MEDICAL CONDITIONS
Endometriosis
What is endometriosis?
Endometriosis is a growth of cells similar to those that form the inside of the uterus (endometrial cells) outside of the uterus. Endometrial cells are the same cells that are shed each month during menstruation . When endometrial cells grow outside the uterus, endometriosis results. These cells attach themselves to tissue outside the uterus and are called endometriosis implants. The implants are most commonly found on the ovaries, the fallopian tubes, outer surfaces of the uterus or intestines, and on the surface lining of the pelvic cavity. They can also be found on the liver, vagina, old surgery scars, and even in the lung or brain. Endometrial implants are generally benign (not cancerous).
Endometriosis affects women in their reproductive years. Endometriosis is estimated to affect over 1 million women (estimates range from 3% to 18% of women) in the United States. It is one of the leading causes of pelvic pain and reasons for laparoscopic surgery and hysterectomy in this country. While the mean age at diagnosis is around 25-30 years, endometriosis has been reported in girls as young as 11 years of age.
What causes endometriosis?
The cause of endometriosis is unknown. There are several theories, but none of them have been proven. The main current theory is that the endometrial tissue is deposited in unusual locations by backing up the fallopian tubes and into the pelvic and abdominal cavity during menstruation (retrograde menstruation). The cause of retrograde menstruation is not clearly understood. But retrograde menstruation is not the entire story. Many women have retrograde menstruation in varying degrees, yet not all of them develop endometriosis.
What are the symptoms of endometriosis?
Most women who have endometriosis do not have symptoms. Of those who do experience symptoms, the common symptoms are pain (usually pelvic) and infertility . Pelvic pain usually occurs during or just before menstruation and lessens after menstruation. Some women experience pain or cramping with intercourse, bowel movements and/or urination. Even pelvic examination by a doctor can be painful. The pain intensity can change from month to month, and vary greatly among women. Some women experience progressive worsening of symptoms, while others can have resolution of pain without treatment.
Pelvic pain from endometriosis is the sum of potential factors. Pelvic pain in women with infertility depends partly on where the implants are located. Deeper implants and implants in areas with many pain-sensing nerves may be more likely to produce pain. The implants may produce substances that circulate in the bloodstream and cause pain. Lastly, endometriosis scarring can produce pain.
Endometriosis can be one of the reasons for infertility in otherwise healthy couples. When laparoscopic examinations are performed for infertility evaluations, endometrial implants can be found in some of these patients, many of whom may not have painful symptoms of endometriosis. Doctors believe that endometriosis inflammation and scarring in these patients can cause distortion of the female reproductive organs (such as obstruction of the fallopian tubes), resulting in infertility. However, the severity of the disease is not necessarily directly related to the degree of infertility. Infertility researchers have increasingly realized that infertility is affected by multiple factors aside from endometriosis. It does appear certain that total inability to conceive is only rarely a direct result of endometriosis.
Other symptoms related to endometriosis include lower abdominal pain , diarrhea and/or constipation , low back pain , irregular or heavy menstrual bleeding, or even blood in the urine. Rare symptoms of endometriosis include chest pain or coughing blood due to endometriosis in the lungs, headache and/or seizures due to endometriosis in the brain.
There is no relationship between severity of pain and how advanced the endometriosis is (the "stage" of endometriosis). Likewise there is no relationship between the stage of endometriosis and the likelihood a woman will have a good response to treatment.
How is endometriosis diagnosed?
Endometriosis can be suspected based on symptoms of pelvic pain and findings during physical examinations in the doctor's office. Occasionally, the doctor can feel nodules (endometrial implants) behind the uterus and along the ligaments that attach to the pelvic wall. At other times, no nodules are felt, but the examination itself causes unusual pain or discomfort. Unfortunately, neither the symptoms nor the physical examinations can be relied upon to establish the diagnosis of endometriosis. Imaging studies, such as ultrasound , can be helpful in studying the pelvis, but still cannot accurately diagnose endometriosis. Direct visual inspection and tissue biopsy of the implants are necessary for accurate diagnosis.
