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Endometriosis: The Four Pillars of Healing

Endometriosis: The Four Pillars of Healing

by Deborah A. Metzger, MD, PhD, USA, Endozone Advisory Board member, Medical Director, Helena Women's Health

Treatment options for women with endometriosis are quite limited and generally directed at eradicating or suppressing the implants. Recurrence of symptoms following treatment if common, implying that these treatments fail to address the systemic manifestations of the disease. One of the challenges to health care providers is to provide patients with optimal management of the common symptoms of endometriosis: pelvic pain, dysmenorrhea, and fatigue.  Over the past 11 years, my practice has consisted predominantly of caring for women with endometriosis, particularly those who have not had success with the standard treatments for endometriosis. As a result of their suggestions and willingness to try new approaches, I have developed an approach that I call the 'Four Pillars of Healing' (7). The following four approaches form the foundation for the science and art of the treatment of endometriosis: 1) accurate diagnosis, 2) thorough excision of implants, 3) hormonal therapy, and 4) immunotherapy.

Accurate Diagnosis
The most common tool for the diagnosis of chronic pelvic pain is a diagnostic laparoscopy under the assumption that whatever is causing the pain will be visible. Endometriosis implants are usually visible, but other, more subtle appearances of the disease can be missed, particularly in young women. Once the diagnosis of endometriosis is made, all of the patient's pain symptoms
are often attributed to endometriosis, even though other sources of pain are commonly found in association with endometriosis such as interstitial cystitis, occult inguinal hernias (15), abdominal wall trigger points, vulvodynia, ovarian vein syndrome (17), ovarian remnant syndrome and pelvic floor tension myalgia (14). Screening for these sources of pain should be a routine part of the assessment of any woman with chronic pelvic pain (16). Optimal resolution of pelvic pain will depend on treatment directed toward all of the causes of chronic pelvic pain.

Thorough Excision of Implants
For superficial implants, ablation of the implants is sufficient. However, for implants that demonstrate scarring, retraction, immobility of the peritoneum, or nodularity, wide local excision is necessary to remove the entire implant. Failure to excise deep-seated implants in the cul-de-sac, particularly where there is complete or partial obliteration of the cul-de-sac, may be responsible for rapid recurrence of symptoms following surgery or hormonal suppression.  Bowel resection may be necessary in some cases. Endometriomas respond poorly to hormonal suppression and recurrence is common following surgical drainage. The endometrioma capsule must be removed in order to minimize recurrence. Selected patients may benefit from adjunctive pain relieving measures such as presacral neurectomy, uterosacral nerve transection or uterine suspension (13).

Although effective in relieving pain, surgery removes the implants but leaves the systemic disease intact, which may explain the recurrence of symptoms in 12-54% of all women within a year of surgery (3). Thus, surgery should not be viewed as curative, but merely a way of debulking disease to improve response to the other three pillars of treatment.

Hormonal Therapy
Given the clear association between oestrogen exposure development and progression of endometriosis, medical therapy for patients with endometriosis is most frequently based on the need to produce a hypoestrogenic environment that can be achieved using gonadotropin releasing hormone analogues, high dose progestins, danocrine or continuous oral contraceptives. Controlled
studies show a high degree of efficacy of hormonal therapy when relief of pain and dysmenorrhea are used as endpoints. However, dysmenorrhea invariably returns with the resumption of cyclic menses and approximately 25-30% report recurrence of pelvic pain symptoms within 6 months of treatment (4, 6, 21).

Women who are more likely to have recurrences include those with severe disease, deep fibrotic disease or large endometriomas which are better managed surgically. Continuous oral contraceptives (OCP's) may be used to continue the hormonal suppression and symptom improvement initially achieved with GnRH agonists or other hormonal therapy. Unlike surgical treatment, hormonal therapy appears to have beneficial effects on the immune system (5).

