endometriosis endometriosis endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. lesions can be found on ovaries, fallopian tubes, tissue around the uterus and ovaries (peritoneum), intestines, bladder, and diaphragm; it may also occur in other parts of the body. some symptoms include pelvic pain, heavy periods, pain with bowel movements, painful urination, and infertility. nearly half of those affected have chronic pelvic pain, while in 70% pain occurs during menstruation. pain during sexual intercourse is also common. infertility occurs in up to half of affected individuals. about 25% of individuals have no symptoms and 85% of those seen with infertility in a tertiary center have no pain. endometriosis can have both social and psychological effects. not to be confused with endometritis. endometriosisendometriosis as seen during laparoscopic surgeryspecialtygynecologysymptomspelvic pain, infertilityusual onset20-40 years olddurationlong termcausesunknownrisk factorsfamily historydiagnostic methodbased on symptoms, medical imaging, tissue biopsydifferential diagnosispelvic inflammatory disease, irritable bowel syndrome, interstitial cystitis, fibromyalgiapreventioncombined birth control pills, exercise, avoiding alcohol and caffeinetreatmentnsaids, continuous birth control pills, intrauterine device with progestogen, surgeryfrequency10.8 million (2015)deaths≈100 (0.0 to 0.1 per 100,000, 2015) the cause is not entirely clear. risk factors include having a family history of the condition. the areas of endometriosis bleed each month (menstrual period), resulting in inflammation and scarring. the growths due to endometriosis are not cancer. diagnosis is usually based on symptoms in combination with medical imaging; however, biopsy is the surest method of diagnosis. other causes of similar symptoms include pelvic inflammatory disease, irritable bowel syndrome, interstitial cystitis, and fibromyalgia. endometriosis is commonly misdiagnosed and females often report being incorrectly told their symptoms are trivial or normal. females with endometriosis see an average of seven physicians before receiving a correct diagnosis, with an average delay of 6.7 years between the onset of symptoms and surgically obtained biopsies, the gold standard for diagnosing the condition. this average delay places endometriosis at the extreme end of diagnostic inefficiency. tentative evidence suggests that the use of combined oral contraceptives reduces the risk of endometriosis. exercise and avoiding large amounts of alcohol may also be preventive. there is no cure for endometriosis, but a number of treatments may improve symptoms. this may include pain medication, hormonal treatments or surgery. the recommended pain medication is usually a non-steroidal anti-inflammatory drug (nsaid), such as naproxen. taking the active component of the birth control pill continuously or using an intrauterine device with progestogen may also be useful. gonadotropin-releasing hormone agonist (gnrh agonist) may improve the ability of those who are infertile to get pregnant. surgical removal of endometriosis may be used to treat those whose symptoms are not manageable with other treatments. one estimate is that 10.8 million people are affected globally as of 2015. other sources estimate 6 to 10% of the general female population and 2 to 11% of asymptomatic women are affected. in addition, 11% of women in a general population have undiagnosed endometriosis that can be seen on magnetic resonance imaging (mri). endometriosis is most common in those in their thirties and forties; however, it can begin in girls as early as eight years old. it results in few deaths with unadjusted and age-standardized death rates of 0.1 and 0.0 per 100,000. endometriosis was first determined to be a separate condition in the 1920s. before that time, endometriosis and adenomyosis were considered together. it is unclear who first described the disease. signs and symptoms drawing showing endometriosis pain and infertility are common symptoms, although 20–25% of women are asymptomatic. presence of pain symptoms are associated with the type of endometrial lesions as 50% of women with typical lesions, 10% of women with cystic ovarian lesions, and 5% of women with deep endometriosis do not have pain. pelvic pain a major symptom of endometriosis is recurring pelvic pain. the pain can range from mild to severe cramping or stabbing pain that occurs on both sides of the pelvis, in the lower back and rectal area, and even down the legs. the amount of pain a person feels correlates weakly with the extent or stage (1 through 4) of endometriosis, with some individuals having little or no pain despite having extensive endometriosis or endometriosis with scarring, while others may have severe pain even though they have only a few small areas of endometriosis. the most severe pain is typically associated with menstruation. pain can also start a week before a menstrual period, during and even a week after a menstrual period, or it can be constant. the pain can be debilitating and result in emotional stress. symptoms of endometriosis-related pain may include: dysmenorrhea (64%) – painful, sometimes disabling cramps during the menstrual period; 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 or abdominal pain dyspareunia – painful sexual intercourse dysuria – urinary urgency, frequency, and sometimes painful voiding mittelschmerz – pain associated with ovulation bodily movement pain – present during exercise, standing, or walking compared with patients with superficial endometriosis, those with deep disease appear to be more likely to report shooting rectal pain and a sense of their insides being pulled down. individual pain areas and pain intensity appear to be unrelated to the surgical diagnosis, and the area of pain unrelated to the area of endometriosis. there are multiple causes of pain. endometriosis lesions react to hormonal stimulation and may "bleed" at the time of menstruation. the blood accumulates locally if it is not cleared shortly by the immune, circulatory, and lymphatic system. this may further lead to swelling, which triggers inflammation with the activation of cytokines, which results in pain. another source of pain is the organ dislocation that arises from adhesion binding internal organs to each other. the ovaries, the uterus, the oviducts, the peritoneum, and the bladder can be bound together. pain triggered in this way can last throughout the menstrual cycle, not just during menstrual periods. also, endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the central nervous system, potentially producing a variety of individual differences in pain that can, in some cases, become independent of the disease itself. nerve fibres and blood