Endometriosis (from endo, "inside", and metra, "womb") is a common medical condition in women that is characterized by growth beyond or outside the uterus of tissue resembling endometrium, the tissue that normally lines the uterus.

Endometriosis is typically seen during the reproductive years; it has been estimated that it occurs in roughly 5% to 10% of women.^[1] Its main but not universal symptom is pelvic pain in various manifestations; further, endometriosis is a common finding in women with infertility.

Symptoms

Pelvic pain

A major symptom of endometriosis is severe recurring pelvic pain. The amount of pain a woman feels is not necessarily related to the extent or stage (1 through 4) of endometriosis. Some women will have little or no pain despite having extensive endometriosis affecting large areas or having endometriosis with scarring. On the other hand, women may have severe pain even though they have only a few small areas of endometriosis. Symptoms of endometriosic-related pain may include:

• dysmenorrhea - Painful, sometimes disabling menstrual cramps; pain may get worse over time (progressive pain) also lower back pains linked to the pelvis
• Chronic pelvic pain - typically accompanied by lower back pain and/or abdominal pain.
• dyspareunia - Painful sex
• dyschezia - Painful bowel movements
• dysuria - Urinary urgency, frequency, and sometimes painful voiding

Infertility

Many women with infertility have endometriosis. As endometriosis can lead to anatomical distorsions and adhesions the causality may be easy to understand, however the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited.^[2] It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility^[3] in such cases.

Other

Other symptoms may be present, including:

• Nausea, vomiting, and/or diarrhea - particularly just prior or during the period
• frequent menses flow or short menstrual cycle.
• Heavy and/or long menstrual periods.
• Some women may also suffer mood swings and fatigue.

In addition, women who are diagnosed with endometriosis may have gastrointestinal symptoms that may mimic irritable bowel syndrome.

Patients who rupture an endometriotic cyst may present with an acute abdomen as a medical emergency.

Epidemiology

Endometriosis can affect any woman, from premenarche to postmenopause, regardless of her race, ethnicity or whether or not she has had children. It is primarily a disease during the reproductive years. Estimates about its prevalence vary but 5-10% is a reasonable number, more common in women with infertility (20-50%) and women with chronic pelvic pain (about 80%).^[4] As an estrogen-dependent process it usually has run its course by the arrival of menopause.

Endometriosis in postmenopausal women is rare and has been described as an aggressive form of this disease characterized by complete progesterone resistance and extraordinarily high levels of aromatase expression.^[5] A majority of 50 postmenopausal women diagnosed with endometriosis had no previous history of the disease. In even less common cases, girls may have endometriosis before they even reach menarche.^[6][7]

Pathology and locations

Typical endometriotic lesions show a histologic feature similar as endometrium, namely stroma and endometrial epithelium and glands that respond to hormonal stimuli. Older lesions may display no glands but hemosiderin deposits as residual. To the eye, lesions appear dark blue or powder-burn black and vary in size; other lesions are red, white, or non-pigmented. Additionally other lesions may be present, notably endometriomas of the ovary, scar formation, and peritoneal defects or pockets. Some lesions may not be visible to the eye, as normal appearing peritoneum of infertile women reveals endometriosis on biopsy in 6-13% of cases.^[8]

Early endometriosis typically occurs on the surfaces of organs in the pelvic and intra-abdominal areas. Health care providers may call areas of endometriosis by different names, such as implants, lesions, or nodules. Larger lesions may be seen within the ovaries as endometriomas or chocolate cysts (they are termed chocolate because they contain a thick brownish fluid, mostly old blood). Endometriosis may trigger inflammatory responses leading to scar formation and adhesions.

Most endometriosis is found on theses structures in the pelvic cavity where it may produce intense to no pain^[9] felt in the pelvis, low back, and during premenstrual period:

• Ovaries, most common site
• Fallopian tubes
• The back of the uterus and the posterior culdesac
• The front of the uterus and the anterior culdesac
• Uterine ligaments such as the broad or round ligament of the uterus
• Pelvic and back wall
• Intestines, most commonly the rectosigmoid. Bowel endometriosis affects approximately 10% of women with endometriosis, and can cause severe pain with bowel movements.
• Urinary bladder and ureters

Endometriosis may spread to the cervix and vagina or to sites of a surgical abdominal incision.