In spite of the overwhelming evidence suggesting an immune imbalance in women with endometriosis, little attention has been paid to treating the immune system. In treating women with endometriosis. I have been impressed by the large proportion of these women who continue to complain of fatigue in spite of relief of their pain, implying that the systemic part of the disease has not been addressed. Because fatigue can result from a variety of conditions, I routinely perform a fatigue screening workshop that includes the following tests: Zung depression questionnaire, complete blood count with differential, sedimentation rate, liver functions, antinuclear antibody, free T4, TSH, magnesium, calcium, creatinine, BUN, Lyme screen with confirmatory western blot, AM/PM cortisol, glycosylated hemoglobin, rheumatoid factor, and HIV. In a series of 40 consecutive endometriosis patients with fatigue, but no pain, 11 patients had mild to moderate depression while on antidepressant therapy, one patient was found to have adrenal insufficiency, 4 had mild hypothyroidism, 4 had mild anaemia and 2 had Lyme disease (18). Almost without exception, fatigue persisted in spite of correction of these abnormalities.

An often overlooked cause of fatigue is allergy to environmental (pollen, dust mites, molds, cold, heat) or endogenous (foods, drugs, Candida, hormones) allergens. Any of these substances can trigger an immediate or delayed hypersensitivity reaction that is manifested as nasal congestion, asthma, diarrhoea / constipation, skin rashes, fever, fatigue, muscle pain, and/or joint pain. Often the responsible allergen(s) is something that a persons comes in contact with on a regular basis. In the previously described series of 40 patients with fatigue, 67.5% (27) had allergic symptoms and were positive for IgE and/or IgG mediated allergies (18). Identification of and desensitisation to the offending allergen(s) has alleviated fatigue in about one-third of patients with endometriosis.

Increasingly there are reports of an association between endometriosis and opportunistic infections, specifically with Candida albicans (10). Half of the women in our fatigue study had an overgrowth of Candida species on stool culture (18). Moreover, a high proportion of women with endometriosis have antibodies to Candida (9). It is not known if C albicans is a primary
pathogen or an opportunist and marker for other underlying problems, or both.  C albicans is a potent antigen that induces production of interleukin-1 (1), tumor necrosis fact (2) and interleukin-6 (8). It activates macrophages (20) and at the same time can inhibit phagocytosis (19). Women with recurrent Candidal vaginitis have perupheral monocytes that are defective in their ability to proliferate in response to Candidal antigens and have elevated antibody titers to C. albicans in their serum and vaginal washings. Although there is an extensive European literature regarding the association between endometriosis and Candida, the lack of published research in western peer reviewed journals has inhibited pursuit of this association (11). My patients have reported that treatment of Candida is as important as surgery and hormonal therapy in contributing to their return to health (12).

Desensitisation, neutralization and tolerization are treatments commonly used to treat allergic symptoms that are not responsive to medications.  Three-year follow-up of oral tolerization with dilute solutions of Candida has been proven beneficial in women with Candida allergies (9). Moreover, Kresch (9) has also shown that 87% of women with endometriosis have allergies to estradiol, progesterone or LH compared to 22% of control women. The results of neutralization treatment during a three-year follow-up reveals significant improvement in symptoms in the majority of patients.

Other non-specific treatments directed toward decreasing stress and improving immune function have also been utilized with success in the overall management of fatigue associated with endometriosis. A low refined carbohydrate diet consisting of no caffeine, no sugar and no preservatives/additives has been helpful along with the addition of a multivitamin with minerals. Physical activity, such as walking or swimming, has been helpful in reducing pain. Attention to reduction of emotional stress through meditation, counselling, antidepressants, and stress management can contribute greatly to the overall success of an endometriosis program.

The rationale behind the treatment of endometriosis is based on the factors thought to be involved in its pathogenesis: retrograde menstruation, implants, oestrogen and the immune system.  One of the reasons that recurrence of symptoms is common among women with endometriosis may be that only one or two of the pillars of healing has been utilized.  We may be able to achieve more long-term successes by routinely employing all four of the pillars of healing for endometriosis.

(1) Ausiello CM, Urbani F. Gessani, et al (1993). Cytokine gene expression in human peripheral blood monomuclear cells stimulated by mannoprotein constituents from C. albicans. Infect Immun 61:4105-4111.

