Etiologic Theories

Retrograde flow, the predominant theory first proposed in 1927, suggests that during menses blood flows backward and provides seeds of implants in the pelvic cavity. The problem with this theory is that more than 90% of menstruating women without endometriosis have retrograde flow; thus, this theory was challenged and questions were raised as to the biochemical and immunologic factors causing the implantation of endometrial tissue within the pelvic environment.¹ Some theories are based on findings that endometrial implants from women with endometriosis are biochemically different from those from normal women.²

Other findings suggest that cells may implant only in women with altered cell immunity.¹ Implants found in odd locations, such as the nose and lungs, suggest the transportation of endometrial tissue through lymphatic channels and blood vessels. Some researchers believe the implants to be of embryologic origin, when pieces of the uterus were left behind during development, and that these implants, when activated, secrete a chemical causing the nearby capillaries to bleed.³

Other research on endometriosis in baboons suggests activation by environmental toxins that mimic estrogens.⁴ Exposure to radiation and dioxin has been associated with a higher frequency of endometriosis.^5,6 The highest incidence of endometriosis appears to be in Belgium, which is also the home to the highest level of dioxin pollution in the world.⁷

Two studies, however, one in Belgium, found no significantly increased risk with dioxins or polychlorinated biphenyls.⁸ The other study, in Italy, found no significantly increased risk of endometriosis in women who had high levels of dioxin in their blood.⁹ Although there is currently no definitive epidemiologic evidence linking any one class of chemicals to the risk of endometriosis, there does appear to be some suggestion of a link with estrogen-like compounds in the environment,¹⁰ called xenoestrogens, which can disrupt estrogen and estrogen metabolism. Substances that have been shown to have estrogenic effects in the body include PCBs, weed killers, liners in tin cans, plastics, detergents, and household cleaners.¹¹

Immunologic alterations may exist in women with endometriosis. Increasingly, we are finding evidence that a lack of proper immune surveillance in the pelvic area is the cause of endometriosis and that impairment in other aspects of the immune system function are involved in the progression of the disease.¹²

Women with endometriosis have been found to have suppressed natural killer cell activity in their peritoneal fluid,^13,14 high levels of immunoglobulins IgG and IgM,¹⁵ and high levels of autoantibodies against ovary and endometrial cells.^16,17

Both types of immunity, cell-mediated and humoral, have been implicated in endometriosis, with immunologic defects present even in the mildest forms of the disease.¹⁸ Macrophages are found in greater numbers in the early stages of endometriosis.¹⁹

Cytokines, macrophages, T lymphocytes, and tumor necrosis factors have all been found to be increased in the peritoneal fluid in women with endometriosis,^20–22 and their increase correlates with the severity of the disease. Growth factors, angiogenic factors, and lipid peroxidation in the peritoneal fluid may stimulate endometrial cell growth. Targeting of these proinflammatory compounds and blocking their action with antioxidants and other compounds provide a good rationale for new treatment strategies, both conventional and with natural compounds.

Genetic influences the area also likely involved in endometriosis. Grouping of endometriosis within families has been found in clinical studies,^23,24 populations-based studies,²⁵ and even studies of twins.^26–28 Several abnormalities in detoxification enzymes, tumor suppressor genes, and other genetic factors occurring in multistep fashion may be involved both in the development and the progression of the disease.²⁹

Diet

Several dietary principles are key in a natural medicine approach to endometriosis:

The consumption of trans fats appears to increase the risk of endometriosis, whereas long-chain omega-3 fats appear to be protective. Twelve years of prospective data from the Nurses’ Health Study II, which began in 1989, weres analyzed for dietary fat and its association with many health problems, including endometriosis.³² Although there was no association with total fat consumption and endometriosis risk, those women with the highest consumption of long-chain omega-3 fatty acids were 22% less likely to be diagnosed with endometriosis compared with women who had the lowest intake of these fats. Those women who had the highest intake of trans unsaturated fats were 48% more likely to be diagnosed with endometriosis.