Less commonly lesions can be found on the diaphragm. Diaphragmatic endometriosis is rare, most always on the right hemidiaphragm, and may inflict cyclic pain of the right shoulder just before and during menses. Rarely, endometriosis can be extraperitoneal and is found in the lungs and CNS.^[10]

Pleural implantations are associated with recurrent right pneumothoraces at times of menses, termed catamenial pneumothorax.

Complications

complications of endometriosis include:

• Internal scarring
• Adhesions
• Pelvic cysts
• Chocolate cysts
• Ruptured cyst

Infertility can be related to scar formation and anatomical distortions due to the endometriosis, however, endometiosis may also interfere in more subtle ways: cytokines and other chemical agents may be released that interfere with reproduction.

Complications of endometriosis consist of bowel and ureteral obstruction resulting from pelvic adhesions. Also, peritonitis from bowel perforation can occur.

Diagnosis

A health history and a physical examination can in many patients lead the physician to suspect endometriosis.

Use of imaging tests may identify larger endometriotic areas, such as nodules or endometriotic cysts. The two most common imaging tests are ultrasound and magnetic resonance imaging (MRI). Normal results on these tests do not eliminate the possibility of endometriosis--areas of endometriosis are often too small to be seen by these tests.

The only way to confirm and diagnose endometriosis is by laparoscopy or other types of surgery. The diagnosis is based on the characteristic appearance of the disease, if necessary corroborated by a biopsy. Laparoscopy also allows for surgical treatment of endometriosis.

Staging

Surgically, endometriosis can be staged I-IV (Revised Classification of the American Society of Reproductive Medicine).^[11] The process is a complex point system that assesses lesions and adhesions in the pelvic organs; in principle the various stages show these findings:

• Stage I (Minimal)

Findings restricted to only superfical lesions and possibly a few filmy adhesions.

• Stage II (Mild)

In addition, some deep lesions are present in the culd de sac.

• Stage III (Moderate)

As above, plus presence of small endometriomas on the ovary and more adhesions.

• Stage IV (Severe)

As above, plus larger endometriomas, extensive adhesions.

Markers

An area of research is the search for endometriosis markers. These markers are substances made by or in response to endometriosis that health care providers can measure in the blood or urine. If markers are found, health care providers could diagnose endometriosis by testing a woman's blood or urine which might show high levels of estrogen or low levels of progesterone, and reduce the need for surgery. CA-125 is known to be elevated in many patients with endometriosis,^[12] but not specifically indicative of endometriosis.

Potential causes

While the exact cause of endometriosis remains unknown, many theories have been presented to better understand and explain its development. These concepts do not necessarily exclude each other.

