ENDOMETRIOSIS



Page Contents

The Female Reproductive System
The Reproductive Organs
Estrogen, Progesterone, & Prostaglandins
Causes of Endometriosis
What Does Endometriosis Look Like?
Symptoms of Endometriosis
Diagnosis
Blood Tests for Endometriosis
Treatment
Hormone Medication
GnRH Analogs
Progestins
Surgery
Pregnancy
Psychological Implications

The Female Reproductive System
Endometrial tissue, whether it is inside or outside the uterus, responds to the rise and fall of estrogen and progesterone produced by the ovaries during the reproductive cycle. The roles hormones play in the function of the reproductive organs will help you understand endometriosis, its diagnosis, and treatment.

The Reproductive Organs
The uterus is a hollow organ in the center of the pelvis similar in size and shape to a pear, but usually smaller. The cervix, or lower part of the uterus, protrudes into the upper vagina. The two fallopian tubes are attached to the upper part of the uterus, one on each side. Each tube forms a narrow passageway that opens into the pelvic portion of the abdominal cavity, near the ovaries.

The ovaries are the two small glands which are similar in size to a prune and attached on each side of the uterus, beneath the fimbriated or fringed opening of the fallopian tubes. The ovary serves two functions: it produces oocytes (eggs) and secretes hormones. Each month at the time of ovulation, a mature egg is released by an ovary. Tiny, hair-like cilia on the inner lining of the fallopian tubes catch the egg and draw it inside. The egg may be fertilized during the journey through the tube toward the uterus, known as the endometrium.

Estrogen, Progesterone, and Prostaglandins
The cycle of ovarian hormone production has two phases. In the first half known as the follicular phase, estrogen plays a dominant role. During this phase, the egg, surrounded by a fluid-filled sac, matures inside the ovary. The sac is lined with cells that secrete hormones. This sac containing the egg is called a follicle. The follicle secretes a large amount of estrogen into the bloodstream, and the estrogen circulates to the uterus where it stimulates the endometrium to grow and thicken.

The second phase of hormone production begins at ovulation, midway through the cycle, when the follicle rupture and releases the mature egg into the fallopian tube. The empty follicle becomes the corpus luteum, which produces large quantities of progesterone, as well as estrogen, throughout the second half of the cycle. Traveling through the bloodstream to the uterus, progesterone complements the work begun by estrogen as it stimulates endometrial cells to mature and makes it possible for a fertilized egg (embryo) to implant.

If no pregnancy occurs, production of estrogen and progesterone will fall 10 to 14 days after ovulation and the outer two-thirds of the endometrium will be shed from the uterus as the menstrual flow. The menstrual discharge contains endometrial tissue fragments and chemical products of endometrial cells. Among these products are a group of substances called prostaglandins. These substances stimulate the uterine muscles to contract and are largely responsible for menstrual cramping. Endometriosis reacts to ovarian hormones in much the same way as the endometrium. Under the influence of estrogen and progesterone, the misplaced tissue swells and produces the same by-products, including prostaglandins. When hormone levels drop, the tissue may bleed. Unlike the normally situated endometrium that is shed from the body as menstrual discharge, this blood and tissue has no outlet. It remains to irritate the surrounding tissue.

Causes of Endometriosis
Several theories exist as to how endometriosis begins. The leading theory retrograde menstruation, the backward flow of menstrual discharge through the fallopian tubes into the pelvis. According to this theory, the endometrial cells may implant on the ovaries or elsewhere in the pelvic cavity. There is support for this theory, because woman with reproductive tract abnormalities that prevent the normal outflow of menstrual blood have an increased chance of developing endometriosis. However, retrograde flow has been noted in many woman who never develop endometriosis, so there may be other mechanisms involved.

Another possible explanation involves subtle changes of the immune system, which is responsible for clearing abnormal cells and bacteria from the body. Retrograde menstruation may overwhelm the body's ability to get rid of the endometrial cells discharged into the pelvic cavity. This may result in implantation and growth of the residual endometrial tissue. Researchers have reported measurable differences in various cells and chemicals related to the immune system in some woman with endometriosis.

Woman who have sisters or a mother with endometriosis have a greater incidence of the disease. Therefore, genetic factors are probably involved. Whether these factors pertain to changes in the immune system, as previously discussed, is not known. In spite of decades of research, the reason why some woman develop endometriosis while others do not is not completely understood.

What Does Endometriosis Look Like?
Early implants look like small, flat patches or flecks of dark paint sprinkled on the pelvic surface. The small patches may remain unchanged, become scar tissue, or spontaneously disappear over a period of months. Endometriosis may invade the ovary, producing blood-filled cysts called endometriomas. With time, the blood darkens to a deep reddish-brown color. Once a cyst has developed to this point, it is often described as a "chocolate cyst." These cysts may be smaller than a pea or larger than a grapefruit. Sudden pain may occur when a cyst bleeds into itself or bursts. The spilled fluid may cause further inflammation and the development of scar tissue.