(2)  Blasi E, Pitzurra L, Pulita M, et al (1992). C. albicans hyphal form enhances tumor necrosis factor mRNA levels and protein secretion in murine ANA-1 macrophages. Cell Immunol 142:137-144.

(3)  Candiani GB, Fedele L, Vercellini P, Bianchi S, DiNola G. Repetitive conservative surgery for recurrence of endometriosis. Obstet Gynecol  1991; 77:421-424

(4)  Dlugi AM, Miller JD, Knittle K. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double blind study. Fertil Steril 54:419-27, 1990.

(5)  Dmowski WP, Braun DP (1997). Immunologic aspects of endometriosis. In Endometrium & Endometriosis (Diamond MP, Osteen KG, eds) Blackwell Science, Malden MA, 174-181.

(6)  Fedele L, Parazzini F, Bianchi S, et al (1990). Stage and localization of pelvic endometriosis and pain. Fertil Steril 53: 155-158.

(7)  Galland, Leo. The Four Pillars of Healing. Random House, New York, 1997.

(8)  Ghezzi MC, Raponi G, Filadoro F, et al (1994). The release of TNF-a and IL-6 from human monocytes stimulated by filtrates of C. albicans after treatment with amphotericin B. J Antomierob Chemother 33:1039-1043.

(9)  Kresch AJ. Combining new immune therapies with traditional endometriosis treatment. Presented as an abstract at the 25th Annual Meeting of the AAGL, Chicago, IL, Sept. 24-29, 1996.

(10)  Lamb K, Nichols TR (1986). Endometriosis: A comparison of associates disease histories. Am J Prev Med 2:324-329.

(11)  Mabray CR (1997). The allergy-endocrine-endometriosis connection. In, Endometrium & Endometriosis (Diamond MP, Osteen KG, eds) Blackwell Science, 342-346.

(12)  Metzger DA. Efficacy of conventional and alternative treatments for endometriosis. VI World Congress on Endometriosis, June 30 - July 4, 1998, Quebec.

(13)  Metzger DA. An integrated approach to endometriosis. In, Chronic Pelvic Pain: An Integrated Approach (Steege JA, Metzger DA, Levy B, eds) WB Saunders Co, Philadelphia, 1998.

(14)  Metzger DA. Additional sources of pain in women with treatment resistant or recurrent endometriosis. International Congress of Gynecologic Endoscopy AAGL 27th Annual Meeting, Nov. 10-15, 1998, Atlanta, GA.

(15)  Metzger DA, Daoud I. Occult hernias in women with chronic pelvic pain. International Cognress of Gynecologic Endoscopy AAGL 26th Annual Meeting, September 23-28, 1997, Seattle, WA (plenary abstract).

(16)  Metzger DA, Daoud I, Bosco P, Peters-Gee J. A systematic approach to the diagnosis and management of chronic pelvic pain. International Congress of Gynecologic Endoscopy AAGL 27th Annual Meeting, Nov. 10-15, 1998, Atlanta,
GA (plenary abstract).

(17)  Metzger DA, Epstein N. Conservative management of chronic pelvic pain associates with ovarian vein varicosities. International Congress of Synecologic Endoscopy AAGL 26th Annual Meeting, September 23-28, 1997,
Seattle, WA.

(18)  Metzger DA, Santilli J. Fatigue associates with endometriosis. VI World Congress on Endometriosis, June 30 - July 4, 1998, Quebec.

(19)  Szabo I, Guan L. Rogers TJ (1995). Modulation of macrophage phagocyctic activity by cell wall components of C. albicans. Cell Immunol 164:182-188.

(20)  Vasquez N, Buckley HR, Mosser DM, et al (1995). Activation of murine resident peritoneal macrophages by a cell wall extract of C. albicans. J Med Vet Mycol 33:385-393.

(21)  Waller KG, Shaw RW.  Conadotropin-releasing hormone analogue for endometriosis recurrence after treatment. Br J Obstet Gynaecol 100:177, 1993.