Endometriosis

ANATOMY OR SYSTEM AFFECTED: Reproductive system, uterus

DEFINITION: Growth of cells of the uterine lining at sites outside the uterus, causing severe pain and infertility.

CAUSES: Unknown

SYMPTOMS: Painful menstrual periods, discomfort during sexual intercourse, localized pain, infertility

DURATION: Chronic

TREATMENTS: Chemotherapy, surgery

Causes and Symptoms

Endometriosis is the presence of endometrial tissue outside its normal location as the lining of the . It can be asymptomatic, mild, or a disabling disease causing severe pain. The classic symptoms of endometriosis are very painful (dysmenorrhea), painful intercourse (dyspareunia), and infertility. Some other common endometriosis symptoms include pain in the abdomen, lower back, or pelvis, premenstrual pain, and pain when passing stool. Many women who have endometriosis do not experience any symptoms, however.

In 2023, the World Health Organization estimated that endometriosis affected about 10 percent of women of childbearing age across the globe. Often, it is incorrectly stereotyped as being a disease of upwardly mobile, professional women. According to many experts, the incidence of endometriosis worldwide and across most racial groups is probably very similar. They propose that the reported occurrence rate difference for some racial groups, such as a lower incidence in African Americans and a higher diagnosis rate among Caucasians, has been a socioeconomic phenomenon attributable to the social class of women who seek medical treatment for the symptoms of endometriosis and to the highly stratified responses of many health care professionals who have dealt with the disease. Likely risk factors include having a family history of endometriosis, early onset of menstruation, a menstrual cycle shorter than twenty-eight days, menstrual periods of longer than six days, low birth weight, abnormalities in the reproductive tract, and no or widely spaced pregnancies.

The symptoms of endometriosis arise from abnormalities in the effects of the menstrual cycle on the endometrial tissue lining the uterus. The endometrium normally thickens and becomes engorged (swollen with blood) during the cycle, a process controlled by female hormones called "estrogens" and "progestins." This engorgement is designed to prepare the uterus for by optimizing conditions for implantation in the endometrium of a fertilized egg, which enters the uterus via one of the Fallopian tubes leading from the ovaries.

By the middle of the menstrual cycle, the endometrial lining is normally about ten times thicker than at its beginning. If the egg that is released into the uterus is not fertilized, does not occur and decreases in production of the female sex hormones result in the breakdown of the endometrium. Endometrial tissue mixed with blood leaves the uterus as the menstrual flow, and a new menstrual cycle begins. This series of uterine changes occurs repeatedly, as a monthly cycle, from (which usually occurs between the ages of twelve and fourteen) to menopause (which usually occurs between the ages of forty-five and fifty-five).

In women who develop endometriosis, some endometrial tissue begins to grow ectopically (in an abnormal position) at sites outside the uterus. The ectopic endometrial growths may be found attached to the ovaries, the Fallopian tubes, the urinary bladder, the rectum, other abdominal organs, and even the lungs. Regardless of body location, these implants behave as if they were still in the uterus, thickening and bleeding each month as the menstrual cycle proceeds. Like the endometrium at its normal uterine site, the ectopic tissue responds to the hormones that circulate through the body in the blood. Its inappropriate position in the body prevents this ectopic endometrial tissue from leaving the body as menstrual flow; as a result, some implants grow to be quite large.

In many cases, the endometrial growths that form between two organs become fibrous bands called "adhesions." The fibrous nature of adhesions is attributable to the alternating swelling and breakdown of the ectopic tissue, which yields fibrous scar tissue. The alterations in size of living portions of the adhesions and other endometrial implants during the monthly menstrual cycle cause many afflicted women considerable pain. Because the body location of implants varies, the site of the pain may be almost anywhere, including the back, chest, thighs, pelvis, rectum, or abdomen. For example, occurs when adhesions hold a uterus tightly to the abdominal wall, making its movement during intercourse painful. Many women report significant pain on a monthly basis with as well.