1. Estrogens: Endometriosis is a condition that is estrogen-dependent and thus seen primarily during the reproductive years. In experimental models, estrogen is necessary to induce or maintain endometriosis. Medical therapy is often aimed at lowering estrogen levels to control the disease. Additionally, the current research into aromatase, an estrogen-synthesizing enzyme produced by the implants themselves, has provided evidence as to why and how the disease persists after menopause and hysterectomy.
2. Retrograde menstruation: The theory of retrograde menstruation (first proposed by John A. Sampson) suggests that during a woman's menstrual flow, some of the endometrial debris exits the uterus through the fallopian tubes, and may attach itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. While most women may have some retrograde menstrual flow, typically their immune system is able to clear the debris and prevent implantation and growth of cells from this occurrence. However, in some patients, endometrial tissue transplanted by retrograde menstruation may be able to implant and establish itself as endometriosis. Factors that might cause the tissue to grow in some women, but not in others, need to be studied, and some of the possible causes below may provide some explanation, e.g. hereditary factors, toxins, or a compromised immune system. It can be argued that the uninterrupted occurrence of regular menstruation month after month for decades is a modern phenomenon, as in the past women had more frequent menstrual rest due to pregnancy and lactation. Sampson's theory certainly is not able to explain all instances of endometriosis, and needs additional factors (genetic and/or immune differences) to account for the fact that many women with retrograde menstruation do not have endometriosis.
3. Metaplasia: A competing theory suggests that endometriosis does not represent transplanted endometrium but starts de novo from local stem cells. This process has been referred to as coelomic metaplasia or embryologically patterned metaplasia. This theory states that cells with the potential to become endometriosis are laid down in tracts during embryologic development. These tracts are typically in the posterior pelvis, possibly forming as the female reproductive (Mullerian) tract migrates caudally at 8-10 weeks of embryonic life. These cells act like seeds or stem cells, lying dormant until puberty when ovarian estrogen production starts and stimulates their growth. Active endometriosis produces inflammatory mediators that cause pain and inflammation, as well as scarring or fibrosis of surrounding tissue Triggers of various kind (including menses, toxins, or immune factors) may be necessary to start this process.
4. Genetics: Hereditary factors play a role. It is well recognized that daughters or sisters of patients with endometriosis are at higher risk of developing endometriosis themselves, for example low progesterone levels may be genetic, and may contribute to a hormone imbalance. There is an about 10-fold increased incidence in women with an affected first-degree relative.^[4] A recent study (2005) published in the American Journal of Human Genetics found a link between endometriosis and chromosome 10q26.^[13] One study found that, in female siblings of patients with endometriosis the relative risk of endometriosis is 5.7:1 versus a control population.^[14]
5. Transplantation: It is accepted that in specific patients endometriosis can spread directly. Thus endometriosis has been found in abdominal incisional scars after surgery for endometriosis. It can also grow invasively into different tissue layers, i.e. from the culdesac into the vagina. On rare occasions endometriosis may be transplanted by blood or by the lymphatic system into peripheral organs (e.g. lungs, brain).
6. Immune system: Research is focusing on the possibility that the immune system may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to autoimmune disease, allergic reactions, and the impact of toxins.^[15] However it is still unclear what, if any, causal relationship exists between toxins, autoimmune disease, and endometriosis.
7. Environment: There's a growing sentiment that there are environmental factors which may cause endometriosis; specifically some plastics, and cooking with certain types of plastic containers with microwave ovens.http://www.ksl.com/?nid=148&sid=2223164 Other sources suggest that pesticides and hormones in our food cause a hormone imbalance.

Cause of pain

The way endometriosis causes pain is the subject of much research. Because many women with endometriosis feel pain during or related to their periods and may spill further menstrual flow into the pelvis with each menstruation, some researchers are trying to reduce menstrual events in patients with endometriosis.

Endometrial tissue reacts to hormonal stimulation and may "bleed" at the time of menstruation. It accumulates locally, causes swelling, and triggers inflammatory responses with activation of cytokines. It is thought that this process may lead to pain perception.

Women with endometriosis commonly have problems with extraordinarily painful periods and severe cramps. In severe cases, the bleeding can be profound and continue for weeks, leading some women to require iron supplements and even blood transfusions. These women are usually treated with birth control pills, hormone therapies, IUDs with hormones, drugs that induce menopause, or even hysterectomy to stop the dysmenorrheal symptoms.

While the menstrual pain itself can be quite excruciating, it is not the only time a person with endometriosis suffers. The lesions cause scar tissue to grow in the abdomen (and sometimes elsewhere), which can bind internal organs to each other, causing organ dislocation. Fallopian tubes, ovaries, the uterus, the bowels, and the bladder can be permanently damaged. When it occurs, this kind of pain can be debilitating on a daily basis. In addition to pain caused by the disease directly, surgical treatment can also be quite painful and lead to secondary pain from complications including adhesion formation. Patients with endometriosis may face laparoscopy, laparotomy, hysterectomy, oophorectomy, bowel and bladder surgeries. common.

Treatments

While there is no cure for endometriosis, in many patients menopause (natural or surgical) will abate the process. In patients in the reproductive years, endometriosis is simply managed: the goal is to provide pain relief, to restrict progression of the process, and to relieve infertility if that should be an issue. In younger women with unfulfilled reproductive potential, surgical treatment tends to be conservative, with the goal of removing endometrial tissue and preserving the ovaries without damaging normal tissue. In women who have need to maintain their reproductive potential, hysterectomy and/or removal of the ovaries may be an option; however, this will not guarantee that the endometriosis and/or the symptoms of endometriosis will not come back, and surgery may induce adhesions which can lead to complications.

