Notes from Mary Lou

ENDOMETRIOSIS: A NEW PICTURE OF THE DISEASE IS EMERGING

(read the previous article, "Facts and Figures on Endometriosis")

Endometriosis is a puzzling disease affecting an estimated five million women in the United States. It is a nightmare of misinformation, myths, taboos, lack of diagnosis, and problematic hit-and-miss treatments overlaid on a painful, chronic, stubborn disease.

Endometriosis affects all races, personalities, and socioeconomic groups as well as all ages of women, from girls as young as 10 or 11 to women in their 60's and 70's.¹ The terrible impact on young women is evident in the dramatic 250% increase in hysterectomies for endometriosis for women aged 15 to 24 between 1965 and 1984. The same period saw an increase of 186% for women aged 25 to 34.²

Endometriosis now affects an estimated 5 million women in the United States. But before 1921 there were only 20 reports on this disease in the world literature.3 The Endometriosis Association has been systematically studying all aspects of the health and experience of women with endometriosis, listening to the stories of hundreds of thousands of women with the disease, and publishing reports based on our studies in medical journals. It appears that what we call "endometriosis" is just the tip of the iceberg for a whole range of health problems that have underlying them hormonal/immune dysregulation. The type of endometriosis that I am describing is the most severe form of the disease, tends to occur in families with endometriosis and a host of related health problems, and tends to cause numerous health, work, financial, marital and social problems.⁴

In the new picture of the disease which is emerging, one sees not only the traditional symptoms of endometriosis -- chronic pelvic pain, pain with sex, gastrointestinal and bladder problems, infertility, and others -- but also high rates of atopic (allergic) diseases in these individuals and their families including allergies, food intolerances, asthma, eczema, and sometimes debilitating sensitivities to environmental chemicals such as perfumes, cigarette smoke, cleaning agents and others;^5,6 a tendency to infections and mononucleosis;^1,7 problems with Candida albicans;6 mitral valve prolapse;^7,8 fibromyalgia⁹ and chronic fatigue immune dysfunction syndrome;¹⁰ and a greater risk for autoimmune disorders including lupus¹¹ and Hashimoto's thyroiditis.¹²

Endometriosis is a disease of menstruating animals, and primate studies are critical to our understanding of the disease. Aware of the many immune system problems of our members and knowing that U.S. Air Force studies have now shown quite convincingly that radiation exposure of certain types and amounts leads to endometriosis in female rhesus monkeys,^13,14 we set out in 1991 and early 1992 to track down a rumor that rhesus monkeys that had been exposed to PCBs developed severe endometriosis. We learned that indeed there was such a colony which had been studied by the branch of the Canadian federal government in charge of food safety. And indeed, an unusually severe form of endometriosis had been documented in some of the PCB-exposed monkeys: several animals had apparently died from intestinal obstruction caused by extensive disease. Reproductive outcomes from the PCB-exposed animals were poor.^15,16

(c) 1998 Endometriosis Association, Inc.

From the investigator, we learned that there was another colony of rhesus monkeys in which two animals had died of endometriosis. This colony had been part of a toxicology study to evaluate long-term effects of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Groups of eight animals received either 25 parts per trillion (ppt; high dose) or 5 ppt dioxin (low dose); control monkeys were not exposed to dioxin.

At the time we learned of these animals, the original research team had disbanded. The university where the monkeys are housed began selling them -- but had not yet shipped them. An emergency board meeting of the Endometriosis Association was called and we decided to fund the colony for two months and carry out laparoscopies on the entire colony to determine if endometriosis was present in the remaining animals. We brought in one of the leading experts in our field on the appearances of endometriosis, and also a leading authority on the immunology of endometriosis. At the end of a long day of laparoscopies, when the code was broken, the investigators were astounded by the highly statistically significant results: 79% of the animals exposed to dioxin in the study developed endometriosis. Moreover, the disease increased in severity in direct proportion to the level of dioxin exposure -- the more dioxin, the more severe the disease. The dose-dependent relationship was highly statistically significant (p<0.001 using the American Fertility Society and revised AFS classifications).¹⁷