vessels are thought to grow into endometriosis lesions by a process known as neuroangiogenesis. infertility main article: endometriosis and infertility about a third of women with infertility have endometriosis. among those with endometriosis, about 40% are infertile. the pathogenesis of infertility is dependent on the stage of disease: in early stage disease, it is hypothesised that this is secondary to an inflammatory response that impairs various aspects of conception, whereas in later stage disease distorted pelvic anatomy and adhesions contribute to impaired fertilisation. other other symptoms include diarrhea or constipation, chronic fatigue, nausea and vomiting, migraines, low-grade fevers, heavy (44%) and/or irregular periods (60%), and hypoglycemia. there is an association between endometriosis and certain types of cancers, notably some types of ovarian cancer, non-hodgkin's lymphoma and brain cancer. endometriosis is unrelated to endometrial cancer. rarely, endometriosis can cause endometrium-like tissue to be found in other parts of the body. thoracic endometriosis occurs when endometrium-like tissue implants in the lungs or pleura. manifestations of this include coughing up blood, a collapsed lung, or bleeding into the pleural space. endometriosis may also involve the nearby colon which in rare situations may progress to partial obstruction requiring emergency surgery. stress may be a cause or a consequence of endometriosis. physical health complications of endometriosis include internal scarring, adhesions, pelvic cysts, chocolate cysts of ovaries, ruptured cysts, and bowel and ureter obstruction resulting from pelvic adhesions. endometriosis-associated infertility can be related to scar formation and anatomical distortions due to the endometriosis. ovarian endometriosis may complicate pregnancy by decidualization, abscess and/or rupture. thoracic endometriosis can be associated with recurrent thoracic endometriosis syndrome at times of a menstrual period that includes catamenial pneumothorax in 73% of women, catamenial hemothorax in 14%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%. a 20-year study of 12,000 women with endometriosis found that individuals under 40 who are diagnosed with endometriosis are 3 times more likely to have heart problems than their healthy peers. endometriosis may increase about 1% or less chance of getting ovarian, breast and thyroid cancers in women compared with those without. it results in few deaths with unadjusted and age-standardized death rates of 0.1 and 0.0 per 100,000. sciatic endometriosis also called catamenial or cyclical sciatica is a sciatica whose cause is endometriosis and whose incidence is unknown. diagnosis is usually made by an mri or ct-myelography. mental health "endometriosis is associated with an elevated risk of developing depression and anxiety disorders". studies suggest this is partially due to the pelvic pain experienced by endometriosis patients. "it has been demonstrated that pelvic pain has significant negative effects on women's mental health and quality of life; in particular, women who suffer from pelvic pain report high levels of anxiety and depression, loss of working ability, limitations in social activities and a poor quality of life" risk factors genetics endometriosis is a heritable condition that is influenced by both genetic and environmental factors. children or siblings of women with endometriosis are at higher risk of developing endometriosis themselves; low progesterone levels may be genetic, and may contribute to a hormone imbalance. there is an approximate six-fold increased incidence in individuals with an affected first-degree relative. it has been proposed that endometriosis results from a series of multiple hits within target genes, in a mechanism similar to the development of cancer. in this case, the initial mutation may be either somatic or heritable. individual genomic changes (found by genotyping including genome-wide association studies) that have been associated with endometriosis include 9 loci robustly replicated in various mnas reaching genome-wide significance : chromosome gene/cytoband gene product function 1 wnt4/1p36.12 wingless-type mmtv integration site family member 4 vital for development of the female reproductive organs 2 greb1/2p25.1 growth regulation by estrogen in breast cancer 1/fibronectin 1 early response gene in the estrogen regulation pathway/cell adhesion and migration processes 2 etaa1/2p14 (etaa1 activator of atr kinase) is a protein coding gene. diseases associated with etaa1 include adult lymphoma and restless legs syndrome 2 il1a/2q13 interleukin 1 alpha (il-1α) is encoded by the il1a gene. interleukin 1 alpha (il-1α) is encoded by the il1a gene. 4 kdr/4q12 kdr is the human gene encoding kinase insert domain receptor also known as vascular endothelial growth factor receptor 2 (vegfr-2) kdr is the human gene encoding kinase insert domain receptor also known as vascular endothelial growth factor receptor 2 (vegfr-2) 6 id4/6p22.3 inhibitor of dna binding 4 ovarian oncogene, biological function unknown 7 7p15.2 transcription factors influence transcriptional regulation of uterine development 9 cdkn2bas/9p21.3 cyclin-dependent kinase inhibitor 2b antisense rna regulation of tumour suppressor genes 12 vezt/12q22 vezatin, an adherens junction transmembrane protein tumor suppressor gene there are many findings of altered gene expression and epigenetics, but both of these can also be a secondary result of, for example, environmental factors and altered metabolism. examples of altered gene expression include that of mirnas. environmental toxins some factors associated with endometriosis include: prolonged exposure to estrogen; for example, in late menopause or early menarche obstruction of menstrual outflow; for example, in müllerian anomalies several studies have investigated the potential link between exposure to dioxins and endometriosis, but the evidence is equivocal and potential mechanisms are poorly understood. a 2004 review of studies of dioxin and endometriosis concluded that "the human data supporting the dioxin-endometriosis association are scanty and conflicting", and a 2009 follow-up review also found that there was "insufficient evidence" in support of a link between dioxin exposure and developing endometriosis. a 2008 review concluded that more work was needed, stating that "although preliminary work suggests a potential involvement of exposure to dioxins in the pathogenesis of endometriosis, much work remains to clearly define cause and effect and to understand the potential mechanism of toxicity". pathophysiology laparoscopic image of endometriotic lesions at the peritoneum of the pelvic wall 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.