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  • When the normal lining of the uterus starts to grow outside the uterine wall
  • Symptoms include pelvic pain, painful periods, pain with sexual intercourse, heavy periods, infertility
  • Treatment includes medication, surgery
  • Involves Endometriosis Program, Obstetrics, Gynecology & Reproductive Sciences, Minimally Invasive Surgical Program
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Endometriosis occurs when tissue similar to that found in the endometrium—the lining of the uterus—grows outside the uterus. Among other symptoms, it can cause chronic pelvic pain, painful periods, pain during or after sexual intercourse, and infertility.

Endometriosis has traditionally been thought of as a disorder that primarily affects the pelvic area; however, it is now recognized as a systemic disorder, meaning its effects occur throughout the body. In addition to pelvic symptoms, research shows that women with endometriosis have higher rates of depression and anxiety than those who do not have the condition, often experience fatigue, and are at increased risk for developing cardiovascular disease.

Endometriosis is a common condition. It affects an estimated 5%-10% of women and adolescents of reproductive age (15-49 years) and up to 50% of women who are infertile. Between 50% and 80% of women with pelvic pain have endometriosis. The condition often goes undiagnosed or misdiagnosed for years, partly because its symptoms can vary greatly and may be caused by other conditions. Also, a definitive diagnosis requires surgery, which is invasive and, in rare cases, can cause significant complications. On average, there is a four-to-11-year delay between the onset of symptoms and diagnosis (and treatment).

While there is no cure for endometriosis, a number of treatment options are available, including medications and surgery, that can help manage symptoms, slow the progression of the condition, increase a woman’s chances of getting pregnant, and improve quality of life.

"We are at the forefront of diagnosing and treating this disease, from which many women suffer in silence for years," says Yale Medicine's Hugh Taylor, MD, chair of the Department of Obstetrics, Gynecology & Reproductive Sciences.

What is endometriosis?

Endometriosis is a chronic, inflammatory disease that can cause debilitating pelvic and period pain, as well as infertility. It also affects parts of the body beyond the pelvic area.

The uterus, or womb, is lined with a layer of tissue called the endometrium. During the menstrual cycle, hormones, including estrogen (which is produced by the ovaries), cause the endometrium to thicken, in preparation for supporting a fertilized egg. If an egg is not fertilized, the endometrium breaks down, and during a menstrual period, blood and endometrial tissue are shed from the uterus through the vagina.

In someone with endometriosis, endometrial-like tissue grows outside the uterus. These growths may be referred to as implants, lesions, or nodules. The tissue may grow in the ovaries, fallopian tubes, large intestine, rectum, and bladder. In rare cases, it can also grow elsewhere in the body, such as in the lungs, vulva, brain, and pericardium (the tissue membrane that surrounds the heart).

Endometrial tissue that grows outside the uterus responds to the hormones involved in the menstrual cycle. In particular, the hormone estrogen plays an important role, and endometriosis is often described as an “estrogen-dependent condition.” Estrogen can cause endometrial tissue to grow and bleed, including implants located outside the uterus. This can lead to inflammation, the formation of scar tissue, and adhesions that can join organs to one another.

The implants and inflammation can cause pain (which may increase before and during periods) and heavy periods. The inflammation may also damage eggs and sperm, and implants can block the egg from moving through the fallopian tube and uterus, causing infertility.

Many treatments for the condition work by lowering estrogen levels, which helps shrink endometrial implants and reduce symptoms.

The effects of endometriosis, such as inflammation, can also occur throughout the body. Research suggests that this may be due to changes in the way cells in the immune system function, as well as increased production of proteins (known as cytokines) that trigger inflammation.

Research has also shown that microRNAs, molecules that help regulate the way genes are expressed in organs around the body, are altered in women with endometriosis, and may contribute to inflammation. Women with endometriosis are also at increased risk for cardiovascular disease. This is because the widespread inflammation caused by endometriosis increases risk for developing atherosclerosis and coronary artery disease.

