Endometriosis

For patient information, click here

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

Affecting an estimated 89 million women (usually around 30 to 40 years of age who have never been pregnant before) of reproductive age around the world, one in every 5 females get endometriosis.. However, endometriosis can occur very rarely in postmenopausal women. 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, on or in other areas of the body. Normally, the endometrium is shed each month during the menstrual cycle; however, in endometriosis, the misplaced endometrium is usually unable to exit the body. The endometriotic tissues still detach and bleed, but the result is far different: internal bleeding, degenerated blood and tissue shedding, inflammation of the surrounding areas, pain, and formation of scar tissue may result. In addition, depending on the location of the growths, interference with the normal function of the bowel, bladder, small intestines and other organs within the pelvic cavity can occur. In very rare cases, endometriosis has also been found in the skin, the lungs, the eye, the diaphragm, and the brain.

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):
 * Painful, sometimes disabling menstrual cramps (dysmenorrhea); pain may get worse over time (progressive pain)
 * Chronic pain (typically lower back pain and pelvic pain, also abdominal)
 * Painful sex (dyspareunia)
 * Painful bowel movements (dyschezia) or painful urination (dysuria)
 * Heavy menstrual periods (menorrhagia)
 * Nausea and vomiting
 * Premenstrual or intermenstrual spotting (bleeding between periods)
 * 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.
 * Bowel obstruction (possibly including vomiting, crampy pain, diarrhea, a rigid and tender abdomen, and distention of the abdomen, depending on where the blockage is and what is causing it) or complete urinary retention.

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

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.

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. 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.

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 intraabdominal 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
 * 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).

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. To learn more about taking your waking temperature, please see the book: "Taking Charge of Your Fertility" by Toni Weschler, MPH. A normal woman's body temperature varies from 98.5 to 97.5 degrees Fahrenheit (36.9 to 36.3 degrees Celsius), however it is hypothesized that someone with endometriosis may see temperatures of 98.5 to 97.0 °F (36.9 to 36.1 °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. A recent study (2005) published in the American Journal of Human Genetics found a link between endometriosis and chromosome 10q26. One study found that, in female siblings of patients with endometriosis the relative risk of endometriosis is 5.7:1 versus a control population.
 * 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.

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, urine, or daily waking temperature. If markers are found, health care providers could diagnose endometriosis by testing a woman's blood, urine, or daily waking temperature, which might reduce the need for surgery. CA-125 is known to be elevated in many patients with endometriosis, but not specifically indicative of endometriosis.

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

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 sure way to confirm an endometriosis diagnosis is by laparoscopy. 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 (other than the oral contraceptive pill) is utilized after a confirmed surgical diagnosis of endometriosis.

Cause of pain
The way endometriosis causes pain is the topic 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.

Treatments
Currently, there is no 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. Conservative treatments usually try to address pain or infertility issues. Medical herbal treatments can sometimes be effective in controlling the disease.

The treatments for endometriosis pain include:


 * NSAIDs and other pain medication: They often work quite well as they not only reduce pain but also menstrual flow. They are commonly used in conjunction with other therapy. For more severe cases narcotic prescription drugs may be used.
 * Gonadotropin Releasing Hormone (GnRH) Agonist: These agents work by increasing the levels of GnRH. Consistent stimulation of the GnRH receptors results in downregulation.  This causes a decrease in FSH and LH, thereby decreasing estrogen and progesterone levels.
 * It is suggested but unproven that pregnancy and childbirth can stop endometriosis.
 * 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 agonists (GnRH agonists) induce 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).
 * Aromatase inhibitors are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis.


 * 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  such as the Redwine Method, 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).
 * 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.


 * Raising your serotonin level: low serotonin levels reduce the pain threshold, and make people more vulnerable to every pain. Women particularly need adequate amounts of light during the second half of their menstrual cycles, when their serotonin levels may already be low.
 * Many people like sweets: eating sugar or chocolate temporarily increases serotonin levels, but creates a rebound effect, characterized by heightened PMS symptoms.
 * Melatonin and serotonin are increased by meditation, and the stress hormone cortisol is decreased. Melatonin causes you to go into delta-sleep, during which period Human Growth Hormone is released. As melatonin levels drop from childhood (100%) to age 20 (30%) and age 30 (20%), recovering takes more time, so good deep sleep is essential.
 * Serotonin is manufactured by the body from a partial protein or amino acid called tryptophan. This amino acid is found in many foods, including soy, turkey, chicken, halibut, and beans.
 * Lavender, primarily in the form of oil, has been found to reduce several physiological parameters of stress by stimulating serotonin and inducing a feeling of calm and happiness.
 * Light therapy increases your serotonin levels.


 * Complementary or Alternative medicine are used by many women who get great relief from the pain and discomforts from a variety of available treatments.
 * Nutrition: There has been research showing that prostaglandins series 1 and 3 have an anti inflammatory effect which can help with endometriosis. Nutrition can also help to boost the immune system, which is important if endometriosis is an auto-immune disorder.
 * Avoid coffee and alcohol. Both can increase the levels of estrone.
 * In many cases, marijuana (cannabis sativa) has proven to relax or suppress the pain and relieve stress. Although doctors consider this to be an unorthodox method given all the treatments available for this condition and the fact that it may not produce any long term effects, this may still be an effective way to combat endometriosis. Research on this method is minimal since the drug is illegal in many countries.

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. 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.

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.


 * 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.

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).

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).

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

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.

Relation to cancer
Endometriosis is not the same as endometrial cancer. However it is hypothesized that the excess estrogen creation and abnormal cell growth caused by endometriosis may eventually cause ovarian or other cancers over a woman's lifetime. 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. Endometriosis often also coexists with leiomyoma or adenomyosis, as well as autoimmune disorders.