Foods high in fiber are associated with optimal transit time in the intestines and an optimal balance of friendly microorganisms within the large intestines (see Chapter 52). These microorganisms, better known as gut flora, crowd out the other types of flora that deconjugate estrogens and allow estrogens to recycle back through the body. Studies suggest that a predominantly vegetarian diet emphasizing less protein and more fiber can lead to a decrease of biologically active unconjugated estrogens in the blood plasma.³³ Although higher-protein diets are found to provide enzymes for the detoxification pathways of estradiol,³⁴ vegetarian diets are of greater value owing to their lower fat content. Diets containing large amounts of animal protein, especially in the form of red meat, contain large amounts of arachidonic acid, which promotes inflammatory prostaglandins and thus inflammation and pain. By adding vegetable protein, soy, nut butters such as almond, and salmon to our diets, we tip the inflammatory pathway toward antiinflammatory prostaglandins that inhibit tumor growth—and possibly endometrial growth.

By increasing the intake of vegetables, specifically those that enhance liver function, cell damage from toxins and metabolites is prevented. “Liver foods” to be increased include carrots, beets, and cabbage-family vegetables, owing to their role in aiding phase 2 of the liver’s detoxification pathway. Indole-3-carbinol—found in broccoli, Brussels sprouts, cabbage, and cauliflower—favors the less active metabolite of estrogen.³⁵ Other liver-cleansing foods are carrots, artichokes, lemons, dandelion greens, watercress, and burdock root. Onions, garlic, and leeks contain organosulfur compounds, which enhance the immune system and induce enzymes that detoxify in the liver. In addition, they contain the bioflavonoid quercetin, which is known to stimulate the immune response, protect against oxidation, block the inflammatory response, and inhibit tumor growth.³⁶ Organically grown vegetables are expected to contain lower levels of pesticides that may also mimic estrogen.

The isoflavones in soy products and the lignans in flax seeds may also be important in a dietary approach to endometriosis. Many people might claim that these phytoestrogen compounds should be avoided, thinking that they would stimulate the growth of endometriotic implants, much as estrogen might. However, the evidence supports the inclusion of soy in the diets of women with endometriosis. A Japanese study demonstrated that a moderate intake of soy isoflavones was associated with a decreased risk of premenopausal hysterectomy. Because some of the surgeries involved endometriosis, these results led the authors to conclude that moderate soy intake may decrease the risk for endometriosis.³⁷

Seasonings such as turmeric (curcumin) protect against environmental carcinogens, decrease inflammation, and increase bile secretion. Adding a tablespoon of milk thistle seeds that have been soaked and ground can also help with liver function. Fresh flax seeds increase antiinflammatory fatty acids. Seasoning with Fucus (a seaweed) helps to stimulate T-cell production and absorb toxins.³⁸

Foods to decrease include sugar, caffeine, dairy, red meat, and alcohol. Sugar is known to increase estrogen levels in males.³⁹ A study of 50 women with endometriosis examined the effect of the reduction of higher glycemic carbohydrates, the addition of omega-3 and omega-9 fatty acids, and the elimination of foods containing caffeine and tyramine; after 8 weeks, there was a significant reduction in symptoms.⁴⁰ Endometriosis is found to be specifically correlated with caffeine consumption. Women consuming 5 to 7 g of caffeine monthly had a 1.2-times greater incidence of endometriosis, whereas those consuming more than 7 g had a 1.6-times greater increase.⁴¹ The Environmental Protection Agency estimates that 90% of human dioxin exposure is through food, primarily meat and dairy products.⁴² Cheese, particularly cottage cheese, and milk cause the lipid pathway to be tipped toward prostaglandins and leukotrienes, which cause inflammation, smooth muscle contraction, and vascular constriction. Alcohol consumption depletes stores of B vitamins in the liver and slows the metabolism of estrogen.