Endometriosis is also associated with mood disorders, in particular depression and anxiety. These disorders arise due to changes in the gene expressions in parts of the brain that are believed to be involved in depression and anxiety. Being underweight is also associated with endometriosis. This may be the result of changes in gene expression in other parts of the body that alter the metabolism of women with endometriosis.

What causes endometriosis?

The cause of endometriosis is unknown, though the condition likely develops due to multiple factors.

Researchers and doctors have proposed a number of theories about the cause of endometriosis, the most common of which is known as the retrograde menstruation theory.

This theory contends that some menstrual blood and pieces of endometrium that are normally shed through the vagina flow backward (or retrograde) into the fallopian tubes and the pelvis. The endometrial cells then attach to and grow on tissues in the pelvis.

However, it’s important to note that the majority of women experience retrograde menstruation, though most do not have endometriosis. Also, endometrial implants sometimes occur in the lung or other areas outside the pelvis, which are not explained by the retrograde menstruation theory.

Another theory holds that stem cells play a role in endometriosis. Stem cells are involved in regenerating the endometrium after it is shed during menstruation. In this theory, stem cells that can develop into endometrial cells (the kind of cells that make up the endometrium) circulate beyond the pelvis and give rise to endometrial implants.

Other factors may also play a role, including:

  • Genetics. There is evidence that people with first-degree relatives (i.e., mothers or sisters) with endometriosis are more likely to develop the condition, suggesting that genetics may be a factor.
  • Altered immune system function. Normally, the immune system clears away endometrial tissue found outside the uterus. In people with endometriosis, however, the immune system may not effectively remove this tissue. ­­

What are the risk factors for endometriosis?

Certain factors may increase the risk of developing endometriosis, including:

  • Family history of first-degree relatives with endometriosis
  • Never having given birth
  • Starting menstruation early (before age 11)
  • Short menstrual cycles (27 or fewer days)
  • Heavy menstrual periods that last longer than seven days
  • Late menopause
  • Menstrual flow obstruction caused by structural abnormalities in the uterus, such as cervical stenosis (narrowing of the cervix)

Some factors are associated with a lower risk of developing endometriosis, including:

  • Giving birth multiple times
  • Starting menstruation late (after age 14)
  • Prolonged breastfeeding

What are the symptoms of endometriosis?

Up to 30% of women with endometriosis do not have any symptoms. When symptoms occur, they can range from mild to severe.

Endometriosis symptoms that affect the pelvic area may include:

  • Chronic pelvic pain (pain in the pelvic area, lower abdomen, or lower back that lasts six or more months)
  • Painful periods (pain may begin before and occur during menstruation and may worsen over time)
  • Pain during or after sexual intercourse (pain may be worse during periods)
  • Heavy or prolonged menstrual bleeding
  • Inability to get pregnant
  • Painful or uncomfortable urination
  • Pain during bowel movements
  • Spotting or bleeding between periods

Women with endometriosis can also develop endometriomas—fluid-filled cysts in the ovaries that form from endometrial tissue. They can cause pelvic pain and can rupture, causing abdominal pain.

Other symptoms include:

  • Depression and anxiety
  • Being underweight (having a low body mass index, or BMI)
  • Fatigue
  • Hypersensitivity to pain (known as central pain sensitization)

How is endometriosis diagnosed?

To diagnose endometriosis, your doctor will assess your medical history, perform a pelvic exam, and run diagnostic tests.

Diagnosis often begins with a review of your medical history. Your doctor will ask about your symptoms, whether you have any risk factors associated with endometriosis, and whether you are having difficulty getting pregnant. They may also ask about your periods, such as whether you have painful periods, the average time between periods, the length of your periods, and whether pelvic pain worsens during periods.

Your doctor will also conduct a physical exam that includes a pelvic exam. During the pelvic exam, the doctor will check for any signs of endometriosis, such as tenderness or pain, or, in some cases, a palpable lump near the ovaries.

