Articles

Endometriosis

Introduction

Endometriosis is the presence of functioning, proliferating endometrial tissue outside the uterine cavity. It may occur anywhere in the body, but is most commonly limited to the pelvic structures. (1) Often, these implants of endometrial tissue are seen on the outside of the ovaries, the fallopian tubes, or the uterus. The exact etiology of endometriosis is unknown, but it occurs almost exclusively in menstruating women. It is rarely seen in prepubertal women, postmenopausal women, or women with amenorrhea. One theory explaining these mislocated cells is the transport theory. The transport theory suggests that viable endometrial tissue is delivered and implanted in the abdomen and other areas of the body by retrograde menstruation through the Fallopian tubes or by hematogenous or lymphatic spread. (2)

These implants respond to ovarian hormones similar to normal endometrial tissue, as both have estrogen, progesterone, and androgen receptors. They imitate the menstrual cycle and often lead to an inflammatory response in surrounding tissues. Repetitive cycles of bleeding and inflammation lead to the development of scar tissue and adhesions between adjacent peritoneal tissues. On laparoscopy, the areas of involvement might appear as multiple hemorrhagic foci composed of endometrial epithelium, stroma, and glands. (3) Ovarian endometriosis usually involves the formation of endometriomas, blood filled cysts (“chocolate cysts") ranging in size from microscopic to 10cm in size. Nodules may form on uterosacral ligaments. Fibrosis is usually present with the endometrial implants, and extensive adhesions may form between pelvic structures. (4) Women with endometriosis may experience an increased risk to other diseases such as chronic fatigue syndrome, fibromyalgia, and hypothyroidism among other disorders. (5) The fertility rate is reduced in affected women. (6)

It is difficult to estimate the true incidence of endometriosis because the disease can exist without significant symptoms, and current diagnosis requires visual affirmation of lesions during surgery. The best estimate of prevalence of endometriosis in women 15 to 44 years of age in the general population is 10 to 20 percent. (7)

Laparoscopy allows staging of the disease, which aids in selecting the appropriate method of treatment. Staging endometriosis is currently done at the time of surgery, according to the Revised American Fertility Society Classification of Endometriosis. The stages are minimal (Stage I), mild (Stage II), moderate (Stage III), and severe (Stage IV). Staging is determined by an accumulated point total. Points are assigned based on the location of the endometrial lesions, the size of the lesions, the presence of adhesions, the extent of the adhesions, and the degree of obliteration of the posterior cul-de-sac. (8)

Statistic

Endometriosis Research Center, 2002.

  • An estimated 77 million people worldwide have endometriosis.

National Institute of Child Health & Human Development, 2002.

    At least 5.5 million women in North America alone have endometriosis. About 30 percent to 40 percent of women with endometriosis are infertile, making it one of the top three causes for female infertility. Current estimates place the number of women with endometriosis between 2 percent and 10 percent of women of reproductive age. But, it’s important to note that these are only estimates, and that such statistics can vary widely.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

A patient may have endometriosis without the presence of any symptoms. The severity of the disease can vary tremendously within the asymptomatic patient and is not at all dependent on the severity of symptoms. General symptoms for endometriosis may include but is not limited to dysmenorrhea, dyspareunia, infertility, pelvic pain, pain with defecation, abnormal uterine bleeding. During an exam, characteristic physical findings may include multiple tender nodules palpable along the uterosacral ligament at the time of vaginal-rectal examination, posteriorly fixed uterus and possibly enlarged cystic ovaries.