In some cases, bands of fibrous tissue (adhesions) may bind the uterus, fallopian tubes, ovaries, and nearby intestines together. The endometrial tissue may grow into the walls of the intestine or into the tissue that separates the rectum from the vagina. When endometrial tissue grows deeply into the uterine wall, it is called adenomyosis, and the uterus becomes slightly enlarged, reddish, softer than usual, and tender. Occasionally, endometrial tissue can also invade the bladder wall. Although it may invade neighboring tissue, endometriosis is not a cancer, and cancer rarely develops in endmetriotic tissue.

Symptoms of Endometriosis
Menstrual Cramps
Dysmenorrhea or menstrual cramping may be a symptom of endometriosis. Primary dysmenorrhea, which occurs during the early years of menstruation and tends to decrease with age and after childbearing, is usually unrelated to endometriosis. Secondary dysmenorrhea, which occurs later in life and may increase with age, should be viewed as a possible warning sign of endometriosis.

Menstrual cramps are caused by contractions of uterine muscle initiated by prostaglandins released from endometrial tissue. These contractions facilitate the expulsion of menstrual fluid. When prostaglandins are released during menstruation directly into the ovaries or elsewhere in the pelvis, pain may be intensified because these pelvic tissues are sensitive to the effects of prostaglandins.

Most woman who suffer from dysmenorrhea do not have endometriosis. A puzzling feature of endometriosis is that the degree of pain is not a valid indicator of the extent of the disease. Some woman with extensive endometriosis feel no pain at all.

Two very effective treatments are available to relieve menstrual cramps associated with endometriosis. Birth control pills block ovulation and the production of progesterone, thus reducing the formation of prostaglandins. Prostaglandin inhibitors block prostaglandin production and often reduce or eliminate the pain. Ibuprofen, naproxen, and aspirin are widely used as prostaglandin inhibitors. Although they relieve pain, prostaglandin inhibitors do not affect the endometriotic tissue and thus do not cure the disease. A woman with endometriosis may notice that as the disease progresses, her periods become more painful or the pain begins earlier or lasts longer.

Pain During Intercourse
Endometriosis can cause pain during intercourse, a condition known as dyspareunia. The thrusting motion can produce pain in an ovary bound by scar tissue to the top of the vagina, or in a tender nodule of endometriosis on one of the uterosacral ligaments, which hold the uterus in place. Anchored near the top of the vagina, the uterosacral ligaments attach the lowermost portion of the uterus and cervix to the sacrum, the triangular bone at the base of the spine. Dyspareunia may also result from tender endometrial implants in the base of the pelvis near the top of the vagina.

Abnormal Uterine Bleeding
Most woman who have endometriosis report no bleeding abnormalities. Occasionally, however, the disease is accompanied by vaginal bleeding at irregular intervals. Endometriosis may exist on the intestines, on the wall of the bladder, or in surgical scars. Rarely, these pockets may release blood into the bladder or bowel during the menstrual cycle.

Infertility
In some cases, infertility is a symptom of endometriosis. However, other factors such as poor quality sperm or ovulation disorders may be involved in a couple's infertility. Some woman who have endometriosis are able to conceive, while other may be fertile due to endometriosis alone or a combination of factors.

Endometriosis may hinder conception in various ways. Endometriosis in the pelvis, for example, may inflame surrounding tissue and spur the growth of scar tissue or adhesions. Bands of scar tissue may bind the ovaries, fallopian tubes, and intestines together. Adhesions may interfere with the release of eggs from the ovaries or the pick-up of the egg by the fallopian tubes. If the ovaries are pulled away from the tubes, eggs may fail to enter the tubes on a regular basis after ovulation.

Researchers are investigating other possible links between endometriosis and infertility. Even implants located far from the tubes and ovaries can impair fertility, and there is evidence that something, perhaps prostaglandins or other chemicals, produced by these implants may interfere with ovulation, entry of the egg into the tube, and fertilization.

Studies have shown that the risk of miscarriage is higher for woman with untreated endometriosis than in those without it. The increased risk does not seem to be present for woman who have been treated. It is not known why woman with endometriosis have an increased risk of miscarriage; however, chemicals which can be toxic to the embryo have been found in the abdominal fluid of woman with endometriosis. Possible changes in the immune system might also explain the increased risk.

Diagnosis
The diagnosis of endometriosis cannot be made from symptoms alone. Your physician may suspect the disease if you are having fertility problems, severe menstrual cramps, or pain during intercourse. Remember, however, that many patients with the condition report no symptoms at all.

