization and hysterectomy. Women with symptomatic endometriosis face chronic and sometimes debilitating pain; asymptomatic and symptomatic women alike may experience significant fertility problems due to this condition. The least-biased estimate for the overall prevalence of endometriosis in reproductive-age women is about 10%. Endometriosis is defined as the presence and growth of endometrial tissue in locations outside of the uterus. These cells may appear on the ovaries, fallopian tubes, bowel, bladder, peritoneal tissue, ligaments, or other structures in the abdominal cavity, and rarely may occur at other sites, including the nasal and respiratory passages leading to nosebleeds or pink frothy sputum at the time of the menses. Displaced endometrial tissue responds to cyclic hormonal changes, proliferating and shedding outside of the uterus. The bleeding is accompanied by inflammation caused by irritation of local tissue, such as, the peritoneum. Recurrent inflammation can cause scarring and adhesions that can cause pain and dysfunction of other affected sites. Endometriosis is common in women between menarche and menopause, and is associated with as many as 25% of cases of infertility; however, causality has not been definitively established.

Endometriosis occurs across all socioeconomic and ethnic populations, is more common in women who experience early menstruation and fewer than two pregnancies, is associated with menstrual cycle length greater than 30 days, and is more prevalent in women with IUD use greater than 2 years (Box Risk Factors for Endometriosis). Studies demonstrate that women who have experienced repeated vaginal and uterine infections have higher rates of endometriosis than the general population. Women with a mother or sister with endometriosis are more likely to suffer from severe endometriosis, suggesting a genetic predisposition; however, milder forms do not always have familial association. The literature is conflicting on the relationship between oral contraceptive (OC) use and the risk of endometriosis. A 1993 review by Vercellini et al. showed that four prospective investigations found a nonsignificant reduction in risk of up to 20%. Of three case control studies, two suggested an increased risk and one indicated a reduced risk of developing endometriosis with oral contraceptive use. The 1994 analysis of the Oxford Family Planning Association oral contraceptive study found a significantly reduced risk of endometriosis in current oral contraceptive users. The researchers found that oral contraceptives were associated with a 60% reduction in endometriosis. The risk of endometriosis was significantly related to age with the highest risk occurring at ages 40 to 44 years when compared with women ages 25 to 29 years. On the other hand, the risk of endometriosis was elevated among women who formerly used the pill by almost twice the rate of women who had never used oral contraceptives.

Risk Factors for Endometriosis
Possible Risk Factors
Early menarche (before age 12)
Cycles <26 days (= higher frequency)
Heavy bleeds >7 days
IUD use
D&C history
Fewer than two pregnancies
Family history
High stress, especially linked to relationships or sexuality
High fat intake, especially heated fats, fried foods
Risk Reducing Factors
Full-term pregnancies
Breastfeeding
Avoiding caffeine, alcohol
Regular exercise (timing and type are important)

Multiple theories exist on the etiology of this condition, including retrograde menstrual flow, lymphatic flow theory, and de novo origin. In fact, Konickx et al. propose that mild endometriotic lesions are common and to some extent normal at varying times in all women, and that it is symptomatic, aggressive, or deeply infiltrating endometriosis that should be considered a disease. Retrograde menstrual flow theory describes menstrual or endometrial tissue flowing backward through the fallopian tubes and into the abdominal cavity. Lymphatic flow theory suggests the spread of endometrial tissue throughout the body via the lymphatic system. Some researchers postulate that coelomic metaplasia, a de novo origin, might be induced by pathologic processes as a result of chemical exposure. A role for oxidative stress has also been suggested as one of the contributing factors for the development of endometriosis, possibly as part of a conglomeration of factors that pair immunologic and inflammatory factors in its etiology.

There is substantial evidence that immunologic factors play a role in the pathogenesis of endometriosis and endometriosis-associated infertility, and that there is a bidirectional relationship between the endocrine and immune systems. In early endometriosis, elevated levels of inflammatory mediators such as cytokines, lymphocytes, and macrophages can be identified in the peritoneal fluid. Immune alterations include increased number and activation of peritoneal macrophages, decreased T-cell reactivity and natural killer cell cytotoxicity, increased circulating antibodies, the presence of autoantibodies, and changes in the cytokine network. Decreased natural killer cell cytotoxicity leads to an increased likelihood of implantation of endometriotic tissue. In addition, macrophages and a complex network of locally produced cytokines modulate the growth and inflammatory behavior of ectopic endometrial implants. There also may be a positive correlation between immunosuppression and disease progression in the presence of established disease. Further, women with endometriosis appear to have higher rates of atopic conditions and susceptibility to opportunistic infections (e.g., candidiasis) than women who do not have endometriosis.

Environmental exposures appear to play a certain role in the development of endometriosis via endocrine disruption. Studies demonstrate a link between dioxin exposure and the disease, with increased dioxin-like compounds found in the serum of women with peritoneal endometriosis and deep endometriotic (adenomyotic) nodules. A search of the BIOSIS database for endometriosis and dioxin yielded over 50 studies. The development of this condition is likely a result of the interplay of numerous factors; thus, it has been concluded by many researchers that endometriosis is, most likely, a condition with complex multifactorial origins.

