Endometriosis is a disease in which tissue similar to the endometrium—the lining of the uterus (womb)—grows elsewhere in the body. The tissue most often grows close to the uterus, such as on the ovaries, fallopian tubes, or the lining of the pelvis. It can also appear on the bowel, bladder, and in some cases on the lungs or skin. Worldwide, endometriosis affects approximately 10% of the female population of reproductive age, representing nearly 200 million women. Symptoms typically begin in adolescence or the early 20s, and tend to improve after menopause as estrogen levels go down.
Symptoms vary widely between individuals. Some have no symptoms, while for others it is a debilitating disease. Common symptoms include pelvic pain, heavy and painful periods, pain with bowel movements, painful urination, painful sex, fatigue, and infertility. Beyond bodily symptoms, endometriosis can affect a person's mental health and social life. It is not known exactly what causes the disease. Possible causes include backward (retrograde) flow of menstrual fluid, genetic factors, hormones, and problems with the immune system.
A presumed diagnosis can be made based on symptoms and medical imaging; laparoscopy (keyhole surgery) with a biopsy can provide definite confirmation. Other causes of similar symptoms include adenomyosis, uterine fibroids (both of these are conditions that affect the uterus), irritable bowel syndrome, and bladder pain syndrome. On average, it takes 5–12 years from the start of symptoms to receive a diagnosis. Many women report being incorrectly told their symptoms are trivial or normal.
While there is no cure for endometriosis, several treatments can improve symptoms. These include hormonal treatments, pain medication, and surgery. First-line treatments usually consist of hormonal treatment—such as a hormonal IUD (coil) or continuous use of a birth control pill—combined with a non-steroidal anti-inflammatory drug (NSAID) such as naproxen. Other hormonal treatment may be tried if these are not effective. Most individuals benefit from drug treatment, though this approach may lose effectiveness over time. Lesions (patches of endometriosis) may be removed surgically in women whose symptoms are not relieved by other treatments, or when endometriosis is associated with infertility. However, in a substantial minority of such cases, endometriosis returns after surgery.
Subtypes
Endometriosis occurs when endometrium-like tissue grows outside the uterus, forming patches called lesions or implants. It can be classified into three subtypes, or four if extra-pelvic endometriosis is included:
Superficial peritoneal endometriosis Small lesions that grow on the peritoneum, the membrane lining the abdominal cavity and covering the surface of pelvic organs Deep infiltrating endometriosis Lesions that grow into the tissue beneath the lining of the pelvis or into the muscle layers of pelvic organs Endometriomas Cysts that grow in the ovaries Extrapelvic endometriosis Lesions outside the pelvic region, such as in the lungs or diaphragm
Subtypes can exist in isolation or in combination with one another. When lesions grow more than 5 mm beneath the peritoneal surface, they are classified as deep infiltrating endometriosis. Deep endometriosis can infiltrate the muscular layer of organs like the bowel or bladder. It often forms nodules, and can be associated with fibrosis and adhesions. Endometriomas are filled with old menstrual blood among other material and appear dark brown, giving rise to the name "chocolate cysts".
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. Extrapelvic endometriosis—for instance in the lungs or diaphragm (thoracic endometriosis), brain, or skin—is rare. Scar endometriosis can form on the abdominal wall as a complication of surgery, most often following a caesarean section or other pelvic surgery. It forms at or near the location of the surgical cut.
Signs and symptoms Common symptoms of endometriosis include:
Painful periods Chronic pelvic pain Painful sex Painful urination or bowel movements Fatigue Heavy menstrual bleeding Infertility
Some individuals have no symptoms, while others experience severe, life-altering pain. The amount of pain is only weakly related to the anatomical extent of endometriosis. Those with limited endometriosis may have significant pain, while those with severe endometriosis may have few symptoms. Symptoms typically start in adolescence or the early 20s and usually disappear during menopause, as estrogen levels decline. For some, especially women using hormone replacement therapy, symptoms may continue or even appear for the first time during menopause.
Painful symptoms can occur anytime during the menstrual cycle, but are usually more intense during menstruation; in other words, they follow a cyclical pattern. The pain may feel like clawing fingernails or stabbing knives in the lower abdomen, while the period pain specifically can be dull and cramping in nature. The pain may radiate to the lower back. Symptoms can interfere with daily activities, such as school, work, or social activities.