Pelvic Exam
Certain findings of a pelvic examination can lead your physician to suspect endometriosis. A sign that strongly suggests endometriosis is nodularity along the uterosacral ligament, which the doctor may feel during a combined vaginal and rectal exam. The nodules are often tender to the touch. An enlarged ovary can indicate the disease, especially if the doctor finds that the ovary is also fixed in position. Occasionally, endometrial implants may be visible in the vagina or the cervix. A physician may suspect endometriosis based on the history and results of a pelvic exam, but cannot confirm its presence without additional studies.

Laparoscopy
Laparoscopy, a surgical procedure that enables a physician to see inside the pelvis and inspect the reproductive organs, can verify the presence of endometriosis. Most doctors will confirm the diagnosis of endometriosis through laparoscopy before treating the disease. In fact, since endometriosis is often without symptoms, many doctors advise laparoscopy as part of the diagnostic process for all infertile woman.

During laparoscopy, a thin, lighted telescope, called a laparoscope, is inserted into the abdominal cavity through a small incision in or near the navel. Looking through the laparoscope, the surgeon can see the surface of the uterus, fallopian tubes, ovaries, and other pelvic organs. The doctor can then visually confirm the presence of endometriosis and gauge its extent. A small piece of tissue can be removed for microscopic examination at this time. This is called a biopsy.

The amount of endometriosis is assigned a numerical score at the time of laparoscopy. The score is based on the amount of superficial or deep disease found in the pelvic lining, the ovaries, and the fallopian tubes, and the amount of adhesive disease present in the pelvis. Assigning a numerical score is called staging the disease which uses a standardized system that divides endometriosis into four stages: minimal, mild, moderate, and severe. For example, a score of 1-15 indicates minimal or mild endometriosis, and a score of greater than 15 indicates moderate to severe disease. This system is useful in determining what treatment is needed.

In some cases, a physician may decide to treat endometriosis during laparoscopy. If so, he or she may make other small abdominal incisions and insert additional instruments. The surgeon may drain fluid, cut scar tissue, or burn away or vaporize endometriotic tissue with a laser beam. Also during laparoscopy, the openness, or patency, of the fallopian tubes can be checked. This is done by injecting dye through the cervix into the uterus. If the tubes are open, the dye will travel through the tubes and flow out the ends.

Other Diagnostic Procedures
In special cases, your doctor may use various imaging technologies, such as ultrasound, computerized tomography (CT scan), or magnetic resonance imaging (MRI) to get more information about the extent of endometriosis. These procedures can identify cysts or fluid within the ovaries and are usually performed in a hospital radiology department, an imaging center, or in a specially equipped doctor's office.

Blood Tests for Endometriosis
Recent studies indicate that woman with endometriosis may have increased amounts of a chemical called CA125 in their blood. Research indicates that the amount of CA125 increases as the severity of the disease increases. Unfortunately this test is not specific to endometriosis and can be positive in a number of other diseases such as fibroids, infections, recent surgery, and cancer.

Also, not all woman who have endometriosis have a positive CA125 test, especially those woman with mild disease. Therefore, it is not generally used to detect endometriosis. Other blood test are being evaluated to see if they may be more specific to endometriosis and more useful in its diagnosis.

Treatment
Your doctor will consider all the symptoms, physical findings, test results, and your goals and concerns before advising therapy. Woman with endometriosis who have few or no symptoms may require no treatment. Small endometrial implants often remain stable or may even disappear. Hormone medication, surgery, or both may be described. Doctors frequently advise patients with endometriosis to proceed with their plans to conceive. Many think that pregnancy inhibits the growth of endometriosis and causes it to regress.

Hormone Medication
The goal of hormonal treatment is to simulate pregnancy or menopause, two natural conditions know to inhibit the disease. With both treatments, the normal endometrium is no longer stimulated to grow and shed with each monthly cycle, and menstruation ceases. The growth of misplaced endometrial tissue will usually be suppressed as well.

Oral Contraceptives
To simulate the hormonal environment of pregnancy, your doctor may prescribe birth control pills to be taken in a pattern quite different from that used for contraception. One of the more effective regiments for endometriosis is to take the pills continuously, without pausing for withdrawal bleeding. If breakthrough bleeding occurs, the dose may be increased to two or three pills per day. Side effects associated with these higher dosages include nausea, water retention, and irregular vaginal bleeding. More serious complications, such as stroke, vascular problems, and heart disease, are rare but have been reported in susceptible woman.

As a contraceptive, birth control pills are administered one per day for three weeks each month, followed by a week without pills to permit menstrual flow. Many doctors feel birth control pills taken in this manner may prevent progression of endometriosis but although appealing, the theory has not been proven.