As a result, the only accurate way of diagnosing endometriosis is at the time of surgery (either by open standard laparotomy or laparoscopy ). Laparoscopy is the most common surgical procedure for the diagnosis of endometriosis. Laparoscopy is a minor surgical procedure done under general anesthesia or in some cases local anesthesia. It is usually performed as an out-patient procedure (the patient going home the same day). Laparoscopy is performed by first inflating the abdomen with carbon dioxide through a small incision in the navel. A long, thin instrument ( laparoscope ) is then inserted into the inflated abdominal cavity to inspect the abdomen and pelvis. Endometrial implants can then be directly visualized. During laparoscopy, biopsies (removal of tiny tissue samples for examination under a microscope) can also be performed for a diagnosis. Sometimes biopsies obtained during laparoscopy show endometriosis even though no endometrial implants are visualized during laparoscopy.
Pelvic ultrasound and laparoscopy are also important in excluding malignancies (such as ovarian cancer ) that can mimic endometriosis.
Unfortunately, no blood tests can accurately diagnose endometriosis.
How is endometriosis treated?
Endometriosis can be treated with medications and/or surgery. The goal of endometriosis treatment include pain relief and enhancement of fertility. Treatments discussed below will address 3 types of treatment: treatment of the endometriosis implants themselves, treatment of the pain, and treatment of the infertility.
Treatment of endometriosis implants and scarring
Progestins are also used for medical treatment of the endometriosis implants. They cause shrinkage of endometrial tissue. The most common progestin used for endometriosis treatment is medroxyprogesterone acetate. Side effects, which are reversible with stopping the medication, include breast tenderness, uterine bleeding, and depression . Side effects may decrease with continued treatment.
Estrogen and progesterone in combination are sometimes used to treat endometriosis. Most commonly the combination used is in the form of the oral contraceptive pill (OCP). No one brand is better than another brand of OCP for endometriosis treatment. The OCP's work for endometriosis by "fooling" the body into thinking it is pregnant. Sometimes women who have severe menstrual pain are asked to take the OCP continuously, meaning skipping the placebo (sugar pill) portion of the cycle. Continuous use in this manner will free a woman of having any menstrual periods at all. Weight gain, nausea, and irregular bleeding are usual mild if they occur at all. OCP's are often well-tolerated in women with endometriosis.
Danazol causes anovulation, which means it interferes with ovulation . By causing anovulation, it prevents production of hormones that would trigger endometrial implant growth and/or pain. It has side effects that include unwanted hair growth, mood changes, voice deepening, and unfavorable cholesterol changes. Rarely, serious liver damage can occur. The voice changes and liver damage may not be reversible with halting of the medication use.
Gonadotropin-releasing agonists (GnRH agonists) alter the hormone levels in the body to halt the production of estrogen. As a result menstrual periods stop, in a way mimicking menopause . Nasal and injection forms of GnRH agonists are available. The side effects are a result of the lack of estrogen, and include hot flashes , vaginal dryness, irregular vaginal bleeding , mood changes, fatigue, and loss of bone density ( osteoporosis ). Fortunately, by adding back estrogen and progesterone, similar to treating menopause, we can avoid many of the annoying estrogen deficiency side effects. "Add back therapy" is the term that refers to this modern way of administering GnRH agonists along with estrogen and progesterone in a way to keep the treatment successful but avoid most of the side effects.
Surgery is also used to treat endometriosis implants themselves. Laparoscopy is the most recent technique that has the advantages of shorter hospital stays and recovery time compared to older procedures. The surgery goal in endometriosis is to bring back a woman's normal abdominal and pelvic anatomy and destroy or remove all visible endometriosis tissue. No particular instruments or methods currently in use are yet proven to have any advantage over the others.
Pain relief
Nonsteroidal anti-inflammatory drugs or NSAIDs (such as ibuprofen or naproxen sodium) are commonly prescribed to help relieve pelvic pain. The medications will also help relieve menstrual cramping. These analgesic medications have no effect on the endometrial implants. However, they do decrease prostaglandin production, and prostaglandins are well-known to have a role in production of pain sensation. Because the diagnosis of endometriosis is only definite after a woman undergoes surgery, there will of course be many women who are suspected of having endometriosis based on the nature of their pelvic pain symptoms. In such a situation, `NSAID's are the most common treatment used. If they work to control pain, no other procedures or medical treatments are needed. If they do not relieve the pain, additional evaluation and treatment generally occur.