The presence of endometriosis is usually confirmed by an imaging test, such as ultrasound or magnetic resonance imaging (MRI), and laparoscopy, viewed as being the most reliable method for its diagnosis. During a transvaginal ultrasound, a transducer is inserted through the patient's vagina, allowing the reproductive organs to be visualized and adhesion to the bowel structures to be detected. Laparoscopy is carried out after a physician makes an initial diagnosis of probable endometriosis from a combined study including an examination of the patient’s medical history and careful exploration of the patient’s physical problems over a period of at least six months. During prelaparoscopy treatment, the patient is very often maintained on pain medication and other therapeutic drugs that will produce symptomatic relief.

For laparoscopy, the patient is anesthetized with a general anesthetic, a small incision is made near the navel, and a laparoscope (flexible lighted tube) is inserted into this incision. The laparoscope, equipped with fiber optics, enables the examining physician to search the patient’s abdominal organs for endometrial implants. Visibility of the abdominal organs in laparoscopic examination can be enhanced by pumping harmless gas into the abdomen, causing it to distend. Women who undergo usually require a day of bed rest, followed by seven to ten days of curtailed physical activity. A biopsy may be done to determine whether any lesions found are malignant. After a positive diagnosis of endometriosis is made, a variety of surgical and therapeutic drug treatments can be employed to manage the disease.

Between 30 and 50 percent of all women who have endometriosis are infertile; contemporary wisdom evaluates this relationship as one of cause and effect, which should make this disease the second most common cause of fertility problems. The actual basis for this infertility is not always clear, but it is often the result of damage to the and Fallopian tubes, scar tissue produced by implants on these and other abdominal organs, and hormone imbalances.

Because the incidence of infertility accompanying endometriosis increases with the severity of the disease, all potentially afflicted women are encouraged to seek early diagnosis. Many experts advise all women with abnormal menstrual cycles, dysmenorrhea, severe menstrual bleeding, abnormal vaginal bleeding, and repeated dyspareunia to seek the advice of a physician trained in identifying and dealing with endometriosis. Because the disease can begin to present symptoms at any age, teenagers are also encouraged to seek medical attention if they experience any of these symptoms.

John Sampson coined the term “endometriosis” in the 1920s. Sampson’s theory for its causation, still widely accepted, is termed "retrograde menstruation." Also called "menstrual backup," this theory proposes that the backing up of some menstrual flow into the Fallopian tubes and then into the abdominal cavity, forms the endometrial implants. Evidence supporting this theory, according to many physicians, is the fact that such backup is common. Others point out, however, that the backup is often found in women who do not have the disease. A surgical experiment was performed on female monkeys to test this theory. Their uteri were turned upside down so that the menstrual flow would spill into the abdominal cavity. Sixty percent of the animals developed endometriosis postoperatively—an inconclusive result.

Complicating the issue is the fact that implants are also found in tissues (such as in the lung) that cannot be reached by menstrual backup. It has been theorized that the presence of these implants results from the entry of endometrial cells into the lymphatic system, which returns body to the blood and protects the body from many other diseases. This theory is supported by the occurrence of endometriosis in various portions of the and in tissues that could not otherwise become sites of endometriosis.

A third theory explaining the growth of implants is the iatrogenic, or nosocomial, of endometrial tissue. These terms both indicate an accidental creation of the disease through the actions of physicians. Such implant formation is viewed as occurring most often after cesarean delivery of a baby when passage through the birth canal would otherwise be fatal to mother and/or child. Another proposed cause is episiotomy—widening of the birth canal by an incision between the anus and vagina—to ease births.

Any surgical procedure that allows the spread of endometrial tissue can be implicated, including surgical procedures carried out to correct existing endometriosis, because of the ease with which endometrial tissue implants itself anywhere in the body. Abnormal endometrial tissue growth, called "adenomyosis," can also occur in the uterus and is viewed as a separate disease entity.

Other theories regarding the genesis of endometriosis include an immunologic theory, which proposes that women who develop endometriosis are lacking in antibodies that normally cause the destruction of endometrial tissue at sites where it does not belong, and a hormonal theory, which suggests the existence of large imbalances in hormones such as the that serve as the body’s messengers in controlling biological processes. Several of these theories—retrograde menstruation, the transplantation theory, and transmission—all have support, but none has been proved unequivocally. Future evidence will identify whether one cause is dominant, whether they all interact to produce the disease, or whether endometriosis is actually a group of diseases that simply resemble one another in the eyes of contemporary medical science.

