Endometriosis reference

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Endometriosis is a common medical condition characterized by growth beyond or outside the uterus of tissue resembling endometrium, the tissue that normally lines the uterus.

Affecting an estimated 89 million women of reproductive age (those who have yet to become pregnant) around the world, endometriosis occurs in one in every five women.[1][citation needed] However, endometriosis can occur very rarely in postmenopausal women.[1] An estimated 2%-4% of endometriosis cases are diagnosed in the postmenopausal period.

In endometriosis, the endometrium (from endo, "inside", and metra, "womb") is found to be growing outside the uterus, most commonly in the pelvis.

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Locations

Endometriosis most commonly exists in the lower region of the female pelvis. The most common site of disease is the ovary (approximately half of the cases). The broad ligaments (beneath the ovaries), uterosacral ligaments (supporting structures of the cervix containing sensory nerves from the uterus) and pouch of Douglas (peritoneum between the rectum and the cervix) are the most frequently involved areas and can produce intense to no pain[2] felt in the pelvis, low back, and during premenstrual period. Less commonly lesions can be found on the bladder, intestines, ureters, and diaphragm. Bowel endometriosis affects approximately 10% of women with endometriosis, and can cause severe pain with bowel movements. Diaphragmatic endometriosis is rare, most always on the right hemidiaphragm, and causes severe cyclic pain of the right shoulder just before and during menses. Very rarely endometriosis is found distant from pelvis, in sites such as the lung, brain, and kidney. Pleural implantations are associated with recurrent right pneumothoraces at times of menses, termed catamenial pneumothorax. Similarly, lesions in the central nervous system can cause catamenial seizures.

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Symptoms

A major symptom of endometriosis is severe recurring 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 endometriosis can include (but are not limited to):

* dysmenorrhea - Painful, sometimes disabling menstrual cramps; pain may get worse over time (progressive pain)
* Chronic pelvic pain - typically accompanied by lower back pain and/or abdominal pain.
* dyspareunia - Painful sex
* dyschezia - Painful bowel movements
* Nausea, vomiting, and/or diarrhea
* dysuria - Urinary urgency, frequency, and sometimes painful voiding
* Infertility and subfertility. Endometriosis may lead to fallopian tube obstruction. Even without this, there may be difficulty conceiving. In some women, subfertility is the sole symptom, and the endometriosis is only discovered after fertility investigations.
* frequent menses flow or short menstrual cycle.
* 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. Endometriotic cysts in the thoracic cavity may cause some form of thoracic endometriosis syndrome, most often catamenial pneumothorax.

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Frequency
“ In the US: Endometriosis occurs in 7-10% of women in the general population (Wheeler, 1989). It is an estrogen-dependent disease and, thus, usually affects reproductive-aged women. Endometriosis has a prevalence rate of 20-50% in infertile women (Rawson, 1991; Strathy, 1982; Verkauf, 1987) and as high as 80% in women with chronic pelvic pain (Carter, 1994). Evidence of endometriosis was found during laparoscopy in 20-50% of asymptomatic women (Williams, 1977). Approximately 4 per 1000 women are hospitalized with endometriosis each year. A familial association exists, with a 10-fold increased incidence in women with an affected first-degree relative (Cramer, 1987).... Monozygotic twins are markedly concordant for endometriosis (Hadfield, 1997).[3] ”

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Epidemiology

Endometriosis can affect any woman, from premenarche to postmenopause, regardless of her race, ethnicity or whether or not she has had children. Endometriosis often persists after menopause. Endometriosis in postmenopausal women is an extremely aggressive form of this disease characterized by complete progesterone resistance and extraordinarily high levels of aromatase expression.[4] A majority of 50 postmenopausal women diagnosed with endometriosis had no previous history of the disease. In less common cases, girls may have endometriosis before they even reach menarche.[5][6]

Current estimates place the number of women with endometriosis at between 5% and 20% of women of reproductive age. About 30% to 40% of women with endometriosis are infertile, making it one of the leading causes of infertility. However, endometriosis-related infertility is often treated successfully with surgical destruction of the disease. Some women do not find out that they have endometriosis until they have trouble getting pregnant. While the presence of extensive endometriosis distorts pelvic anatomy and thus explains infertility, the relationship between early or mild endometriosis and infertility is less clear. The relationship between endometriosis and infertility is an active area of research.

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 structures in the pelvic cavity:

* Ovaries
* 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, particularly the appendix
* Urinary bladder

Endometriosis may spread to the cervix and vagina or to sites of a surgical abdominal incision. In extremely rare cases, endometriosis areas can grow in the lungs or other parts of the body.