We proceeded with immunological studies with the colony, examining production of interleukin-6 and tumor necrosis factor [important substances secreted by cells in the immune system]. Again, significant results suggested that endometriosis in these animals was associated with immune dysfunction.¹⁸

Since the dioxin results were published, more than a dozen related studies have been launched in research institutions worldwide. Most notably, the National Institute of Environmental Health Sciences and the Endometriosis Association are carrying out a joint study to determine blood levels of dioxin, furans, and PCBs in women with endometriosis. The Environmental Protection Agency has carried out studies to determine the effects of dioxin on endometriosis in a rodent model.^18,19,20 Several animal studies and human endometrial cell culture lines have also shown dioxin causes development of endometriosis. Many of these studies are nearing publication. Far from assuaging fears over endocrine disruptors and endometriosis, the new studies deepen alarm.^{19,20,21,22,23,24,25} The time for action is now.

There is currently no medical treatment for removing dioxin and related compounds from our bodies. Dioxin persists for at least 14 years following exposure. In our rhesus colony, the monkey mothers passed 20% of their body burden of dioxin to their offspring via in utero exposure and by breastfeeding. The newborn offspring were exposed to more dioxin per kilogram of weight than the mothers had themselves received in the experiment.

PCBs are a life sentence, according to some toxicologists: what we don't dump into our children, we will take with us to the grave. Toxicologist Wayland Swain estimates that it may take six generations before PCBs are cleared from our bodies, even with no further exposure. (This work was calculated on the basis of the first mother in the six generations having the average level of PCBs in her breast milk currently found in Michigan mothers who consume PCB-contaminated fish.)²⁶

Because no treatment exists to remove these toxins from our bodies, we must concentrate on effective prevention -- which means regulation of these compounds before they enter our environment. National policy must be set that allows us to identify and eliminate these toxic substances. The EPA's current reassessment of dioxin, in itself a monumental work, is bringing home to Americans the enormity of the task that now awaits us.

Clearly, it is time to look beyond the cancer paradigm. The recent plethora of studies on the endocrine disrupting abilities of these compounds and the EPA reassessment have made it absolutely clear that even low levels of dioxins exert multiple and drastic effects upon the endocrine system and the immune system -- and that the most sensitive biological system may be the developing fetus.

Perhaps even more frightening than the rising incidence of hormonal/immunologic disease is the knowledge that these compounds are being passed along, both in animals and humans, to our offspring. Women with endometriosis face the horrible prospect of passing ever more debilitating forms of this disease on to succeeding generations.

On behalf of the millions of American girls, women, and families, as well as millions more around the world whose lives have been darkened by endometriosis, we urge regulators to implement new policy as soon as possible to rigorously eliminate these toxic substances from our environment.

Thank you for your consideration of these comments.

For further information, contact: Mary Lou Ballweg, President/Executive Director, International Headquarters, 8585 N. 76th Place, Milwaukee, Wisconsin 53223, USA. Telephone: (414) 355-2200. Web site: http://www.endometriosisassn.org

