Endometriosis

Endometriosis is a common medical condition affecting an estimated 89 million women of reproductive age around the world. With Endometriosis, tissue like that which lines the uterus (the endometrium, from endo, "inside", and metra, "womb") is found outside the womb in other areas of the body. Normally, the endometrium is shed each month through menses; however, with Endometriosis, the misplaced endometrium has no way of leaving the body. The tissues still break down and bleed, but result is far different in women and girls without the disease: internal bleeding, degeneration of blood and tissue shed from the growths, inflammation of the surrounding areas, and formation of scar tissue result. In addition, depending on the location of the growths, interference with the normal function of the bowel, bladder, intestines and other areas of the pelvic cavity can occur. Endometriosis has also been found lodged in the skin, the lungs, the diaphragm and even the brain.

Symptoms
A major symptom of endometriosis is pain, mostly in the lower abdomen, lower back, and pelvic area. 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 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 intercourse (dyspareunia)
 * Painful bowel movements 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.

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 of reproductive age, from menarche (the first period) to menopause, regardless of her race, ethnicity, whether or not she has children or her socio-economic status. Most patients with endometriosis are in their 20s and 30s. Endometriosis persists after menopause; sometimes, hormones taken for menopausal symptoms may cause the symptoms of endometriosis to continue. In very rare cases, girls may have endometriosis before they even reach menarche.

Current estimates place the number of women with endometriosis between 2 % and 10 % 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 hormones and surgery. 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
 * 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 explain its development. These concepts do not necessarily exclude each other.


 * 1) Endometriosis is an estrogen-dependent condition, as it is seen during the reproductive years and generally disappears after menopause. In experimental models, estrogen is necessary to induce or maintain endometriosis. Medical therapy is often aimed at lowering estrogen levels to control the disease.  However, 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", by which some of the menstrual debris from the period 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 prevents 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, i.e. hereditary factors, toxins,  or a compromised immune system. It can be argued that the uninterrupted occurrence of regular menstruation over decades month after month is a modern phenomenon, as in the past women had more frequent menstrual rest due to pregnancy or 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 to develop 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 (i.e. lungs, brain).
 * 7) Recent research is focusing on the immune system that may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest to study relationship to autoimmune disease, allergy 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 or urine. If markers are found, health care providers could diagnose endometriosis by testing a woman's blood or urine, 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 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, or keyhole 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 (other than the oral contraceptive pill) is utilized after a confirmed surgical diagnosis of endometriosis.

Cause of pain
How 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 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.

Treatments
Currently, there is no cure for endometriosis, though in some patients menopause (natural or surgical) will abate the process. Nevertheless, a hysterectomy or removal of the ovaries will not guarantee that the endometriosis areas and/or the symptoms of endometriosis will not come back. However, endometriosis can be effectively managed in a large majority of patients. Conservative treatments usually try to address pain or infertility issues.

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 have to be used.
 * Gonadotrophin 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 testosterone levels
 * 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 birth control pills consists of the use of birth control pills without the use of placebo pills. This eliminates monthly bleeding episodes.
 * Danazol (Danocrine) and gestrinone are a suppressive steroids with some androgenic activity. Both agents inhibits 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 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.
 * Laparotomy can be used for more extensive surgery either in attempt to restore normal anatomy, or at least preserve reproductive potential.
 * The definitive treatment for endometriosis is a total hysterectomy (removal of the uterus and surrounding tissue) and bilateral salpingoophorectomy (removal of the uterine tubes and ovaries).
 * For patients with extreme pain, a presacral neurectomy may be indicated where the nerves to the uterus are cut.
 * A variety of alternative treatments are being used in patients with endometriosis, including acupuncture and nutrition.

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. Current research has not demonstrated an association between endometriosis and endometrial, cervical, uterine, or ovarian cancers. In very rare cases ( much less than one percent), endometriosis is seen with endometrioid cancer, but there is no evidence of a causal role between one and the other. Endometriosis often coexists with leiomyoma or adenomyosis.