Surgically, endometriosis can be staged I-IV (Revised Classification of the American Society of Reproductive Medicine).[7]

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Theories of Origin

There are two major theories of origin that are commonly accepted within the scientific community. Sampson's theory is that of reflux menstruation. According to this theory, every month during a woman's menstrual flow, endometrial cells slough normally, then exit the uterus through the fallopian tubes, attach to the peritoneal surface (the lining of the abdominal cavity) and then invade to cause the disease of endometriosis. There are many problems with this theory, these are just a few:

1. Most women have some degree of reflux menstruation, yet only 10-15% of them have endometriosis;
2. Endometriosis follows reproducible patterns of distribution within the pelvis, and older women do not have more widespread disease than younger women as one would expect if reflux menstruation was truly the origin;
3. More than 700 gene differences exist between the tissue found in endometriosis and native endometrium, which should not be the case if endometriosis is an autotransplant disease formed by reflux menstruation;
4. Conservative surgical excision of endometriosis (removing the disease without removing the uterus or ovaries) produces a cure rate of approximately 60% which would be impossible if Sampson's theory were true, because every month new endometriosis would form as long as a woman kept menstruating;
5. Sampson's theory cannot explain endometriosis of distant sites including the brain, lungs, and skin.

Because of these inconsistencies, another theory has been proposed, that of Embryologically patterned metaplasia. This theory states that cells destined 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.

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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. Endometriosis is a condition caused by excess estrogen created each month in the female body, and is seen primarily during the reproductive years. In experimental models, excess estrogen is necessary to induce or maintain endometriosis. Medical therapy is often aimed at lowering estrogen levels to control the disease. It is hypothesized that excess estrogen levels may be measured by a female taking her morning temperature (with a thermometer showing a tenth decimal) at the same time each day for a month or two. A normal woman's body temperature varies from 97.5 to 98.5 degrees Fahrenheit (36.3 to 36.9 degrees Celsius), however it is hypothesized that someone with endometriosis may see temperatures of 97.0 to 98.5 °F (36.1 to 36.9°C). The lower temperatures signify the estrogen phase of a normal female's cycle, therefore it is logical that women with excessively lower body temperatures, may have an excess of estrogen, thus endometriosis. Research is needed to determine the reliability of using waking temperatures to diagnose endometriosis and its severity. 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", in which some of the menstrual debris of menstruation flows into the pelvis, may play an important role (John A. Sampson). 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 is 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.
3. 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. Triggers of various kind (including menses, toxins, or immune factors) may be necessary to start this process.
4. 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. A recent study (2005) published in the American Journal of Human Genetics found a link between endometriosis and chromosome 10q26.[8] One study found that, in female siblings of patients with endometriosis the relative risk of endometriosis is 5.7:1 versus a control population.[9]
5. It is accepted that in specific patients endometriosis can spread directly. Thus endometriosis has been found in abdominal incisional scars after surgery for endometriosis.
6. On rare occasions endometriosis may be transplanted by blood or by the lymphatic system into peripheral organs (e.g. lungs, brain).
7. Recent 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.[10] However it is still unclear what, if any, causal relationship exists between toxins, autoimmune disease, and endometriosis.
8. 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.[2] Other sources suggest that pesticides and hormones in our food cause a hormone imbalance.

Another 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,[11] but not specifically indicative of endometriosis.

A small-scale 1995 study by University of Louisville School of Medicine suggests "an association between the occurrence of natural red hair and those factors that lead to the development of endometriosis".[12]

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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.

Generally, endometriosis-directed drug therapy is utilized after a confirmed surgical diagnosis of endometriosis.

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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.

Endometriosis is thought to be 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.

Women with endometriosis frequently suffer from painful ovarian cysts, making ovulation quite painful. Sometimes, the cysts burst and can cause life-threatening infections in the pelvic cavity.

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 more debilitating on a daily basis than the menstrual symptoms.

When a woman suffers from endometriosis long enough, the pain may go from the original site to include back pain as well.[citation needed]

In addition to pain caused by the disease directly, surgical treatment can also be quite painful. Laparoscopy, laparotomy, hysterectomy, oophorectomy, bowel and bladder surgeries are all common.