Other organ systems can be affected by endometrial tissue. This would allow endometriosis to present with a variety of other symptoms depending on the organ affected. If the intestines are involved painful defecation may occur or rectal bleeding may be present. When the bladder or ureters are involved an individual may experience hematuria, dysuria or possibly cyclic flank pain. On rare occasions, hemoptysis that occurs during menstruation may be present if endometrial lesions are located in the pleura. (9)

General

    Dysmenorrhea Dyspareunia Infertility Pelvic pain Pain with defecation Abnormal uterine bleeding

Treatment Options

Conventional

Treatment depends upon the degree of involvement and the desires of the patient. It includes observation for mild disease with no associated infertility or pain, hormonal suppressive therapy, conservative surgery if fertility is desired, or removal of the uterus, tubes, and ovaries in severe disease. (10)

Hormonal therapy involves the use of estrogen-progestin combinations (birth control pills) to induce a state of pseudopregnancy. When given in a chronic, continuous administration a state of hyperhormonal amenorrhea results. The combination products used contain a progestational agent such as norethynodrel, norethindrone, and norgestrel, in combination with either ethinyl estradiol or mestranol, and are generally administered on a continuous basis for six to nine months.

Another option of hormonal therapy is progestin therapy alone. Medroxyprogesterone may be administered either orally or intramuscularly to induce anovulation. The most frequently used dose is 10mg orally three times daily for three months. Usually, pelvic pain and tenderness begin to disappear within a few days of starting therapy. Alternatively, medroxyprogesterone acetate injection can be given intramuscularly in doses of 100mg every two weeks for eight weeks, followed by 200mg every month for four months. (11)

A pseudomenopausal condition can also be induced by the administration of danacrine, a synthetic derivative of 17-a-ethinyl testosterone. This suppresses the release of LH and FSH from the pituitary and is generally given in doses of 400 to 800mg/day for a period of six to nine months.

The GnRH agonist nafarelin has been approved by the FDA for pelvic pain and implant shrinkage in endometriosis. The recommended dose is 200mcg every 12 hours administered intranasally. It works to prevent the pulsed release of endogenous GnRH from the hypothalamus.

Each of these therapies has been proven effective, but should be carefully reviewed for side effect profile, adverse events, relative cost of therapy, and potential for relapse after treatment is stopped.

Nutritional Supplementation

This category contains no therapies clinically applicable to this disease state.

Herbal Supplementation


Chasteberry

The chasteberry tree finds its origins in the Mediterranean. Its fruit is harvested and dried for medicinal purposes. It has a long folk history of use in women’s health. Chasteberry has been recommended for use in mild to moderate complaints, especially in endometriosis, menopause, and PMS symptoms. The actual activity of the constituents of chasteberry is not fully established at this time. Studies have reported it to have significant effect on the pituitary. (12) , (13) Studies point to a progesterone-like component and effect. (14) , (15) Studies report that vitex stimulates luteinizing hormone (LH) and inhibits follicle stimulating hormone (FSH). (16) , (17) Because of this activity, vitex has been recommended for a variety of female complaints, such as PMS, amenorrhea, menopausal symptoms, endometriosis, and hyperprolactinemia. (18) , (19) , (20) Several studies have reported beneficial effects of vitex on female-related disorders. (21) , (22) Several clinical studies have reported beneficial results with using chasteberry in treating women with infertility associated with corpus luteum deficiency. (23)


Evening Primrose

Evening primrose oil (EPO) is rich in gamma-linolenic acid which is an omega-6 fatty acid. (24) , (25) Omega-6 fatty acids reportedly reduce the arachidonic acid cascade and decrease inflammation through inhibiting the formation of inflammatory mediators in this process. Supplementation with essential fatty acids such as EPO has been shown to prevent zinc deficiency, thereby potentially improving immunity. (26) Fatty acids are an important part of normal homeostasis. The human body can produce all but two fatty acids - omega-3 and omega-6 fatty acids. Both must be obtained through the diet or by the use of supplements. Obtaining a balance of these two fatty acids is essential. Essential fatty acids are needed for building cell membranes and are precursors for production of hormones and prostaglandins. Modern diets tend to be lacking in quality sources of fatty acids.


