Dioxin may also play an important role in the disease.  Evidence of dioxin as a catalyst for Endometriosis has been well-documented.  In a 1996 Environmental Protection Agency study, dioxin exposure was linked with increased risks for Endometriosis, as well as the increased risks of pelvic inflammatory disease, reduction of fertility, and interference with normal fetal and childhood development. The EPA conclusions regarding dioxin exposure are particularly alarming in light of a 1989 Food and Drug Administration report, which stated that "possible exposures from all other medical device sources would be dwarfed by the potential tampon exposure." Dr. Philip Tierno, Jr., Director of Clinical Microbiology and Diagnostic Immunology at the New York University Medical Center states that "dioxins, though they exist in the environment, have a worse effect when they contact mucous surfaces like the vagina."

The Endometriosis Research Center testified before the California State Senate at the invitation of Assemblyman Dennis Cardoza in 2001 in support of AB 2820, a consequential bill that will help determine the extent to which the presence of dioxin and other additives in feminine hygiene products pose risks to both women who use the products as well as their children.  Today, our organization continues to lobby for additional research into this area.

"Anatomic Abnormalities" are also considered a possible precursor to Endometriosis. In one study, researchers concluded that the depth and volume of the cul-de-sac ("Pouch of Douglas") differs in patients with Endometriosis with or without deep lesions as compared to women with a healthy pelvis (or with diseases other than Endometriosis).  In the outcome of the study,⁽¹⁰⁾ authors noted: "reduced Douglas pouch depth and volume in women with deep Endometriosis suggests that such lesions develop not in the rectovaginal septum but intraperitoneally and that burial by anterior rectal wall adhesions creates a false bottom, giving an erroneous impression of extraperitoneal origin."

Still others believe that liver disorders hold the key in predisposing a woman to the disease.  The liver regulates and removes estrogen from the body through a series of processes; if, for whatever reason, the liver begins failing to remove the estrogen, symptoms such as chronic fatigue and allergies (common in Endometriosis) can appear.  In a further conundrum, studies have also shown that the liver is a major target for TCDD [dioxin] and is severely affected by the chemical; a significant amount of persons exposed to dioxin have enlarged liver and impairment of liver functions.⁽¹¹⁾

Finally, many experts like Dr. Robert Albee, Medical Director of the Center for Endometriosis Care,⁽¹²⁾ believe that Endometriosis may in fact actually be "a combination of several factors."

Endometriosis knows no racial or socio-economic barriers, and can affect women ranging from adolescence to post-menopause.  The disease can be so painful as to render a woman unable to care for herself or her family or attend work, school or social functions.  Endometriosis affects every aspect of a woman's life, from her self-esteem to her relationships to her ability to be a contributing member of society.

Making Progress 
Research & Developments Underway
Endometriosis continues to remain significantly under-treated and under-funded.  In fiscal year 2000, the National Institutes of Health planned to spend $16.5 billion on research.  Of that funding, only $2.7 million was earmarked for researching Endometriosis.  That amounts to approximately 40 cents per patient, in stark contrast to other illnesses like Alzheimer's Disease and Lupus, which received approximately $105 and $30 per patient, respectively.⁽¹³⁾

Even in this day and age of medical advances, Endometriosis can still only be diagnosed through invasive surgery.  The average delay in diagnosis is a staggering 9 or more years,⁽¹⁴⁾ and a patient may seek the counsel of 5 or more physicians before her pain is diagnosed and addressed.  Sadder still, there is no absolute cure for Endometriosis.

American businesses lose millions of dollars each year in lost productivity and work time because of Endometriosis pain.  The cost of surgery required to diagnose the disease in each patient alone adds greatly to the financial burden of both consumers and companies alike.  The current method of diagnosis is an invasive procedure, has significant morbidity and cannot be carried out frequently to monitor efficacy of therapy and the possibility of recurrence.  