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Treatments

Currently, there is no known cure for endometriosis, though in some patients menopause (natural or surgical) will abate the process. Nevertheless, a hysterectomy and/or removal of the ovaries will not guarantee that the endometriosis areas and/or the symptoms of endometriosis will not come back, since adhesions can be found on other organs besides the reproductive organs and even on the abdominal walls. Surgical treatment tends to be conservative, with the goal of addressing pain or infertility issues through removal of the endometriosis tissue without damaging normal tissue.

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

Other treatments for endometriosis pain include:

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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.
* Hormone suppression therapy: This approach tries to reduce or eliminate menstrual flow and estrogen support. Typically, it needs to be done for several months or even years.
* 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.
* 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. There has been some research done at Case Western Reserve University on a topical Danocrine, applied locally, which has not produced the hirsutism characteristics. The study has not yet been published in a medical journal.
* 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, thereby decreasing estrogen and progesterone 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).
* Aromatase inhibitors are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis.[14]
* Lupron depo shot is also a gonadotropin and is used to lower the hormone levels in the woman's body to prevent any growth of endometriosis. The lupron shot 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). This puts the body into a "medicated menopause", resulting in side effects such as mild to severe hot flashes or a drop in bone density (which usually recovers after treatment).[15] The therapy is less invasive than surgical approaches.

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Surgery

Surgical treatment is usually a good choice if endometriosis is extensive, or very painful. Surgical treatments range from minor to major surgical procedures.

* Laparoscopy is very useful not only to diagnose endometriosis, but to treat it. With the use of scissors, cautery, lasers, hydrodissection, or a sonic scalpel, endometriotic tissue can be ablated or removed in an attempt to restore normal anatomy. Studies have shown that with true excision, recurrence rates are less than 20%.
* Laparotomy can be used for more extensive surgery either in attempt to restore normal anatomy, or at least preserve reproductive potential.
* Hysterectomy (removal of the uterus and surrounding tissue) and bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries). Hysterectomy and bilateral salpingo-oophorectomy is the definitive treatment for endometriosis.
* Bowel resection can be useful if there is bowel involvement.
* 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. 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.

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avoid:
Complementary or 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.
* Medical herbal treatments are sometimes used to try to control the disease.
* Nutrition: There has been research[citation needed] 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.[citation needed]
* Some women with gluten sensitivity may be helped by avoiding wheat and wheat products.[citation needed]
* 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

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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 reoccurances after surgery or pseudo-menopause. Most patients can be told that they will be able to obtain significant relief from pelvic pain and that treatment will assist them in achieving pregnancy.[1] It is important for patients to be continually in contact with their physician and keep an open dialog throughout treatment. Unfortunately, this is a disease without a cure but with the proper communication, one with endometriosis can attempt to live a normal, functioning life.

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Complications

The main complication of endometriosis is impaired fertility. Approximately one-third to one-half of women who have difficulty becoming pregnant have endometriosis.

For pregnancy to occur, an egg must be released from an ovary and travel through the fallopian tube to the uterus (womb), where it can be fertilized by a male's sperm and then attach to the uterine wall to begin development. Endometriosis can produce adhesions that can trap the egg near the ovary. It may inhibit the mobility of the fallopian tube and impair its ability to pick up the egg. In most cases, however, endometriosis probably interferes with conception in more complex ways.

Other complications include:

* Internal scarring
* Adhesions
* Pelvic cysts
* Chocolate cysts
* Ruptured cyst
* Infertility - occurs in about 30-40% of cases.

Complications of endometriosis consist of bowel and ureteral obstruction resulting from pelvic adhesions. Rarely, endometriosis can be extraperitoneal and is found in the lungs and CNS.[16]

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Infertility

Endometriosis is associated with a lowered fertility and is the second leading cause of infertility in females that ovulate normally (the leading cause is pelvic inflammatory disease).

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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).[17]

In patients with small amounts of endometriosis treatment with fertility medication clomiphene may lead to success. This drug stimulates ovulation.

Lipiodol flushing may increase fecundity.

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. IVF is one type of assisted reproductive technology that may be an option for women and families affected by infertility related to endometriosis.

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Relation to cancer

Endometriosis is not the same as endometrial cancer. However it is hypothesized that the excess estrogen creation by endometriosis may eventually cause ovarian or other cancers over a woman's lifetime.[citation needed] The staging of endometriosis is similar to the staging of cancers, as well, in the sense that they both gauge the spread of disease in a similar fashion to different zones of the body. Current research has demonstrated an association between endometriosis and certain types of cancers.[18][19] Endometriosis often also coexists with leiomyoma or adenomyosis, as well as autoimmune disorders