Medroxyprogesterone acetate (Danazol), GnRH agonists with add-back therapy, and OCP's have all been used to give pain relief from endometriosis-associated pain. These medications are described above. All of these medications work for pain, and it is likely that they all work similarly well.
In addition to the use of surgery to remove or destroy endometriosis tissue (discussed above), surgery is also used to relieve pain associated with endometriosis. However, procedures are different when the goal is pain relief. Pain-sensing nerves are destroyed or removed via a few different types of techniques. Unfortunately, research is lacking to tell us whether these procedures should be routinely performed in all women undergoing removal or destruction of endometriosis tissue, or rather whether we should be picking certain characteristics of a woman's history to guide us in selecting women who are likely to benefit from certain specific procedures. Women who have had surgery for endometriosis should consider taking medication after surgery to help maintain symptom relief.
Infertility in women with endometriosis
Because of the distortion it causes, severe endometriosis can block the needed access of the egg to the fallopian tube. Women with advanced endometriosis have a low chance of getting pregnant and are therefore commonly recommended to undergo surgery with the goal of destroying or removing abnormal endometriosis tissue and scars. However, women with milder forms of endometriosis may not actually be at higher risk of infertility compared to other women. This issue is very controversial. Specifically, we don't know whether the mild endometriosis is actually causing infertility. As a result it would be difficult to routinely recommend extensive surgery to a women with mild endometriosis if we don't even know if that mild endometriosis is the cause of her infertility. It is not yet determined whether surgery increases fertility rates in women with mild endometriosis. It is likely that surgery only provides small benefit in this situation.
Unfortunately, none of the medications reviewed above have any impact whatsoever on infertility in women with endometriosis. In fact, the medications will actually inhibit a woman's ability to conceive during the time a woman is using them. Essentially, a woman with endometriosis who is struggling to get pregnant only has 2 choices: ovulation induction and assisted reproduction techniques. Ovulation induction involves using medications (GnRH agonists, follicle-stimulating hormone, luteinizing hormone , clomiphene citrate) with or without intrauterine insemination to increase fertility. Intrauterine insemination is placement of the fertilized egg directly into the uterus. Research has shown that ovulation induction with or without intrauterine insemination can increase fertility in women with endometriosis-associated infertility. In-vitro fertilization, in contrast, has not yet been supported with very much research in women with endometriosis. It may be indicated in women with advanced endometriosis, but may not increase pregnancy rates in women with mild endometriosis. It is still unclear what is the optimal duration of in vitro fertilization therapy in women with endometriosis.
In summary, both medication and surgery can help treat the pelvic pain of endometriosis. All the medications commonly used are generally equally effective. Surgery techniques continue to evolve, and it is likely that in the future different procedures will be used based on the specific type and severity of symptoms an individual woman experiences. The role for a combination of surgery and medication is still in flux. If NSAID's or OCP's relieve pain, they are continued. If they fail to relieve pain, other medications are available. If these other medications fail, surgery (laparoscopy) may be recommended to confirm the diagnosis and also for treatment. In contrast, the infertility of endometriosis is often addressed with a combination of surgery and assisted reproduction techniques, because medications are not effective. Surgery to bring back the normal anatomy and remove abnormal endometriosis tissue may be all that is necessary for a successful pregnancy. If additional measures are needed, assisted reproduction techniques are available. - In patients with endometriosis, cells that normally grow inside the uterus (womb), instead grow outside the uterus.
- The cause of endometriosis has not been identified, although several theories are popular.
- Most women with endometriosis have no symptoms.
- Pelvic pain during menstruation or ovulation can be a symptom of endometriosis, but may also occur in normal women.
- Endometriosis can be suspected by the practitioner by the woman's pattern of symptoms, and sometimes during a physical examination, but the definite diagnosis must be confirmed by surgery, usually laparoscopy.
- Treatment of endometriosis includes medication and surgery for both pain relief and treatment of infertility.
Medical Author: Leon J. Baginski, MD, FACOG
Medical Revision: Carolyn J. Crandall, MD, FACP
Medical Editor: William C. Shiel, Jr., MD, FACP, FACR
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