Endometriosis is a condition in which endometrial cells (the cells that form the tissue that lines the uterus [endometrium]) grow in locations outside the uterus. This condition can cause severe pain and damage organs, frequently the reproductive organs.
Endometrial tissue growth is stimulated by the production of hormones throughout a woman’s menstrual cycle. The hormone estrogen causes the lining of the uterus to thicken and develop as it prepares to serve as the source of nutrition for a newly fertilized egg. When pregnancy does not occur, the endometrium is shed and leaves the body during menstruation.
When the endometrial tissue develops outside of the uterus, it grows in response to hormone stimulation as well, but cannot be shed. It attaches to organs, such as the ovaries and fallopian tubes, and can create pain, adhesions and scarring.
Endometriosis usually occurs during a woman’s reproductive years (ages 15 to 44). It is one of the leading causes of female infertility.
The cause of endometriosis is unknown. It is not completely understood if the endometrial tissue moves to other locations from the uterus or develops there as a result of cell changes. Women at higher risk for endometriosis include those who have never given birth, those who have had female surgical procedures and those with menstrual periods that last longer than eight days.
Some women experience chronic pain with endometriosis while others experience little or no discomfort. The most common symptoms of endometriosis include:
Pain during menstruation (dysmenorrhea)
Pain during sexual intercourse (dyspareunia)
Painful urination (dysuria) or painful bowel movements (dyschezia) during menstruation
Heavy menstrual bleeding or any premenstrual bleeding
Endometriosis is typically diagnosed by a gynecologist (GYN) by examination with a laparoscope, a viewing device inserted through an incision in the abdomen. In some cases, a biopsy may be performed of tissue. At the time of the laparoscopy, a physician determines the stage of endometriosis and discusses treatment options with the woman.
Treatment for endometriosis can be medical or surgical, depending on a woman’s age, symptoms and whether or not she plans to become pregnant. Medical treatments affect the hormonal cycles and may limit the growth of endometriosis. They include prescribing birth control pills or other hormones such as progesterone or gonadotrophin releasing hormone (GnRH). Medical treatments cannot reverse any damage caused by endometrial growths. Surgery is the only way to remove the growths.
Conservative surgery attempts to remove only the growths so a woman may still become pregnant. If it is unsuccessful, the physician may need to perform a hysterectomy (surgical removal of the uterus) and remove the ovaries and fallopian tubes. Hysterectomy is considered a treatment of last resort for women in their reproductive years. It is likely to end the symptoms, but also ends the opportunity for pregnancy. Women who have hysterectomies with removal of the ovaries (oophorectomy) reach menopause immediately and may experience related problems (e.g., hot flashes, night sweats, insomnia, osteoporosis). This surgical menopause usually causes more severe symptoms than those from natural menopause.
Even after medical treatments and conservative surgery, many women experience a return of some symptoms and more endometrial growths. It is believed that when a woman reaches menopause, most symptoms gradually lessen and the growths shrink, although studies have not confirmed this theory.
Endometriosis should not be confused with several other diseases of the endometrium, including endometrial cancer and endometritis. Adenomyosis (formerly known as endometriosis interna) is an endometrial condition where the endometrial lining grows deeper into the uterine wall. Formerly classified as a type of endometriosis, adenomyosis is now recognized as a separate and unrelated disease.
About endometriosis
Endometriosis occurs when tissue of the uterine lining (endometrium) grows in areas outside the uterus. Endometrial tissue consists of glands, blood cells and connecting tissue called stromal cells.
During a woman’s monthly cycle, the endometrium responds to changing levels of the hormones estrogen and progesterone. The endometrium thickens to prepare for possible pregnancy. If a woman becomes pregnant, the endometrium provides a place for the fertilized egg to implant in the uterus and develop. If a woman does not become pregnant, the endometrium breaks down and is shed during the menstrual period.
In cases of endometriosis, endometrial tissue grows in other areas of the body. The tissue responds to the woman’s monthly hormonal changes, whether it is in the uterus or located elsewhere. The displaced tissue of endometriosis (called endometrial implants or lesions) grows and expands as it would in the uterus. But it cannot leave the body the way the uterine tissue does during menstruation. As a result, the implants can bleed into other areas or inflame other organs and form scar tissue or adhesions.