After reviewing your medical history and performing a physical exam, your doctor may order imaging tests, including an ultrasound, transvaginal ultrasound, and/or magnetic resonance imaging (MRI), to visually examine tissues in the pelvic area. These imaging tests can help doctors identify endometrial implants in the bowel, bladder, or other tissues.

At this point, your doctor may make what is called a “clinical diagnosis” based on your medical history, findings during the physical exam, and imaging results. While this is not a definitive diagnosis, a clinical diagnosis allows you to begin treatment immediately, without undergoing an invasive surgical diagnostic procedure. After getting a clinical diagnosis, you may be prescribed medications, such as hormonal contraceptives or pain medications, to avoid treatment delays.

Sometimes, a definitive diagnosis of endometriosis will require a surgical procedure. Diagnostic surgery is typically done using laparoscopy, a minimally invasive technique in which a surgeon makes a small incision in the abdomen, usually near the belly button. The surgeon inserts a laparoscope—a long, thin tube equipped with a light and camera—through the incision and into the abdominal cavity and inflates the cavity with carbon dioxide gas.

Then, using the laparoscope, the surgeon examines the abdominal cavity to visually identify and examine any endometrial implants. During the procedure, the surgeon can biopsy endometrial implants and abnormal tissues to send for laboratory analysis to confirm a diagnosis.

If endometrial tissue is identified during the diagnostic procedure, the surgeon may treat it by removing or destroying it.

After surgical diagnosis, the doctor will classify the condition based on the location and amount of endometrial tissue that occurs in abnormal locations, how deep the tissue is in other organs (for instance—on the surface or deep), and other factors. Different staging systems may be used. In the American Society for Reproductive Medicine (ASRM) system, there are four stages: Stage I (minimal), stage II (mild), stage III (moderate), and stage IV (severe). However, these stages do not correlate well with symptoms or infertility. This means that symptoms may range from mild to severe—or may even be absent—at any of the four stages. Determining the stage of endometriosis helps doctors standardize their evaluation of the condition and formulate individualized treatment plans.

How is endometriosis treated?

There is no cure for endometriosis, but treatments are available that can help manage pain, slow the growth of endometrial implants, and improve a woman’s chances of getting pregnant. The choice of treatment depends on symptoms, the stage of endometriosis (if known), and whether the woman intends to have children in the future.

Medications. Medications are typically the first-line treatment for endometriosis.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are used to help relieve endometriosis-related pain. NSAIDs are available over the counter and by prescription. These medications may be used in combination with other treatments, such as birth control pills.
  • Combined (Estrogen-progestin) contraceptives are often the first-line treatment, along with NSAIDs or acetaminophen, for women with pain caused by endometriosis. These contraceptives include the birth control pill (sometimes called “combined oral contraceptive pills”), patches, and vaginal rings. Estrogen-progestin contraceptives work by suppressing the ovaries, which may slow the progression of the condition and help reduce pain and menstrual bleeding.
  • Progestin, a synthetic form of the hormone progesterone, may be used by women who cannot or do not want to use estrogen-progestin contraceptives. Drugs in this category include norethindrone and medroxyprogesterone. They work by shrinking endometrial growths.
  • Gonadotrophin-releasing hormone (GnRH) agonists work by suppressing the ovaries, thereby lowering estrogen levels. They help shrink endometrial growths and reduce menstruation and endometriosis-related pain. Examples include leuprolide (given by injection) and nafarelin (a nasal spray). GnRH agonists may cause side effects such as hot flashes, vaginal dryness, reduced libido, and mood swings, among others. These side effects may be lessened by the use of norethindrone (a progestin) or an estrogen-progestin contraceptive. The use of these or other medications to reduce side effects is known as “add-back therapy.”
  • GnRH antagonists also work by lowering estrogen levels. They can help reduce pelvic pain and lessen heavy bleeding during periods. They may be used to treat people who do not respond well to NSAIDs, estrogen-progestin contraceptives, or progestins. Examples include elagolix and relugolix. These agents are oral as opposed to the agonists, which are given as an injection.
  • Danazol helps reduce endometriosis-caused pain. It resembles testosterone and therefore can cause side effects, including acne, hirsutism (excessive hair growth in women), and a deepening of the voice. Because of these side effects, danazol is not widely used.
  • Aromatase inhibitors (AIs) work by lowering estrogen levels, helping to reduce pain. Long-term use of AIs can cause bone loss and the development of ovarian cysts. They cannot be used alone and are often added to other hormonal treatments when those are not fully effective.