Symptoms

The following symptoms (Box Common Symptoms of Endometriosis), 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.) Other causes of pelvic and abdominal pain or bleeding must be ruled out.

Common Symptoms of Endometriosis
Abdominal pain
Back pain
Depression
Frequent or constant pain that is over site
Infertility
Insomnia, lethargy
Later on, pinched nerve pain
Ovulation pain
Pain on intercourse
Pain with bowel movement or urination
Pelvic burning, aching not limited to menstruation
PMS with dysmenorrhea and infertility
Rarely, bleeding after bowel movements or after intercourse
Referred pain in distant sites, especially shoulder blades or top of collar bone
Swollen abdomen, intestinal gas

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. 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. Endometriosis is staged based on the location(s) of the endometrial tissue as follows:

• Stage I, or minimal, disease (superficial endometriosis, filmy adhesions)

• Stage II, or mild, disease (superficial and deep endometriosis, filmy adhesions)

• Stage III, or moderate, disease (superficial and deep endometriosis, filmy and dense adhesions)

• Stage IV, or severe, disease (superficial and deep endometriosis, dense adhesions)

Endometriosis: Conventional Treatment Approaches

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 Botanical Treatment Strategies for Endometriosis). 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.

Botanical Treatment Strategies for Endometriosis

Therapeutic Goal Therapeutic Activity Botanical Name Common Name
Pain relief Analgesics

Anodynes

Sedatives

Anemone pulsatilla Pulsatilla
Angelica sinensis Dong quai
Actaea racemosa Black cohosh
Corydalis ambigua Corydalis
Eschscholzia califomica California poppy
Matricaria recutita Chamomile
Paeonia lactiflora White peony
Piper methysticum Kava kava
Piscidea piscipula |amaican dogwood
Pain relief Anti-inflammatory Angelica sinensis Dong quai
Calendula officinalis Calendula
Camellia chinensis Green tea
Echinacea spp. Echinacea
Clycyrrhiza officinale Licorice
Hypericum perforatum St. John’s wort
Matricaria recutita Chamomile
Oenothera biennis Evening primrose
Paeonia lactiflora White peony
Prunus cerasus Cherry
Rehmannia glutinosa Rehmannia
Tanacetum parthenium Feverfew
Zingiber officinale Ginger
Pain relief Antispasmodics Dioscorea villosa Wld yam
Actaea racemosa Black cohosh
Matricaria recutita Chamomile
Paeonia lactiflora White peony
Viburnum opulus Cramp bark
Viburnum prunifolium Black haw
Zingiber officinale Ginger
Immunologic support, reduction in fatigue, depression and concomitant psycho-emotional symptoms Immunostimulatory herbs

Adaptogens

Angelica sinensis Dong quai
Astragalus membranaceus Astragalus
Calendula officinalis Calendula
Cordyceps sinensis Cordyceps
Echinacea spp. Echinacea
Eleutherococcus senticosus Eleuthero
Panax ginseng Ginseng
Panax quinquefolius American ginseng
Picrorrhiza kurrhoa Picrorrhiza
Rhaponticum carthimoides Rhaponticum
Rhodiola rosea Rhodiola
Schisandra chinensis Schisandra
Thuja arbor-vitae Thuja
Withania somnifera Ashwagandha
Improve pelvic circulation and tone; reduce size and extent of endometriotic tissue Emmenagogues

Uterotonic herbs

Achillea millefolium Yarrow
Alchemilla vulgaris Lady’s mantle
Caulophyllum thalictroides Blue cohosh
Hormonal regulation: Indirect via enhanced clearance of estrogen by liver and bowel, improved hormone metabolism by liver, improvement of healthy hepatic function Hepatic trophorestoratives

Aperients

Cholagogues

Hepatics

Calendula officinalis Calendula
Chionanthus virginicus Fringe tree
Curcuma longa Tumeric
Rosmarinus officinalis Rosemary
Schisandra chinensis Schisandra
Silybum marianum Milk thistle
Taraxacum officinale Dandelion
Hormonal regulation:Direct via known or putative hormonal actions Hormonal regulators Cossypium herbaceum Cotton root
Verbena officinalis Blue vervain
Vitex agnus-castus Chaste tree
Improve pelvic and abdominal lymphatic circulation; enhance immunologic function Lymphatics Calendula officinalis Calendula
Stress relief Nervines Leonurus cardiaca Motherwort
Verbena officinalis Blue vervain

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 traditional Chinese medicine 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):

• Estrogen excess

• Progesterone deficiency

Magnesium deficiency

• Essential fatty acid deficiency

• High stress (often complicated by hypoglycemia)

• Hormone imbalance other than progesterone / estrogen ratio

• Excess dietary caffeine

• Excess alcohol consumption

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

Formulae for Dysmenorrhea

Formula for Treatment of Mild to Moderate Pain Associated with Dysmenorrhea

Black cohosh (Actaea racemosa) 20 mL
Cramp bark (Viburnum opulus) 20 mL
Chamomile (Matricaria recutita) 15 mL
Dong quai (Angelica sinensis) 15 mL
Wild yam (Dioscorea villosa) 15 mL
Licorice (Glycyrrhiza glabra) 10 mL
Ginger (Zingiber officinale) 5 mL

Total: 100 mL

Dose: 2.5 to 4 mL every 2 to 4 hours during episodes of endometrial discomfort. This can also be given 3 mL three times daily prophylactically for women who experience predictable cyclic pain associated with endometriosis.