Endometrial implants usually occur in the pelvic region, including the:
Ovaries
Fallopian tubes
Peritoneum (the lining of the pelvic cavity)
Outside of the uterus and on its ligaments
Lymph nodes
Many women with endometriosis have lesions in more than one location. Endometriosis sometimes occurs in other parts of the abdomen, such as the rectum and bladder. In rare cases, endometrial tissue is discovered in other body parts such as the arms, legs or lungs.
Endometrial growths begin microscopically small, often as clear lesions. With time, they become larger and darker and can take many shapes. The colors vary, ranging from red, brown or black to clear, white, yellow or pink. The prevailing color may depend on the blood supply, age of the lesion and other nearby tissue. Some endometrial lesions look like other scars or inflammations and may need an experienced physician to recognize them as endometriosis.
The endometrial implants adhere to organs and can affect their function. For example, lesions growing on the ovary or fallopian tube may stick the ovary to the pelvic wall and block the movement of an egg.
More than half of endometriosis cases involve implants that grow within the ovaries, called endometriomas. These endometriomas can fill with blood and other fluids and become darker as they age. The endometriomas are sometimes called endometrial cysts, blood cysts or chocolate cysts for their dark color. They are unrelated to cancers of the ovary.
Endometriosis usually occurs during a woman’s years of menstruation. The condition is very rarely seen before a girl’s first menstrual period (menarche). It is most commonly diagnosed among women in their late 20s, but women may have the condition for years prior to diagnosis.
Many women discover that they have endometriosis only when they seek treatment for infertility. For other women, severe pain causes them to seek treatment. At menopause, the growths can shrink and symptoms lessen in many cases. However, if a menopausal woman uses hormone replacement therapy, which mimics the menstrual hormone cycle, she may continue to experience endometriosis symptoms.
For some women, the pain associated with endometriosis is debilitating and it may worsen over time. The damage to reproductive organs caused by endometriosis is a major cause of infertility among women. It is also largely responsible for hysterectomies and oophorectomies (ovariectomies) performed on premenopausal women. Many women experience recurring symptoms even after extensive medical or surgical treatments for endometriosis.
More than 5.5 million women in the United States have endometriosis, which is about 10 to 15 percent of all women in their reproductive years, according to the National Institutes of Health (NIH). However, the exact incidence of the condition is unknown because women without symptoms or fertility problems may have endometriosis but never seek diagnosis or treatment.
Risk factors and causes of endometriosis
Risk factors are elements that increase a person’s chance of developing a disease or condition. However, not everyone with one or more risk factors will develop the condition. It is also possible that people with no risk factors will develop the condition. Those factors known to increase a woman’s risk of endometriosis include:
Not giving birth (nulliparity). Women who have not given birth and have not had their menstrual cycles interrupted by pregnancy are at greater risk.
Family history. Women with a mother or sister with endometriosis have a higher risk of developing the condition.
Length of menstrual cycle. Women with menstrual cycles shorter than 27 days or whose periods last longer than eight days are at greater risk.
Age. The risk for endometriosis begins with the onset of menstruation and increases with age, until menopause.
Physicians do not know what causes endometriosis. Several theories have been proposed and are still being studied, including:
Retrograde menstruation. In normal menstrual flow, the endometrial tissue breaks up in the uterus and exits through the vagina. Many women experience some retrograde (backward) menstruation, where blood flows in reverse to the fallopian tubes. This misplaced blood and endometrial tissue may be a cause of endometriosis. However, most women normally have some retrograde menstrual flow and do not develop endometriosis.
Blood and lymphatic transportation. Endometrial cells may be transported away from the uterus in the circulatory or lymphatic systems. The cells are deposited at distant sites and develop in response to the hormonal cycles.
Metaplasia. The ability of one type of cell to develop into another type. For example, cells of the peritoneum (pelvic lining) may change into endometrial cells. This change may be stimulated by a malfunction in the immune system or irritation from endometrial tissue that retrograded in menstruation.
Immune system changes. Normally, the immune system should fight endometrial tissue that is located outside the uterus. An impaired immune system may allow endometriosis to develop, either from retrograde menstrual flow or from endometrial implants that develop from other cells.
Environmental causes. Some researchers are studying the effects of certain chemicals such as dioxins as potential causes of endometriosis.
