Endometriosis


Endometriosis is a disease in which tissue similar to the lining of the uterus grows elsewhere in the body. The tissue most often grows on or around the ovaries and fallopian tubes, on the outside surface of the uterus, or the tissues surrounding the uterus and the ovaries. It can also appear on the bowel, bladder, or, rarely, on the lungs and skin.
Symptoms vary widely between individuals. Some have no symptoms, while for others it can be a debilitating disease. Common symptoms include pelvic pain, heavy and painful periods, pain with bowel movements, painful urination, pain during sexual intercourse, and infertility. Beyond physical symptoms, endometriosis can affect a person's mental health and social life.
A presumed diagnosis can be made based on symptoms and medical imaging; a laparoscopy provides definite confirmation. Other causes of similar symptoms include adenomyosis, uterine fibroids, irritable bowel syndrome, and interstitial cystitis. Endometriosis is often misdiagnosed and many patients report being incorrectly told their symptoms are trivial or normal. On average, it takes 5–12 years from the start of symptoms to receive a diagnosis.
Worldwide, endometriosis affects approximately 10% of the female population of reproductive age, representing about 190 million women. Asian women are more likely than White women to be diagnosed. The exact cause is not known. Possible causes include backwards menstrual period flow, genetic factors, hormones, and problems with the immune system.
While there is no cure for endometriosis, several treatments may improve symptoms. This includes pain medication, hormonal treatments or surgery. The recommended pain medication is usually a non-steroidal anti-inflammatory drug, such as naproxen. Taking the birth control pill continuously or using a hormonal IUD is another first-line treatment. Other types of hormonal treatment can be tried if the pill or IUD are not effective. Endometriosis can be removed surgically in women whose symptoms are not relieved by other treatments or to help with infertility.

Subtypes

Endometriosis can be subdivided into four categories:
; Superficial peritoneal endometriosis
; Deep infiltrating endometriosis
; Endometriomas
; Extrapelvic endometriosis
Endometriosis most commonly affects the ovaries, the fallopian tubes between the ovaries and the uterus, the outer surface of the uterus and the tissues that hold the uterus in place. Less common pelvic sites are the rectum, bladder, bowel, vulva, vagina and cervix. Endometriomas appear dark brown, giving rise to the name "chocolate cysts", and are filled with old menstrual blood among other material. When lesions grow more than 5 mm beneath the peritoneal surface, they are classified as deep infiltrating endometriosis. It can infiltrate the muscles around organs. Deep endometriosis often appears as nodules, and can include fibrosis and adhesions.
Rarely, endometriosis appears on the lungs, brain, and skin. Diaphragmatic endometriosis forms almost always on the right hemidiaphragm, and may cause the cyclic pain of the right shoulder or neck during a menstrual period. Scar endometriosis can rarely form on the abdominal wall as a complication of surgery, most often following a ceasarean section or other pelvic surgery.

Signs and symptoms

Endometriosis is often associated with pain and infertility. Some women with endometriosis do not have any symptoms, while for others the pain is life-altering. The amount of pain relates poorly to the anatomical extent of endometriosis. Those with 'minimal' endometriosis may have significant pain, while those with 'severe' endometriosis might have few symptoms.
The most frequent symptom of endometriosis is pelvic pain, which includes:
Women with endometriosis are about twice as likely to experience infertility compared to other women. Between 16% and 40% of women with endometriosis experience difficulty conceiving. In those going through assisted reproductive treatment, endometriosis is found in about 30% to 50% of women. The World Health Organization estimates that endometriosis is the ultimate cause of female infertility in 4.8% of cases.
Endometriosis can involve symptoms like constipation, diarrhea, nausea, bloating, rectal or abdominal pain. This is sometimes caused by endometriosis on the bowels, but often due to co-occurring irritable bowel syndrome. People with endometriosis often experience fatigue, which is linked to insomnia, depression and anxiety.
Thoracic endometriosis occurs when endometrium-like tissue implants in the lungs or pleura around the lungs. It is rare. When it occurs in the lungs, common signs and symptoms are blood discharge from the lungs during menstruation and nodules which become bigger during menstruation. When it is found in the pleura, symptoms may be a collapsed lung during or outside of menstruation and bleeding into the pleural space. Further symptoms are a cyclical cough and cyclical shoulder pain. Most often, the endometriosis is found in the right lung. Blood in urine may point to endometriosis in the bladder or in the ureter. Sciatic endometriosis is a rare form in which endometrial tissue involves the sciatic nerve, causing cyclic nerve pain in the leg.