Red Clover

Red clover has been used traditionally as a medicinal agent by Oriental, European, and Native American cultures as an expectorant, in asthma, and as an alterative (blood purifier) to treat psoriasis, eczema, and other chronic skin conditions. (27) There has been a great deal of research and reviews on the effects of phytoestrogens (or plants that contain chemical entities that have estrogenic activities in the body) as they relate to menopausal symptoms. (28)

Recently, a proprietary extract of red clover, standardized to the phytoestrogen content, has gained a great deal of attention in the management of menopause and related symptoms. Research has focused on the red clover extract which contains four principle phytoestrogens (biochanin A, fomonontein, genistein, and daidzein), all with reported levels of estrogen-like activity. (29) Red clover is reported to have the following effects:

    Estrogenicity- interaction with human estrogen receptor sites. (30) Their estrogenic effect relative to 17b-estradiol is between 1-5 x 10-3. (31) Steroidogenesis- isoflavones modulate a range of enzymes that regulate the production, metabolism, and function of steroidal hormones, including: inhibiting 17b-hydroxysteroid dehydrogenase which is involved in the synthesis of 17b-estradiol; (32) inhibiting aromatase which converts androstenedione to estrone; (33) and inhibiting 5-a-reductase which converts testosterone to dihydrotestosterone. (34) Other activities include inhibition of the oxidation of steroid hormones (35) and the promotion of the production of sex-hormone binding globulin (SHBG) by liver cells. (36) Cell growth and differentiation- Genistein is an inhibitor of a range of enzymes that modulate cell transduction processes involved in cell growth and differentiation; the principal enzymes are protein tyrosine kinases, and DNA topoisomerases. (37) , (38) , (39) Genistein blocks the growth of normal human lymphocytes and human leukemic cells by arresting growth in the G2/M phase of the cell cycle. (40) Genistein induces terminal differentiation and inhibits proliferation of human and rodent leukemic and melanoma cells and it also induces apoptosis of mouse leukemic cells in vivo. (41) , (42)


Olive Leaf

Olive leaf extract has been reported to be an effective antimicrobial agent against a wide variety of pathogens, including Salmonella typhi, Vibrio parahaemolyticus and Staphylococcus aureus (including penicillin-resistant strains), Klebsiella pneumonia and Eschericha coli, causal agents of intestinal or respiratory tract infections in man. (43) The component usually associated with olive leaf’s antimicrobial properties is oleuropein. (44) , (45) Oleuropein also has been reported to directly stimulate macrophage activation in laboratory studies. (46)

Olive leaf extract has reported antiviral activity, reportedly caused by the constituent calcium elenolate, a derivative of elenolic acid. (47) , (48) As an antifungal and antiviral agent, olive leaf extract is currently used as a supportive agent in maintaining bowel flora, essential in decreasing candidal overgrowth (a causative agent in female-related disorders). Recent studies in laboratory animals reported hypoglycemic and hypolipidemic activity. (49) , (50) The constituent with the activity was reported to be oleuropein, with a proposed mechanism of action being: (1) potentiation of glucose-induced insulin release, and (2) an increase in peripheral blood glucose uptake.


Cat's Claw

Cat’s claw reportedly affects the immune system and acts as a potent free radical scavenger. (51) Cat’s claw has glycosides which reportedly reduce inflammation and edema. (52) The anti-inflammatory effects of cat’s claw are considered to be due to the sum total of the plant’s constituents, but the sterols have demonstrated anti-inflammatory activity in animal studies. The glycosides are also reported to enhance and stimulate phagocytosis, which if true would be a key part of cat’s claw’s immune function activity. (53) Isopteridine, an alkaloid which has been isolated, is claimed to have immuno-stimulatory properties. Triterpenoid alkaloids and quinovic acid glycosides have been isolated and studied for antiviral activity, possibly inhibiting replications of some DNA viruses. (54) , (55)

Cat’s claw is reported to have the ability to soothe irritated and inflamed tissues and help eliminate pathogens from the GI tract. (56)

Homeopathic

Apis mellifica

Typical Dosage: 6X or 6C, 30X or 30CBurning; Stinging pains; Ovaritis (predominately right-sided)