Formula for Treatment of Moderate to Severe Pain Associated with Dysmenorrhea

Black cohosh (Actaea racemosa) 25 mL
Cramp bark (Viburnum opulus) 25 mL
Wild yam (Dioscorea villosa) 20 mL
Corydalis (Corydalis ambigua) 15 mL
Jamaican dogwood (Piscidea piscipula) 15 mL

Total: 100 mL

Dose: For severe acute pain take 2.5 mL every 15 minutes until pain begins to subside, or for up to 2 hours consecutively, then reduce dose to 2.5 to 5 mL every 2 to 4 hours as needed.

Sedative Formula for Severe Pain Associated with Endometriosis

Cramp bark (Viburnum opulus)
California poppy (Eschscholzia californica)
Jamaican dogwood (Piscidea piscipula)

Dose: Combine equal parts of the above liquid extracts and take 2.5 mL every 15 minutes for 1 hour to induce sleep.

Endometriosis: Discussion Of Botanicals

Case Histories: Endometriosis

Endometriosis Patient #1

Lori, 35, is a highly stressed lawyer who smokes and experiences moderate to severe pain associated with endometriosis. She plans to quit smoking as soon as she gets a new job, marries, and moves this year. She hopes to have children soon after.

Tincture Formula I (ovulation through end of menses)

Chaste berry (Vitex agnus-castus) 12.5 mL
Black haw (Viburnum prunifolium) 25.5 mL
Blue vervain (Verbena officinalis) 25.5 mL
Yarrow (Achillea millefolium) 12.5 mL
Milky oats (Avena sativa) 12.5 mL
Corydalis (Corydalis ambigua) 12.5 mL

Total: 100 mL

Dose: 5 mL diluted in ¼ cup water tid.

Tincture Formula II (end of menses to ovulation)

Chaste berry (Vitex agnus-castus) 25 mL
Calendula (Calendula officinalis) 12.5 mL
White peony (Paeonia lactiflora) 20 mL
St. John’s wort (Hypericum perforatum) 30 mL
Partridge Berry (Mitchella repens) 12.5 mL

Total: 100 mL

Dose: 5 mL diluted in ¼ cup water tid.

Endometriosis Patient #2

Karen is a 21-year-old with no previous history of reproductive problems. After acute abdominal pain she was diagnosed with endometriosis by ultrasound, but decided against medication or surgery. She has abdominal pain and bloating, with spotting and heavy menstruation.

Tincture Formula I (ovulation through end of menses)

Chaste berry (Vitex agnus-castus) 12.5 mL
Cramp bark (Viburnum opulus) 25 mL
Blue vervain (Verbena officinalis) 25.5 mL
Ashwagandha (Withania somnifera) 25 mL
Black cohosh (Actaea racemosa) 12.5 mL

Total: 100 mL Dose: 5 mL diluted in ¼ cup water tid.

Tincture Formula II (end of menses to ovulation)

Chaste berry (Vitex agnus-castus) 20 mL
Blue Cohosh (Caulophyllum thalictroides) 10 mL
Sarsaparilla (Smilax ornate) 10 mL
Milk Thistle (Carduus marianus) 20 mL
Partridge Berry (Mitchella repens) 10 mL
Wild Yam (Dioscorea villosa) 20 mL
Valerian (Valeriana officinalis) 10 mL

Total: 100 mL

Dose: 5 mL diluted in ¼ cup water tid.

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.

Choose Between [When taking fatty acid supplements, it is important to increase antioxidant intake]:

Evening primrose oil: 3 g / day (may be cost prohibitive to some)

Omega-3: 600 mg EPA

Flax oil: 1/8 tsp to 1 tbl daily

Flax seed oil starting at 1/8 tsp doses, up to 1 tsp per dose or more as individuals can tolerate.

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

Additional Therapies

Lifestyle Management

Provide counseling to address psychosocial issues; suggest stress reduction techniques (e.g., yoga, meditation, counseling, visualization).

Exercise

Regular exercise, such as yoga, to reduce pelvic tension and improve suppleness, as well as relieve general tension and fatigue, should be encouraged.

Treatment Summary for Endometriosis

• Improve nonspecific immunity with adaptogens, immunomodulators.

• Reduce inflammation.

• Improve organ and tissue health where possible using uterine tonics.

• Decrease exposure to xenoestrogens.

• Decrease relative excess of estrogen.

• Increase liver function for hormone metabolism, from cholesterol synthesis to steroidal catabolism.

• Manage pain using antispasmodics.