In general, patients are diagnosed with endometriosis at time of surgery, at which time ablative steps can be taken. Further steps depend on circumstances: patients without infertility can be managed with hormonal medication that suppress the natural cycle and pain medication, while infertile patients may be treated expectantly after surgery, with fertility medication, or with IVF.

Sonography is a method to monitor recurrence of endometriomas during treatments.

It is suggested, but unproven, that pregnancy and childbirth can cease the growth of endometriosis.. Nevertheless, after the pregnancy, there is no guarantee that the endometriosis will not recur.

Treatments for endometriosis in women who do not wish to become pregnant include:

Medication

• NSAIDs not only reduce pain but also reduce menstrual flow. They are commonly used in conjunction with other therapy. For more severe cases narcotic prescription drugs may be used.
• Progesterone or Progestins: Progesterone counteracts estrogen and inhibits the growth of the endometrium. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.
• Avoiding products with xenoestrogens, which have a similar effect to naturally produced estrogen and can increase growth of the endometrium.
• Hormone contraception therapy: This approach uses oral contraceptives to reduce or eliminate menstrual flow and estrogen support. Typically, it is a long-term approach. Newer OCs allow to reduce the number of menstrual events by inducing a menses every 3 months or even less. Continuous hormonal contraception consists of the use of combined oral contraceptive pills without the use of placebo pills, or the use of NuvaRing or the contraceptive patch without the break week. This eliminates monthly bleeding episodes.
• Danazol (Danocrine) and gestrinone are suppressive steroids with some androgenic activity. Both agents inhibit the growth of endometriosis but their use remains limited as they may cause hirsutism.
• Gonadotropin Releasing Hormone (GnRH) agonist: These agents work by increasing the levels of GnRH. Consistent stimulation of the GnRH receptors results in downregulation, inducing a profound hypoestrogenism by decreasing FSH and LH levels. While quite effective, they induce unpleasant menopausal symptoms, and over time may lead to osteoporosis. To counteract such side effects some estrogen may have to be given back (add-back therapy).
  • Lupron depo shot is a GnRH agonist and is used to lower the hormone levels in the woman's body to prevent or reduce growth of endometriosis. The injection is given in 2 different doses a once a month for 3 month shot with the dosage of (11.25mg) or a once a month for 6 month shot with the dosage of (3.75mg).^[16]
• Aromatase inhibitors are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis.^[17]

Surgery

Although medicine is extensively used for this condition, the most effective treatment is surgical ^[18]

• Conservative therapy is usually applied in women where the reproductive potential needs to be maintained and consists of removal or ablation of endometriosis, adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible. It is important to preserve healthy ovarian tissue as much as possible.^[2] The approach can be either by laparoscopy or laparotomy, however as laparoscopy is already used to diagnose endometriosis the surgical correction can often be performed at the same session. Further, laparoscopy has a faster recovery time and involves less hospitalization. Laparoscopic removal or ablation of endometriosis in minimal or mild endometriosis has been shown to be equal or better then expectant management, medical therapy, or surgery via laparotomy.^[19] Radical therapy in endometriosis removes the uterus (Hysterectomy) and tubes and ovaries (bilateral salpingo-oophorectomy) and thus the chance for reproduction. Modifications of this approach involve preserving a healthy appearing ovary, however, this will increase the risk of recurrence.^[20] Radical surgery is generally reserved for women with chronic pelvic pain that is disabling and treatment-resistant. Not all patients with radical sugery will become pain-free. The history of endometriosis is not a contraindication to the use of hormone replacement therapy as the estrogen dose in HRT is low.
• For patients with extreme pain, a presacral neurectomy may be indicated where the nerves to the uterus are cut. However, strong clinical evidence showed that presacral neurectomy is more effective in pain relief if the pelvic pain is midline concentrated, and not as effective if the pain extends to the left and right lower quadrants of the abdomen.^[2] This is due to the fact that the nerves to be transected in the procedure are innervating the central or the midline region in the female pelvis. Furthermore, women who had presacral neurectomy have higher prevalence of chronic constipation not responding well to medication treatment because of the potential injury to the parasympathetic nerve in the vicinity during the procedure.