Signs and symptoms of endometriosis
Some common symptoms of endometriosis are:
Pelvic pain, especially during menstruation or just before it begins
Pain during intercourse (dyspareunia)
Painful urination (dysuria) or bowel movements (dyschezia) during menstruation
Unusually heavy menstrual bleeding or any premenstrual bleeding
Infertility
Fatigue
Blood in urine or stool
Chronic pelvic pain or lower back pain
Some women with endometriosis have no symptoms. There is little correlation between symptoms and severity of the condition. Women with no symptoms may have advanced cases that are diagnosed only when they are tested for infertility. Women with relatively minor endometrial implants may experience debilitating pain.
Endometriosis symptoms are shared by other common and unrelated conditions, including irritable bowel syndrome (IBS), ovarian cysts, interstitial cystitis and pelvic inflammatory disease. A woman who experiences any of these symptoms should contact her gynecologist immediately for evaluation.
Diagnosis methods for endometriosis
A physician, often a gynecologist (GYN), will begin by taking a complete medical history and perform a physical examination,including a pelvic examination, to diagnose endometriosis. During the pelvic exam, the GYN may be able to detect masses on the ovaries or uterus. These may be endometrial cysts or implants, or may be related to other conditions. Physicians may also determine that a patient experiences pain when pelvic organs are moved. This can occur when there are a number of adhesions. In some cases, the uterus may become tilted back because of adhesions from the implants. Endometriosis can only be diagnosed by seeing the implants, which requires a surgical procedure, usually laparoscopy.
During this procedure, an incision is made in the abdomen and a small lighted viewing device is inserted into the pelvis. The surgeon can look for endometrial implants and possibly remove them at the same time by excising (cutting) them or burning them off with a laser or cautery (a heating device). Laparoscopy is the more common and less invasive method of diagnosis. An open abdominal surgery called a laparotomy may also diagnose endometriosis, but is less common in the United States. Surgeons can also remove lesions during a diagnostic laparotomy.
After laparoscopy, the physician can determine the stage of endometriosis. A system designed by the American Society for Reproductive Medicine (ASRM) helps classify the severity of the condition. However, the stages may not correspond to a woman’s level of pain. The stages are:
Stage I. Minimal lesions. Isolated superficial implants.
Stage II. Mild lesions. Several small implants and a few adhesions.
Stage III. Moderate lesions. Superficial and deep implants with prominent adhesions.
Stage IV. Severe lesions. Multiple superficial and deep implants, large endometriomas and prominent adhesions.
In addition, imaging tests may be used to rule out conditions that share similar symptoms. These tests can indicate severe cases of endometriosis, but do not provide a definitive diagnosis. For instance, imaging studies (e.g., ultrasound, CAT scan, MRI) of the pelvic region can identify certain endometrial implants or cysts, but not all.
Treatment and prevention for endometriosis
Goals for endometriosis treatment include alleviating pain, minimizing organ damage and preserving a woman’s fertility (if desired). Treatment is very individualized and depends on a woman’s age, the severity of her symptoms and her plans for future pregnancy. Pain is the most common reason women seek treatment for endometriosis.
Women with mild or no symptoms who do not want to become pregnant may choose no treatment. Women who want children may be encouraged to try to become pregnant sooner rather than later because the negative effects of endometriosis on infertility may increase with age. In addition, it was formerly thought that pregnancy can reduce the condition’s symptoms. However, recent studies indicate that pregnancy does not alleviate symptoms and symptoms may return after pregnancy for many women.
Studies have not proven the best method for treating pelvic pain, but medical treatment options for endometriosis include:
Pain medication (analgesics). Over-the-counter anti-inflammatory medications can provide relief for mild to moderate pain. However, they cannot change or remove any endometrial implants. Physicians may prescribe narcotic painkillers for severe endometriosis pain. These medications are used to alleviate symptoms, but do not have an impact on the underlying condition.
Birth control pills. Endometrial lesions respond to hormones, including the estrogen and progestin usually found in birth control pills or patches. Therefore, these medications may lessen the severity of symptoms. Symptoms may return when a woman stops taking the medication because it does not have an impact on the underlying condition (scarring and adhesions). Birth control pills may have side effects, including nausea and mild weight gain.