REFERENCES

1. Data from Endometriosis Association Research Registry, partially published in Endometriosis Association Newsletter 10:2, 1989
2. Hysterectomies in the United States, 1965-84. Vital and Health Statistics, U.S. Dept of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Health Statistics, Series 13, No. 92, 1987
3. Older J. "Leeches and Laudanum: Grandmother and You: Historical Highlights." Endometriosis. (New York: Scribners, 1984)
4. Lamb K, Hoffmann RG, Nichols TR. "Family Trait Analysis: A Case-Control Study of 43 Women with Endometriosis and Their Best Friends." American Journal of Obstetrics and Gynecology 154: 3, pp. 596-601, March 1986
5. Nichols TR, Lamb K, Arkins JA. "The Association of Atopic Diseases with Endometriosis." Annals of Allergy 59:11, November 1987
6. Lamb K, Nichols TR. "Endometriosis: A Comparison of Associated Disease Histories." American Journal of Preventive Medicine 2:6, 1986
7. Ballweg ML. "A Heart Defect in Endometriosis: Another Clue to a Bigger Picture?" Overcoming Endometriosis: New Help from the Endometriosis Association. (New York: Congdon & Weed, Inc. 1987) pp. 228-231
8. Fletcher N. "Mitral Valve Prolapse." Endometriosis Association Newsletter 13:2, 1992
9. Ballweg ML. "Fibromyalgia/Endometriosis Link?..." Endometriosis Association Newsletter 12:3, 1991
10. Ballweg ML. "The Endometriosis- Candidiasis Link." Overcoming Endometriosis: New Help from the Endometriosis Association. (New York: Congdon & Weed, Inc., 1987), pp.198-219
11. Grimes DA, Lebolt SA, Grimes KRT, and Wingo PA: "Two-fold risk of endometriosis in hospitalized patients with lupus." American Journal of Obstetrics and Gynecology 153: 179, 1985
12. Brush MG, Department of Gynaecology, St. Thomas Hospital Medical School, London: "Increased Incidence of Thyroid Autoimmune Problems in Women with Endometriosis." Endometriosis: A Collection of Papers Written by GPs, Researchers, Specialists and Sufferers about Endometriosis. Compiled by the Coventry Branch of the Endometriosis Society, March 1987
13. Fanton JW and Golden JG. "Radiation-induced endometriosis in Macaca mulatta." Radiation Research 126: 141-46, 1991
14. Fanton JW, Hubbard GB, Wood DH. "Endometriosis: Clinical and pathological findings in 70 rhesus monkeys." American Journal of Veterinary Research 47: 1537-1541, 1986
15. Campbell JS, Wong J, Tryphonas L, et al. "Is Simian Endometriosis an Effect of Immunotoxicity?" Presented at the Ontario Association of Pathologists Forty-Eighth Annual Meeting, October 1985, London, Ontario
16. Campbell J. "Is Reproductive Wastage and Failure Related to Environmental Pollution? - Considerations of human data and findings from a rhesus model." Symposium, Ottawa: "Toxicological Pathology - Quo Vadis?" September 1988
17. Rier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. "Endometriosis in Rhesus Monkeys (Macaca mulatta) Following Chronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin." Fundamental and Applied Toxicology 21: 433-441, 1993
18. Rier SE, Spangelo BL, Martin DC, Bowman RE, Becker JL. "Tumor necrosis factor alpha and interleukin-6 production by peripheral blood mononuclear cells from rhesus monkeys with endometriosis." Journal of Immunology 150:49A, 1993
19. "Effects of estrogen, progesterone, and methoxychlor on surgically induced endometriosis in rats." Fundamental and Applied Toxicology 27:287-290, 1995
20. Cummings AM, Metcalf JL, and Birnbaum L. "Promotion of Endometriosis by 2,3,7,8-Tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison." Toxicology and Applied Pharmacology 138:131-139, 1996
21. Johnson KL, Cummings AM, Birnbaum LS. "Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls." Environmental Health Perspectives 105(7):750-755, July 1997
22. Mayani A, Barel S, Soback S, et al. "Dioxin concentrations in women with endometriosis." Human Reproduction 12(3):373-375, 1997
23. Cummings AM, Metcalf JL. "Induction of endometriosis in mice: a new model sensitive to estrogen." Reproductive Toxicology 9(3):233-238, 1995
24. Koninckx PR, Braet P, Kennedy SH, et al. "Dioxin pollution and endometriosis in Belgium." Human Reproduction 9(6):1001-1002, 1994
25. Rier SE, Martin DC, Bowman RE, et al. "Immunoresponsiveness in endometriosis: implications of estrogenic toxicants." Environmental Health Perspectives 103(supp. 7):151-156, October 1995
26. Swain Wayland R. "Human health consequences of consumption of fish contaminated with organochlorine compounds." Aquatic Toxicology 11: 357-377, 1988