Treatment and Therapy

Laparoscopic examination most often identifies endometriosis as chocolate-colored lumps (chocolate cysts) ranging from the size of a pinhead to several inches across or as filmy coverings over parts of abdominal organs and ligaments. Once a diagnosis of the disease is confirmed by laparoscopy, endometriosis is treated by chemotherapy (medication), surgery, or a combination of both methods. The only permanent contemporary cure for endometriosis, however, is the onset of the biological menopause at the end of a woman’s childbearing years. As long as menstruation continues, implant development is likely to recur, regardless of its cause. Nevertheless, a temporary cure of endometriosis is better than no cure at all.

The that many physicians use to treat mild cases of endometriosis (and for prelaparoscopy periods) is painkillers, including aspirin, acetaminophen, and ibuprofen. The analgesics inhibit the body’s production of prostaglandins, and the symptoms of the disease are merely covered up. Therefore, analgesics are of quite limited value except during a prelaparoscopy diagnostic period or with mild cases of endometriosis. In addition, the long-term administration of aspirin will often produce bleeding, and excess use of acetaminophen can lead to severe liver damage. In some cases of very severe endometriosis pain, narcotic painkillers are given, such as codeine, Percodan (oxycodone and aspirin), or morphine. Narcotics are addicting and should be avoided unless absolutely necessary.

More effective for long-term management of the disease is hormone therapy. Such therapy is designed to prevent the monthly occurrence of menstruation—that is, to freeze the body in a sort of chemical menopause. The hormone types used, made by companies, are chemical cousins of female hormones (estrogens and progestins), male hormones (androgens), and a hormone that controls ovulation (gonadotropin-releasing hormone, or GnRH). Appropriate is often useful for years, although each hormone class produces disadvantageous side effects in many patients.

The use of estrogens stops ovulation and menstruation, freeing many women with endometriosis from painful symptoms. Numerous preparations have been prescribed, including the birth control pills that contain them. Drawbacks of estrogen use can include weight gain, nausea, breast soreness, depression, blood-clotting abnormalities, and elevated risk of vaginal cancer. In addition, estrogen administration may cause endometrial implants to enlarge.

The use of progestins arose from the discovery that pregnancy—which is maintained by high levels of a natural progestin called progesterone—reversed the symptoms of many suffering from endometriosis. This realization led to the utilization of synthetic progestins to cause prolonged false pregnancy. The rationale is that all endometrial implants will die off and be reabsorbed during the prolonged absence of menstruation. The method works in most patients, and pain-free periods of up to five years are often observed. In some cases, however, side effects include nausea, depression, insomnia, and a very slow resumption of normal menstruation (such as lags of up to a year) when the therapy is stopped. In addition, progestins are ineffective in treating large implants; in fact, their use in such cases can lead to severe complications.

In the 1970s, studies showing the potential for heart attacks, high blood pressure, and strokes in patients receiving long-term female hormone therapy led to a search for more advantageous hormone medications. An alternative developed was the synthetic male hormone danazol (Danocrine), which is very effective. Danazol works by decreasing the amount of estrogen that is produced by the ovaries on a monthly basis to close to that which is present at menopause. The lack of estrogen prevents endometrial cells from growing, thereby eliminating most of the symptoms associated with endometriosis. One of its advantages over female hormones is the ability to shrink large implants and restore fertility to those patients whose problems arise from nonfunctional ovaries or Fallopian tubes. Danazol has become the drug of choice for treating millions of endometriosis sufferers. Problems associated with danazol use, however, can include weight gain, masculinization (decreased bust size, increased muscle mass, muscle cramping, facial growth, and deepened voice), fatigue, depression, and baldness. Those women contemplating danazol use should be aware that it can also complicate pregnancy.

Because of the side effects of these hormones, other chemotherapy was sought. Another valuable drug that has become available is gonadotropin-releasing hormone (GnRH), which suppresses the function of the ovaries in a fashion equivalent to surgical (removal of the ovaries). This hormone produces none of the side effects of the sex hormones, such as weight gain, depression, or masculinization, but some evidence indicates that it may lead to osteoporosis.

Thus, despite the fact that hormone therapy may relieve or reduce pain for years, contemporary chemotherapy is flawed by many undesirable side effects. Perhaps more serious, however, is the high rate of endometriosis that is observed after the therapy is stopped. Consequently, it appears that the best treatment of endometriosis combines chemotherapy with surgery.