Surgery. Surgery may be offered to patients who have tried medications but continue to experience pain or other symptoms. Usually, endometriosis surgery can be done laparoscopically (described above in the diagnosis section), so it is minimally invasive and involves a few small incisions in the abdomen. In some cases, however, laparotomy, which involves a large incision, is necessary.

Surgical treatment of endometriosis may involve:

  • Surgical excision or ablation of endometrial implants. In this procedure, the surgeon excises (removes) scar tissue and endometrial implants. Some surgeons may also ablate, or destroy, endometrial implants. For instance, the surgeon may use a laser to vaporize the tissue or electrocautery—using electricity to heat tissue—to destroy endometrial implants.

    Often, these procedures result in reduced pain, but it is usually temporary, as endometriosis often recurs after the surgery. For instance, medications, such as those mentioned above, may be used in conjunction with surgery to suppress the function of the ovaries, which may reduce pain, lower the chance of endometriosis recurrence, and increase the chances of pregnancy.
  • Endometrioma excision. Excision, or removal, of endometriomas can help relieve pain.
  • Hysterectomy. Hysterectomy (removal of the uterus) may be an option for women with endometriosis who continue to have symptoms after trying other treatments and who do not plan to get pregnant in the future. Hysterectomy alleviates pain in 80% to 90% of women with endometriosis; however, there is a chance that endometriosis and symptoms will recur. Different types of hysterectomy are available, depending on symptoms and the patient’s age and treatment preferences:
    • Hysterectomy with bilateral salpingo-oophorectomy, or removal of the uterus, as well as ovaries and fallopian tubes. This method has the highest cure rate but typically necessitates hormone replacement to prevent menopausal symptoms.
    • Hysterectomy without bilateral salpingo-oophorectomy, or removal of the uterus without removal of the ovaries and fallopian tubes.

After undergoing a hysterectomy, women may be prescribed hormonal therapy to help prevent recurrence of endometriosis.

Fertility Treatment. The following treatments do not address symptoms related to endometriosis but are available for women with infertility or fertility issues:

  • Surgical removal or destruction of endometrial implants, which may improve fertility rates
  • In vitro fertilization (IVF), a fertility treatment in which an egg is fertilized with sperm in a laboratory dish. The fertilized egg, or embryo, is then placed in the uterus.
  • Medications that stimulate ovulation (release of an egg by the ovaries), such as clomiphene or letrozole. These medications may be used in combination with intrauterine insemination (IUI), a procedure in which sperm is placed in the uterus to increase the chances of pregnancy.

What is the outlook for people with endometriosis?

Endometriosis is a chronic condition that can cause potentially debilitating pelvic pain; heavy, painful periods; pain during sex; and infertility. The condition can significantly reduce quality of life.

There is no cure for endometriosis. In some cases, however, the condition resolves on its own, without treatment. Hormone therapy can slow the progression of the condition and reduce pain, and surgical procedures can lessen pain. But symptoms often recur after these treatments. For instance, five years after undergoing surgery for endometriosis, 40% to 50% of women are reported to have a recurrence of the condition.

Usually, symptoms go away or become milder after menopause.

What makes Yale Medicine's approach to treating endometriosis unique?

“Yale has the leading experts in endometriosis, renown worldwide,” says Dr. Taylor. “Our doctors have done the ground-breaking research that has shaped the way we treat this disease. Yale led the way in discovering that endometriosis affects the entire body, as well as developing the latest therapies for this condition. We offer the full range of treatments, including advanced diagnostic, medical therapy, including clinical trials of new treatments, and advanced laparoscopic excision surgery.”