Alternative and complementary medicine

Complementary and Alternative medicine are used by many women to get relief from the pain and discomforts from a variety of available treatments.

• Serotonin modulation is an approach to pain management that has been advocated for women suffering from endometriosis. involves raising one's serotonin levels. Low serotonin levels reduce the pain threshold, and make people more susceptible to pain.
• In Asia, especially Korea and Northern China, herbal formulas are prescribed to help the body regulate the abnormal cellular growth that causes endometriosis. In the US, the same formula is commonly called, Endomet.
• Nutrition: There has been research showing that prostaglandins series 1 and 3 have an anti-inflammatory effect which can help with endometriosis. Proper nutrition may also help to boost the immune system, which could be helpful if immune deficiencies contribute to endometriosis.
• Coffee and alcohol should be avoided as both can increase the levels of estrone.
• It has been suggested that endometriosis is an auto-immune condition and if the immune system is compromised with a food intolerance, then removing that food from the diet can, in some people, have an effect. Common intolerances in people with endometriosis are wheat and dairy.^[21]
• While it can't cure endometriosis, acupuncture can be used as a palliative to treat the pain associated with menstrual cramps, back symptoms, and endometriosis adhesions.
• Physical therapy for pain management in endometriosis has been investigated in a pilot study suggesting possible benefit.^[22]

Treatment of infertility

Laparoscopy to remove or vaporize the growths in women who have mild or minimal endometriosis is effective in improving fertility. One study has shown that surgical treatment of endometriosis approximately doubles the fecundity (pregnancy rate).^[19] The use of medical suppression after surgery for minimal/mild endometriosis has not shown benefits for patients with infertility.^[3] Use of fertility medication that stimulates ovulation (clomiphene citrate, gonadotropins) combined with intrauterine insemination (IUI) enhances fertility in these patients.^[3]

In-vitro fertilization (IVF) procedures are effective in improving fertility in many women with endometriosis. IVF makes it possible to combine sperm and eggs in a laboratory and then place the resulting embryos into the woman's uterus. The decision when to apply IVF in endometriosis-associated infertility takes into account the age of the patient, the severity of the endometriosis, the presence of other infertility factors, and the results and duration of past treatments.

Prognosis

Proper counseling of patients with endometriosis requires attention to several aspects of the disorder. Of primary importance is the initial operative staging of the disease to obtain adequate information on which to base future decisions about therapy. The patient's symptoms and desire for childbearing dictate appropriate therapy. Not all therapy works for all patients. Some patients have reoccurrences after surgery or pseudo-menopause. In most cases, treatment will give patients significant relief from pelvic pain and assist them in achieving pregnancy.^[23] It is important for patients to be continually in contact with their physician and keep an open dialog throughout treatment. This is a disease without a cure but with the proper communication, one with endometriosis can attempt to live a normal, functioning life.

Recurrence

The underlying process that causes endometriosis may not cease after surgical or medical intervention, and the annual recurrence rate is given as 5-20 % per year reaching eventually about 40% unless hysterectomy is performed or menopause reached.^[2] Monitoring of patients consists of periodid clinical examinations and sonography. Also, the CA 125 serum anitgen levels have been used folow patients with endometriosis.

Relation to cancer

Endometriosis bears no relationship to endometrial cancer. Current research has demonstrated an association between endometriosis and certain types of cancers, notably ovarian cancer and brain cancer.^[24][25] Endometriosis often also coexists with leiomyoma or adenomyosis, as well as autoimmune disorders.

Endometriosis in the male

Endometriosis has been described in a male who received a very high estrogen medication (TACE) as part of treatment for prostatic cancer.^[26]

Additional images

<gallery> Image:Endometriosis, abdominal wall.jpg|Endometriosis, abdominal wall </gallery>

See also

• Ovarian cyst (Endometrioid cyst)

References

External links

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