The extent of the surgery carried out to combat endometriosis is and depends on the observations made during laparoscopy. In cases of relatively mild endometriosis, conservative surgery removes endometriosis implants, adhesions, and lesions. This type of procedure attempts to relieve endometriosis pain, to minimize the chances of postoperative recurrence of the disease, and to allow the patient to have children. Even in the most severe cases of this type, the uterus, an ovary, and its associated Fallopian tube are retained. Such surgery will often include removal of the appendix, whether diseased or not, because it is very likely to develop implants. The surgical techniques performed are the conventional excision of diseased tissue or the use of lasers to vaporize it. Many physicians prefer lasers because it is believed that they decrease the chances of recurrent endometriosis resulting from retained implant tissue or iatrogenic causes. In a new procedure, following the removal of endometrial tissue by surgical means, an intrauterine device containing levonogestrel (a hormone that will decrease estrogen levels) is placed in order to prevent recurrence of endometriosis.

In more serious cases, is carried out. All visible implants, adhesions, and lesions are removed from the abdominal organs, as in conservative surgery. In addition, the uterus and are taken out, but one or both ovaries are retained. This allows female hormone production to continue normally until the menopause. Uterine removal makes it impossible to have children, however, and may lead to profound psychological problems that require psychiatric help. Women planning to elect for hysterectomy to treat endometriosis should be aware of such potential difficulties. In many cases of conservative surgery or hysterectomy, danazol is used, both preoperatively and postoperatively, to minimize implant size.

The most extensive surgery carried out on the women afflicted with endometriosis is radical hysterectomy, also called "definitive surgery," in which the ovaries and/or the are also removed. The resultant symptoms are menopausal and may include vaginal bleeding (when the vagina is retained), increased risk of heart disease, and the development of osteoporosis. To counter the occurrence of these symptoms, hormone replacement therapy is suggested. Paradoxically, this hormone therapy can lead to the return of endometriosis by stimulating the growth of residual implant tissue.

Recently, more women have turned to complementary and alternative medicine in an attempt to relieve the symptoms of endometriosis. Acupuncture, homeopathy, and herbal therapy are being explored as means of treatment for endometriosis.

Perspective and Prospects

Modern treatment of endometriosis is viewed by many physicians as beginning in the 1950s. A landmark development in this field was the accurate diagnosis of endometriosis via the laparoscope, which was invented in Europe and introduced into the United States in the 1960s. Medical science has progressed greatly since that time. Physicians and researchers have recognized the wide occurrence of the disease and accepted its symptoms as valid; realized that hysterectomy will not necessarily put an end to the disease; utilized chemotherapeutic tools, including hormones and painkillers, as treatments and as adjuncts to surgery; developed laser surgery and other techniques that decrease the occurrence of formerly ignored iatrogenic endometriosis; and understood that the disease can ravage teenagers as well and that these young women should be examined as early as possible.

Research into endometriosis is ongoing, and the efforts and information base of the proactive American Endometriosis Association, founded in 1980, have been very valuable. As a result, a potentially or presently afflicted woman is much more aware of the problems associated with the disease. In addition, she has a source for obtaining objective information on topics including state-of-the-art treatment, physician and hospital choice, and both physical and psychological outcomes of treatment.

Many potentially viable avenues for better endometriosis diagnosis and treatment have become the objects of intense investigation. These include the use of and techniques, such as magnetic resonance imaging (MRI), for the predictive, nonsurgical examination of the course of growth or the chemotherapeutic destruction of implants; the design of new drugs to be utilized in the battle against endometriosis; endeavors aimed at the development of diagnostic tests for the disease that will stop it before symptoms develop; and the design of dietary treatments to soften its effects.

Regrettably, because of the insidious nature of endometriosis—which has the ability to strike almost anywhere in the body—some confusion about the disease still exists. New drugs, surgical techniques, and other aids are expected to be helpful in clarifying many of these issues. Particular value is being placed on the study of the immunologic aspects of endometriosis. Scientists hope to explain why the disease strikes some women and not others, to uncover its etiologic basis, and to solve the widespread problems of iatrogenic implant formation and other types of endometriosis recurrence.

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