However, we are making progress.  Groundbreaking research is underway in the area of non-invasive diagnosis, with researchers at the Garden State Cancer Center in New Jersey investigating the use of radioimmunotargeting technology.  This technique holds enormous potential for the much-needed, specific, non-invasive detection and eventual treatment of Endometriosis.  The Endometriosis Research Center has joined the Cancer Center in lobbying the NIH in support of funding for this crucial research.⁽¹⁵⁾

Policymakers are also taking note of Endometriosis and the impact the disease has on our society.  The ERC continues to work with local and federal lawmakers on the authoring and passage of various Endometriosis legislation.  Our most exciting success was in October of 2002, when for the first time, Congress passed a National Resolution which "strongly supports the ERC's efforts to raise public awareness of Endometriosis throughout the medical and lay communities; and recognizes the need for better support of patients with Endometriosis, the need for physicians to better understand the disease, the need for more effective treatments, and ultimately, the need for a cure."  California, Michigan and Pennsylvania have all passed similar Resolutions; others are in the works.

Researchers have also come a long way in understanding of the biology of pain.  We know reasons for chronic or acute pain in Endometriosis patients on a cellular level include the release of such inflammatory agents at the implant site(s) as prostaglandins, bradykinin, norepinephrine and adenosine, all inflammatory mediators of hyperalgesia. It has also been shown in studies that "message centers" at the site of inflammation, called "nociceptors," have a lower threshold for pain.  By understanding how and why pain occurs, healthcare providers can offer more effective management strategies of the painful symptoms associated with Endometriosis to their patients.  In addition, many patients today are incorporating alternative therapies and pain management programs into their lives to combat their chronic symptoms. 

Today, physicians are offering their patients better recognition and eradication of the disease.  Gone are the days when "powder-burn" lesions were considered the only form of Endometriosis, present only on the reproductive organs.  Today we know that the disease comes in colors ranging from red to clear and that it can present itself nearly anywhere in the body.   We now know all forms of the disease hurt, and any stage can cause infertility.  More treatment centers are cropping up all over the United States and the world, with practices dedicated solely to the treatment of Endometriosis patients.  Surgeons know now that Endometriosis can actually be present inside adhesions (which are painful in and of themselves), and the medical community is realizing that the most effective treatment for the disease is to thoroughly remove it through excision.  Using expert techniques, adhesion prevention, Patient Assisted Laparoscopies (PAL) and many other advances in surgery, Endometriosis patients can expect better - and more effective - surgical care in the years to come.

More effective therapies are also being developed and offered to patients.  Thirty years ago, Danazol was considered the drug of choice to "cure" Endometriosis. While still prescribed by some, Danazol is no longer the first medical therapy offered to patients, nor is it touted as a "cure."  Today, GnRH agonists like Lupron, Synarel and  Zoladex are widely prescribed in an attempt to treat the disease.

What's on the horizon in medical therapy?  Many options, including GnRH antagonists.  Antagonists differ from currently available agonists in that they are designed to be more effective and offer relief without many of the side effects present in today's GnRH drugs.

Aromatase Inhibitors are also new to Endometriosis, but not gynecology.  Aromatase Inhibitors have been used in the treatment of more than 30,000 cases of breast cancer over the past 20 years.  It has been suggested in some studies that Aromatase Inhibitors offer anti-estrogenic effects with therapeutic value.

Designer estrogens like SERMs (Selective Estrogen Receptor Modulators) are being investigated in Endometriosis therapy, because they mimic the action of estrogen where it's wanted (such as in the cardiovascular and skeletal systems) but avoid estrogenic action where it's not (i.e. breast and uterine tissue).  SERMs have been shown in animal studies to prevent bone loss and estrogenic proliferation; in one such study on rhesus monkeys with Endometriosis, treatment with SERMs resulted in decreased uterine size and significant decreases in lesion size.

Alternately, Selective Progesterone Receptor Modulators (SPRMs) are also being developed. These compounds have a high degree of specificity for the progesterone receptor and act through an entirely different mechanism than existing therapies.  The developers expect SPRMs to reduce endometrial lesions with no negative effects on bone density, and are designing SPRMs for long-term use.

Use of Extracellular Matrix Modulators is also being researched.  The proliferative endometrium expresses specific enzymes; isolating and destroying these enzymes through the use of anti-estrogenics like EMMs may be the future in medical therapy of Endometriosis.

Terbutaline is currently used to prevent premature labor, but studies are underway to determine the efficacy of this drug as a potential treatment for Endometriosis pain.