Endometriosis can also involve symptoms like constipation, diarrhea, nausea, bloating, and rectal or abdominal pain. This is sometimes caused by endometriosis on the bowels, but can also be due to concurrent irritable bowel syndrome (IBS). Deep infiltrating endometriosis in the bowel or bladder can cause bowel obstruction and cyclical blood in stool or blood in urine. Premenstrual spotting is also common.
About a quarter of women diagnosed with endometriosis experience infertility. In some women, infertility is the only symptom they experience. The World Health Organization estimates that endometriosis is the ultimate cause of female infertility in 4.8% of cases.
Thoracic endometriosis—endometriosis on the diaphragm, lungs, or pleura (around the lungs)—can cause cyclical cough and cyclical shoulder pain. When present in the lungs, it can cause cyclical blood discharge from the lungs during menstruation. When found in the pleura, it can cause cyclical collapsed lung and bleeding into the pleural space. Most often, the endometriosis is found in the right lung. Endometriosis around scars can be painful and swell during periods. Sciatic endometriosis, which involves the sciatic nerve, causes cyclical nerve pain in the leg.
Concurrent conditions Endometriosis is associated with a higher risk of 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 is almost 50% more likely. Other complications are stillbirth, gestational hypertension, pre-eclampsia, and placental abruption. The rare complication of spontaneous hemoperitoneum in pregnancy, which is highly dangerous to both mother and fetus, is also more common in women with endometriosis.
Beyond its effects in pregnancy, endometriosis is linked to cardiovascular disease, particularly in those who have had the uterus and ovaries removed as treatment for endometriosis. Cohort studies have found associations with strokes, heart attacks (myocardial infarction), high blood pressure, and irregular heartbeat. Depression and anxiety are more common in people with endometriosis compared to healthy people, but occur at the same rate as they do among people with other chronic pain conditions. It is unclear how much this is caused by shared underlying mechanisms, the impact of severe symptoms, stigma, diagnostic delays, or the ineffectiveness of treatment.
Endometriosis often co-occurs with other pain disorders (such as IBS), autoimmune disorders (such as lupus or rheumatoid arthritis), certain cancers, stroke, and long COVID. For instance, a quarter of women with endometriosis have at least one other pain condition. Women with endometriosis have an increased risk of developing ovarian and thyroid cancers, as well as a slightly higher risk of breast cancer.
Risk factors
Genetics Genetics is a significant but not the sole risk factor for endometriosis. Studies attribute half of the risk to genetics; the other half is attributed to environmental factors (like exposures or lifestyle factors). Individuals who have a first-degree relative with endometriosis—such as a parent, sibling, or child—have a three- to nine-fold higher risk of developing the condition. Eighty genetic regions (loci) have been associated with endometriosis. The genes linked to endometriosis 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 some genetic risk factors with migraine, headaches, and neck and back pain, as well as asthma and osteoarthritis.
Reproductive and environmental factors People whose menstrual outflow is obstructed are at greater risk of developing endometriosis. This could for instance be because of an imperforate hymen, a birth defect where the vagina is completely blocked. Another type of obstruction occurs when extra tissue divides the vagina into two sides. This can happen alongside a double uterus. If one side is blocked (an obstructed hemi-vagina), menstrual blood cannot flow out and becomes trapped. 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. Exposure to certain classes of environmental pollutants seems to raise risks. 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. Epidemiological and experimental data suggest that exposure to some of them can increase the risk of endometriosis. Night work and red meat consumption are associated with an increased risk too.
Mechanism
Endometriosis is an inflammatory disease defined by the presence of tissue similar to the lining of the uterus (the endometrium) elsewhere in the body. The endometrium is the tissue that grows over the course of a menstrual cycle and then gets shed with some blood during menstruation. Like the endometrium, endometriosis lesions can shed tissue; however, because this tissue has nowhere to go, it stays close to the lesion.
This trapped tissue, together with the lesions themselves, causes inflammation and can trigger the formation of adhesions, fibrous bands that form between tissues and organs and bind organs together. The lesions can further cause fibrosis, which is excess connective tissue from healing, a form of scarring. Finally, the trapped tissue can form cysts. It is not completely understood how endometriosis causes infertility and pain.
Formation 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 (coelomic metaplasia).