Other hormonal treatments. Hormone therapy can produce the same effects as menopause or pregnancy. The goal is to stop menstruation, which can take several months. Hormonal treatments may minimize endometrial symptoms and shrink implants, but will not affect any scarring or adhesions that have already formed. They are rarely effective in women with severe endometriosis. Hormonal treatments include:
Progesterone. A synthetic form of progestin that may be taken as pills or injections. It may control symptoms by reducing or stopping menstruation and stopping ovulation. Side effects include weight gain and mood changes. Progesterone is administered as a daily pill or in periodic shots. Progesterone may not be recommended for a woman who wants to become pregnant. Return of ovulation may be delayed after progesterone therapy has stopped. Ovulation may take up to a year to return after progesterone injections.
GnRH agonists. These are synthetic drugs similar to the natural gonadotrophin releasing hormone (GnRH), which induce a chemical menopause. They are administered as a nasal spray or an injection. GnRH agonists are usually prescribed for only six months because they increase the risk of bone loss that may lead to osteoporosis. Side effects are similar to symptoms of menopause, including hot flashes, vaginal dryness, loss of bone density and insomnia. Most women with severe cases of endometriosis who are treated with GnRH agonists will experience recurrent pain after discontinuing use.
Synthetic androgens. Medications (such as danazol) that are similar to male hormones (androgens) affect the production of female hormones and stop menstruation. These hormones are taken as pills for six to nine months. Some side effects include acne, weight gain and hirsutism (growth of facial or body hair). Some of these side effects may not reverse after the medication is discontinued. Androgens should not be taken by women with certain types of liver, kidney or heart disease because it can worsen those conditions.
All these hormonal treatments can affect an embryo and women must take steps to avoid pregnancy during the treatments. Because birth control pills may not be used in combination with the other hormonal treatments, a woman should use another method of contraception (e.g., condoms) with any of these treatments. When the treatments are complete and menstruation returns, a woman may attempt to become pregnant. Patients may experience a recurrence of endometriosis symptoms after hormonal treatments stop.
Physicians consider surgery for endometriosis when there are advanced adhesions and scarring or when medical therapy has not alleviated symptoms, such as severe pain. There are several surgical options for endometriosis:
Conservative surgery. Involves removing the endometrial implants while maintaining the reproductive organs. This is the preferred surgical treatment for endometriosis. The patient is sedated with anesthesia and a surgeon performs a laparoscopy or laparotomy to remove the implants by heat, laser or excision (cutting them out). Excision is the preferred method because it allows the lesions to be examined in a biopsy. Surgeons can also correct the position of any organs (e.g., ovaries) that may have become displaced because of the adhesions.
Adhesions around the organs can be cut, and at times blocked fallopian tubes can be repaired. These procedures may involve removing one ovary, but no other organs, so a woman may still be able to have children. Many women are able to become pregnant after conservative surgery, depending on the severity of the endometriosis before the surgery. Damage to the inside of the fallopian tube from endometriosis can result in a woman requiring in vitro fertilization (IVF) to become pregnant. Symptoms may still recur after surgery and some women have repeated laparoscopies or laparotomies.
Laparoscopic uterosacral nerve ablation (LUNA). This procedure involves cutting a nerve between the uterus and the ligaments that hold it in place. It may help women with a specific type of pain, but studies show that many women experience no pain relief. Any severing of nerves is permanent and cannot be reversed.
Hysterectomy. This procedure removes a woman’s uterus. For endometriosis, surgeons also remove the ovaries and fallopian tubes (bilateral salpingo-oophorectomy) and any implants or adhesions. Hysterectomy usually ends the endometriosis symptoms, but also ends the possibility of childbearing. It is considered a treatment of last resort. After removal of the ovaries, a woman begins menopause because her body no longer produces estrogen. Although the surgery may alleviate the endometriosis symptoms, the surgical menopause will create other symptoms such as hot flashes, weight gain and vaginal dryness. Surgical menopause caused by hysterectomy may cause more severe symptoms than those from natural menopause. After a hysterectomy, a woman will usually be prescribed estrogen replacement therapy.