RU-486 (Mifepristone), the controversial "abortion pill," may also offer women with Endometriosis some hope. In "A Preliminary Report on the Treatment of Endometriosis with Low-dose Mifepristone," published in the June 1998 American Journal of Obstetrics & Gynecology (178(6):1151-6 (ISSN: 0002-9378), investigators Kettel, Murphy, Morales and Yen presented preliminary findings on the treatment of Endometriosis with low-dose Mifepristone.  Authors concluded that "Mifepristone...resulted in symptomatic improvement."  In addition to its anti-progestin and anti-glucocoritcoid properties, RU-486 is a non-competitive anti-estrogen. As such, RU-486 blocks the capacity of the endometrial tissue to grow in response to estrogen, making Mifepristone a possible hormonal treatment for Endometriosis.  

Angiogenesis is also an extremely important area of research.  Professor Stephen Smith,⁽¹⁶⁾ well renowned for his extensive research in this exciting area, has indicated this may be a promising new treatment, though cautions us that we are still 5-10 years out from using it as a formal alternative.  Endometriosis is known to be a hormone-dependent disease.  Angiogenesis holds that ectopic tissue requires blood supply, regardless of size, location or theory of implantation. Without blood vessel development, hormone impact can be negated. Hence, cutting off their blood supply can potentially destroy Endometriosis lesions.

Angiogenesis has interesting implications on the prevention of adhesion formation as well. It may be shown through further studies that this highly complex and unique technique holds real opportunity for treatment in Endometriosis, whether alone or as an adjunct therapy.

Researchers have made great strides in the realm of Immunotherapy as well.  ERC Advisor Deborah Metzger, MD, Ph.D.,⁽¹⁷⁾ regularly incorporates this treatment, which she calls the "4 Pillars of Healing," into her patient practice everyday.  Previously overlooked but now proving to be a big part of the Endometriosis picture, immune dysfunction plagues many patients.  By treating this dysfunction, Dr. Metzger is able to treat symptoms ranging from fatigue to allergies to opportunistic infections in her patients with Endometriosis.

The role of cytokines in the pathogenesis of Endometriosis is well known, and is being further investigated as we continue our research into immunopathology. By developing a better understanding of peritoneal fluid cytokines such IL-1, IL-6, IL-8, IL-12, IL-13 and TNFa-, we may be able to develop accurate markers in predicting Endometriosis nonsurgically.(18)

"Alternative" therapies are also being widely incorporated into the regimen of treatment for many women. Once considered the "alternative," diet/nutrition, exercise, herbal remedies and complementary therapies are becoming either adjunct or preferred modalities for pain relief and treatment by many Endometriosis patients.  Widely accepted and encouraged in the medical community, these non-invasive techniques are helping many women cope with pain, decrease their symptoms and improve their overall general health.  We have come a long way from the days when such approaches were considered "fringe" and "alternative."   The ERC is currently conducting a product focus study on a new, all natural pain reliever for menstrual cramps, called Menastil®.  For more information or to join the study, please contact us.

Various other products are in development, including new forms of existing drugs (such as inhaleable lueprolide).

These new products, research developments and advances in general awareness about Endometriosis hold great promise.  While we must continue to be ever vigilant in our efforts at raising awareness about Endometriosis and more importantly, educating women and doctors alike as to the best options to manage the disease, we can be encouraged in knowing that we are on the road to unlocking the mysteries of Endometriosis.

As we continue our journey into the millennium, we must be hopeful in the knowledge that someday soon, our daughters will not suffer as we have.

REFERENCES:
1, 3, 13 - Forbes Magazine, "The Danger Within" by Alexandra Alger-12/13/99.
2 - William Fleming, Ph.D. & Chairman, A-Fem Medical Corporation.
4 -  "Breast Cancer Basics," National Alliance of Breast Cancer Organizations. http://www.nabco.org/index.php/39.
5 - "Survey Links Endometriosis To Some Cancers" by Delthia Ricks, Newsday April 1999.
6 - "Coping with Endometriosis," Weinstein, Kate.  Addison Wesley ISBN 0-201-19810-x.