Complications

Endometriosis may be associated with complications during pregnancy. Women with endometriosis have a three-fold increased risk of a placenta previa, in which the placenta partially or completely covers the cervical opening. Preterm delivery was almost 50% more likely. Other complications are stillbirth, gestational hypertension, pre-eclampsia, and placental abruption.
Cardiovascular disease is also associated with endometriosis, in particular in those who have had a surgical removal of the uterus and ovaries. Cohort studies have found associations with strokes, heart attacks, high blood pressure and arrhythmia. Depression and anxiety are more common in endometriosis compared to healthy controls, but occur at the same rate as with other chronic pain conditions. It is unclear how much this is caused by shared underlying mechanisms, the impact of severe symptoms, stigma, the related diagnostic delays or the ineffectiveness of treatment.

Risk factors

Genetics

Inheritance is significant but not the sole risk factor for endometriosis. Studies attribute 50% of the risk to genetics, the other 50% to environmental factors. At least 42 different loci have been associated with endometriosis risk. The genes linked to endometriosis risk help control cancer-related processes, sex-hormone signals, womb development, molecules related to inflammation and adhesions, and the growth of new blood vessels.
There is significant overlap between the genetic basis of endometriosis, other pain conditions and inflammatory conditions. For instance, endometriosis shares a genetic underpinning with migraine and neck, shoulder and back pain. Among inflammatory conditions, it shares variants with asthma and osteoarthritis.

Reproductive and environmental factors

People whose menstrual outflow is obstructed are at risk of developing endometriosis. This could be because of an imperforate hymen, or a double uterus with a blocked hemivagina. Other risk factors are having a first period before age 12, a menstrual cycle of fewer than 28 days, a low BMI, and not having had children.
Little is known about environmental risk factors. Night work and red meat consumption seems to raise risk, as does exposure to some classes of environmental pollutants. The most studied of these are endocrine disruptors—chemicals that interfere with hormones, such as estrogen. They include dioxins, phthalates, bisphenol A and polychlorinated biphenyl. Based on epidemiological and experimental data, it is possible that exposure to some of them increases the risk of endometriosis.

Mechanism

Endometriosis is an inflammatory disease dependent on estrogen. The lesions promote local inflammation and immune system dysregulation. They also trigger the formation of adhesions and fibrosis. It is not well understood how endometriosis causes infertility and pain.

Formation

Origin of endometriosis cells

The main theories for the formation of the endometrium-like tissue outside the womb are backward flow of menstrual blood, metastasis via the lymphatic or the circulatory system and local transformation of peritoneal cells into endometrial-like cells.
During menstruation, some menstrual blood, tissue, and fluid can flow backward through the fallopian tubes into the pelvic area. This backward flow is thought to be the main reason why endometriosis develops inside the pelvic cavity. However, this explanation alone is not enough, because almost all women have some backward flow of menstrual fluid, but only some of them develop endometriosis.
Evidence supporting the theory comes from retrospective epidemiological studies and DNA analysis. Furthermore, only animals with a menstrual cycle such as rhesus monkeys and baboons develop endometriosis. In contrast, animals like rodents and non-human primates with an estrous cycle in which the endometrium is reabsorbed rather than shed do not develop the disease.
Endometriosis has been documented in men, prepubescent girls, and in female fetuses, demonstrating that menstruation is not required for the condition to develop. One explanation for endometriosis in girls before puberty is coelomic metaplasia: the theory that certain cells in the peritoneum may undergo metaplasia into endometrium-like cells. Müllerian remnants, cells that normally disappear during male embryonic development, may explain rare cases of endometriosis in men. Metastasis via the lymphatic or the circulatory system may explain endometriosis outside of the pelvic region.
Stem cells may contribute to the formation of endometriosis. Stems cells in the basal layer of the endometrium play a role in renewing the tissue after menstruation. In women with endometriosis, more tissue is shed from this layer during menstruation, allowing more stem cells to flow back into the peritoneum with retrograde menstruation, and form lesions. Stem cells from bone marrow may drive the further growth of lesions, and also explain the establishment of endometriosis outside of the pelvic region.