Danazol
The hormone derivative danazol is a medication frequently used to treat endometriosis. During treatment with danazol, estrogen levels are often reduced to low levels similar to natural menopause. This state is sometimes called pseudo-menopause. Danazol is thought to work indirectly by affecting the hormones produced by the brain which cause ovulation, and directly by affecting the endometrial implants.

Danazol is similar to male-specific hormones and may have side effects. These include, but are not limited to, deepening of the voice, abnormal hair growth, reduced breast size, water retention, weight gain, acne, irregular vaginal bleeding, and muscle cramps. Danazol controls pain in the majority of patients with less extensive endometriosis and may eliminate small patches of the disease. Unfortunately, large ovarian endometriomas (cysts) are generally resistant to the drug. Danazol is an expensive medication usually prescribed for six or more months and is associated with a high incidence of side effects.

GnRH Analogs
GnRH analogs comprise the newest class of hormones used for endometriosis treatment. After a few weeks of treatment, analog use leads to depletion of the pituitary hormones which direct the ovary to release estrogen. Estrogen levels fall to menopausal levels, ovulation does not occur, the endometrium does not grow, and menstruation does not occur. This results in a state called reversible menopause. Side effects of these drugs are associated with a lack of estrogen and include hot flashes, vaginal dryness, and loss of bone calcium. The medications are usually given for six months and can be administered as a daily or monthly injection or as a nasal spray. They are as effective as danazol in pain relief and in achieving pregnancy. Like danazol, large ovarian endometriomas (cysts) are generally resistant to GnRH analogs.

Progestins
Some doctors use progestins to treat endometriosis. Progestins are synthetic progesterone-like drugs prescribed as pill or injections. Side effects include water retention, mood swings, and irregular vaginal bleeding. They are considerably less expensive than the other medications. One special drawback of the injectable form is that it may inhibit fertility for an unpredictable period of time after treatment is discontinued.

Surgery
Treating endometriosis with medication has definite limitations. Medication usually controls mild or moderate pain and may eliminate small patches of the disease. But large endometrial cysts in the ovary are less likely to respond, and drugs cannot remove scar tissue. Surgery to remove adhesions, implants, or endometriomas may be needed to relieve pain or improve fertility. Even with surgery, all endometriosis may not be eradicated and sometimes postoperative medical therapy is used.

As described earlier, laparoscopy can be used as a therapeutic tool. For example, fluid can be drained and small patches of endometriosis may be destroyed using a laser or electrical current. More extensive surgery is required when scar tissue is thick or involves delicate structures.

Some patients need a combination of medical and surgical treatment. If an infertile woman with endometriosis fails to conceive even after medical and surgical treatment, in vitro fertilization may be an option. Even woman with extensive disease, whose ovaries are surrounded by adhesions, are candidates for in vitro fertilization. Ultrasound-guided techniques allow oocytes to be harvested in most cases.

While most woman exhibit improvement with therapy, 20 to 50 percent of patients exhibit signs and symptoms of recurrence five to 10 years after completion of initial therapy.

For a small number of patients who have no success with any treatments and who have completed their families, the ovaries may be removed to relieve severe and persisting pain. The uterus is also usually removed at this time (hysterectomy). Removing both ovaries minimizes the chance of recurrence, although this leaves a woman in an estrogen-deficient state. To prevent the loss of bone calcium and other menopausal symptoms due to estrogen deficiency, most of these patients will need subsequent estrogen replacement therapy. The recurrence rate for endometriosis on estrogen replacement therapy is quite low, and benefits of estrogen therapy are usually much greater than the potential risks.

Pregnancy
Although statistics are inconclusive as to whether pregnancy is therapeutic, many specialists have observed that endometriosis sometimes regresses during pregnancy. These doctors feel that the hormonal environment produced by pregnancy usually inhibits the disease. The condition may often return some time after pregnancy. However, many woman with endometriosis have difficulty getting pregnant.

Psychological Implications
Endometriosis is a disease that has emotional consequences for woman. The pain can debilitate some woman by affecting work and other relationships and disrupting normal activities. Sexual intercourse can be painful; some woman lose interest in sex to avoid the discomfort. In addition, the hormonal treatments for endometriosis can affect sexuality and be emotionally difficult. The side effects of these medications, some of which mimic menopause, can cause depression and inhibit sexual desire in some woman. The understanding and support of a partner, family, and friends are important to any woman with endometriosis. Support groups have formed to help woman deal with endometriosis and may be available in your area.

Conclusion
Endometriosis is a disease affecting millions of woman throughout the world. For many, the condition goes unnoticed. But for others, it demands professional attention, especially when fertility is impaired or pain affects the lifestyle. Choosing a qualified physician who is familiar with the latest developments in endometriosis management is your best strategy. The physician you choose will recommend the most appropriate course of treatment based on your personal situation.

Reprinted with permission from the
American Society for Reproductive Medicine




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