With all endometriosis treatments, the condition may recur and the pain may return, although it is uncommon after hysterectomy. Some women are able to get pregnant naturally after conservative surgical treatment for endometriosis. Others are able to become pregnant using assisted reproductive technology (ART). An obstetrician can best discuss fertility options with a patient and her partner.
There is no cure for endometriosis. A woman may consult with her physician to determine the best course of treatment for the disease, its symptoms and her fertility. Cost of treatment may be a consideration. Some hormone therapies such as GnRH agonists are extremely expensive, as are repeated surgeries.
There are no known methods to prevent endometriosis. The disease usually continues unless it is interrupted by pregnancy or treated with some form of therapy. It can recur with all treatments, though some are more effective than others. At menopause, the symptoms may lessen in many women. The effect of hormone replacement therapy in women with endometriosis who reach natural menopause is unknown.
In addition, the herbal supplement Pycnogenol – a plant extract from the bark of the French maritime pine tree – may significantly reduce pain symptoms (e.g., pelvic pain, dysmenorrhea) in endometriosis patients, according to a new study. Pycnogenol is commercially available in numerous health food stores and other nutrition venues. However, health experts recommend caution when using herbal supplements since sufficient studies have not been conducted to determine their long-term safety or efficacy for treating any health condition. Patients are urged to consult a physician before taking any herbs or nutritional supplements.
Ongoing research regarding endometriosis
Lack of agreement about the causes of endometriosis leaves a wide range of areas for research. Scientists continue to investigate the cause of the condition and potential areas of improved diagnosis and treatment. Some subjects of ongoing research include:
Hormone-related therapy. Many of the studies for endometriosis treatment involve hormones, hormonal receptors and drugs that affect hormones. Some of these include:
Selective estrogen receptor modulators (SERMs). These drugs act like estrogen in some tissues but like estrogen blockers in others. Animal studies involving specific SERMs have shown decreased lesion size. However, tamoxifen, a SERM used in breast cancer patients, may worsen endometriosis. Drugs that block progesterone in a similar manner (selective progesterone receptor modifiers, or SPRMs) are also being developed and studied.
Gonadotrophin releasing hormone (GnRH) antagonists. These drugs are designed to be more effective against endometriosis symptoms than GnRH agonists, without many of the side effects.
Aromatase inhibitors. Aromatase is an enzyme that helps produce estrogen in postmenopausal women. Some women with endometriosis have abnormal aromatase levels. One study of an aromatase inhibitor showed successful treatment of endometriosis in postmenopausal women. Clinical trials are being conducted among younger women. Aromatase inhibitors cause bone loss, which complicates their use.
Mifepristone (RU-486). Some researchers are studying the use of this antiprogestin drug, which affects both progesterone and estrogen. It has been shown to block the effects of natural progesterone and improves endometriosis symptoms and reduces implants. The drug is licensed in the United States to induce abortions by causing a miscarriage. Some other antiprogestins are also being studied.
Photodynamic therapy. Trials using this therapy involve intravenous (into a vein) injection of a dye concentrated in areas of endometriosis. A laser produces a photochemical reaction to destroy the lesions.
Immune system. Some women with endometriosis have other conditions related to impaired immune function, such as lupus. Certain types of immune cells may be impaired in women with endometriosis. Some studies are under way about the immune response to endometriosis.
Endometriosis markers. Researchers are investigating substances that could indicate the presence of endometriosis through a blood test or urine test. This would enable physicians to diagnose the condition without surgery.
Guidelines. A study group of researchers, clinicians and patient representatives based in the European Society of Human Reproduction and Embryology (ESHRE) is devising guidelines for the diagnosis and treatment of endometriosis.
Questions for your doctor about endometriosis
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor or healthcare professional the following questions regarding endometriosis:
What tests are needed to confirm I have endometriosis?
How will I need to prepare for those tests?
What is the stage of my endometriosis?
What are my treatment options for this condition?
What are the risks associated with these treatments?
What medications are best to help with my pain?
How will this condition affect my fertility?
When should I begin to be concerned about my ability to become pregnant?
Should my female relatives be screened for endometriosis because I have the condition?
How many patients with endometriosis have you treated?
Can my surgery spare my uterus and ovaries?
Will you be able to perform a biopsy of the tissue?
Are you experienced with laparoscopy and laparotomy for endometriosis?
What is the chance my endometriosis will return after treatment?