Belladonna

Typical Dosage: 6X or 6C, 30X or 30CAbdomen swollen and sensitive to touch; Stitching pain

Kali iodatum

Typical Dosage: 6X or 6C, 30X or 30CPressure in the uterus when walking; Griping pain in abdomen

Lachesis mutus

Typical Dosage: 6CLeft-sided ovarian pain; Cannot bear pressure

Acupuncture & Acupressure

Acupuncture-Moxibustion Therapy

Ni et al. treated 54 cases of pain associated with endometriosis with acupuncture and moxibustion. The treatment consisted three parts: 1) body acupuncture: acupuncture was applied on Zhong Ji (CV 3), Guan Yuan (CV 4), Qi Hai (CV 6), and San Yin Jiao (SP 6), with the needles maneuvered by the uniform reinforcing-reducing method and retained for 20 minutes; 2) auriculo-acupuncture: one or two days prior to the onset of the menstrual period, auricular needles were embedded at otopoints related to the ovary, sympathetic nerves, and endocrine (alternatively, otopoint sticking therapy with vaccaria seeds could be used in lieu of needle embedment); and 3) moxibustion: moxibustion with moxa sticks was performed for 10-15 minutes at any one or two of the following points: Yin Bai (SP1), Yin Ling Quan (SP9), and Di Ji (SP8). Moxibustion was performed only on the patients treated with body acupuncture for lower abdominal pain. One course of treatment consisted of two sessions of body acupuncture and one session of auriculo-acupuncture. The results: after 1-3 courses of treatment, 4 cases were resolved, 29 cases were greatly improved, another 1 case improved slightly, and the remaining 4 cases did not respond to the treatment, with the total effectiveness rate of 92.6%. (57)

Traditional Chinese Medicine

Endometriosis

Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Additional Hormone Assessment

Insulin: Some medication used in the treatment of endometriosis may increase insulin resistance. (58) Monitoring insulin levels for hypersecretion may be useful in preventing iatrogenic disorder.

Estrogen: Endometriosis is an estrogen-responsive disorder. Monitoring may be useful. (59)

Prolactin: Elevations occurring in endometriosis are associated with infertility. (60) Prolactin and estrogen supplementation may reduce pain. (61)

Clinical Notes

Natural Progesterone: The symptoms of endometriosis frequently undergo a substantial decline during pregnancy, which is a time when a woman’s body produces elevated levels of progesterone. This observation led many physicians to treat this condition with progestogens. (62) Unfortunately, progestogens can cause a substantial number of well-known side effects, which frequently result in a disruption and/or discontinuation of therapy. However, noted physician/author Dr. John Lee has reported successfully treating a number of women with endometriosis, some after unsuccessful surgeries, with natural progesterone. (63) ACCORDING TO HIS SUGGESTION: women should topically apply natural progesterone cream from day 6 of their cycle to day 26 each month. One ounce of cream is used per week for three weeks, stopping just before their expected period. Reports suggest that the results of this protocol usually takes from four to six months. Although patience is required, there is generally a gradual improvement in symptoms as the inflammation begins to subside and the tissues begin to heal. Some women may not recover completely, but the condition usually becomes much more tolerable.

Vitamin E: It has been suggested that endometriosis generates a high level of oxidative stress. One study reported that activated macrophages in the peritoneal cavity generate an oxidative stress, which consists of lipid peroxides, their degradation products, and products formed from their interaction with low-density lipoprotein (LDL), apoprotein and other proteins. The lipoproteins of the peritoneal fluid (interstitial fluid) have been shown to have lower vitamin E levels and to be more readily oxidized than plasma, so peritoneal fluid may actually contribute to the disease process actively rather than as a passive carrier of mediators of inflammation and growth. This information suggests that supplemental doses of vitamin E might be helpful in reducing some of the pain, inflammation, and disease process associated with endometriosis. (64) Of course, additional antioxidant nutrients might work synergistically with vitamin E.

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