Endometriosis is the growth of skin tissue that lines the uterus (called endometrium), at a site outside of the uterus, usually on the lining of the abdominopelvic cavity called the peritoneum. The growing tissue includes both glands and supporting tissue recognizable under the microscope as endometrium but not in the usual location inside the uterus.
The tissue growths are like seeds that implant outside of the uterus and undergo hormonal stimulation just like the tissue inside the uterus and grow and slough monthly. These areas range mostly from the size of a pin head to the size of a pencil eraser although sometimes the lesions can can become quite large like an egg, apple or even grapefruit in size. The endometriosis growths can cause chronic or acute pelvic pain from leakage of their contents (mostly blood and tissue) or from just swelling up with nowhere for the blood and sloughed tissue to go. Also, monthly swelling of extrauterine endometrial tissue may cause inflammation of the nearby tissue and discomfort secondary to the release of irritant chemicals such as prostaglandins, interleukins, or tumor necrosis factor that come from the endometrial tissue (1). This irritation produces symptoms of pelvic pressure or bowel bloating.
While one might expect that a larger area of disease would cause more pain, studies to date show no relationship between the extent of endometriosis, known as stage, and the amount of pain a woman experiences. Women can have severe pain from small areas of endometriosis and very little discomfort even with involvement of large areas in the pelvic cavity. The American Fertility Society developed a staging system for endometriosis based on weighted points. It was revised in 1996 and is supported now by the American Society of Reproductive Medicine. An example of the staging system explains it best.
With respect to infertility, however, data does support a relationship between the amount of disease and the decreased ability to conceive a pregnancy. More advanced endometriosis disease produces more difficulty conceiving (1).
Is it common?
Endometriosis is estimated to be present in anywhere from 2-22% of asymptomatic, reproductive age women, in 40-60% of women who have developed the new onset of severe menstrual cramps, and in 20-30% of women with subfertility. The peak incidence appears to be at age 40. (5) In one group of subfertility patients, a higher incidence of endometriosis was found at laparoscopy, 43%, with about half of those having stage 1-2 disease and half having stage 3 and 4 disease (7).
It is not a new or recent disease of modern living. Endometriosis was described in European documents over 300 years ago. In 1690, a German Physician named Daniel Shroen in a book entitled Dusputatio Inaguralis Medica de Ulceribus Ulceri recorded the first description. Later, in 1860 another German, Carl von Rokitansky, wrote a detailed description of what we now term endometriosis. (3)
The predominant clinical features of endometriosis are cyclical (mostly monthly), pelvic pain, non-cyclical pelvic pain, backache, pain during intercourse, painful urination, painful bowel movements and infertility. (1, 5)
The definitive diagnosis is made from microscopic examination of tissue biopsies taken at time of laparoscopy or other surgical exploration. Visualization by the surgeon of what looks to be endometriosis is only confirmed about 77% of the time by pathologic examination of the biopsies (8). Histologic confirmation of endometriosis in a biopsy specimen is therefore the gold standard for diagnosis.
Endometriosis has been reported in almost all tissues such as the bowel, liver, lung, brain and skin. Symptoms would depend upon which tissue is involved and often occur or worsen monthly with the menstrual cycle.
Endometriosis is the result of one or a combination of processes including the following (1):
retrograde menstruation-at the time of menses - blood and endometrial tissue flows backwards out the tubal opening into the pelvis and implants on other pelvic or abdominal structures;
lymphatic and/or vascular spread - microscopic tissue gets into the lymph channels or vascular channels and spread throughout the pelvis and/or body;
reactivation of arrested embryonic cells - small foci of totipotential stem cells from the developmental process become reactivated and differentiate into endometrial tissue;
other unknown mechanisms.
The precise way in which these elements are formed is unknown, but several theories exist. Risk factors known to be associated with endometriosis include the following:
Genetics - an affected mother or sister doubles your risk;
Hormonal status - increased circulating estrogen and prolonged or heavy menses increases your risk, but to an unknown degree;
Lifestyle - obesity and smoking increase your risk, also to an unknown degree. (1)
The tumor marker CA-125 can be positive with endometriosis but is not useful in diagnosing endometriosis, even with ovarian involvement (1). CAT scan, MRI imaging studies, and even ultrasound are not indicated to diagnose endometriosis. They are only helpful if ovarian endometriomas (blood filled cysts of the ovary) are seen, but then the differential diagnosis expands to include all other ovarian tumors both benign and malignant.
It is thought that endometriosis results in subfertility because the extrauterine implants undergo cyclical bleeding like intrauterine endometrial tissue. This cyclical bleeding causes not only pain but it can result in inflammation, adhesions, fibrosis, distorted pelvic anatomy, endocrine abnormalities, abnormal immune function, altered pelvic chemical environment, and possibly interferes with embryo implantation. (1)
In one study in which laparoscopy was performed 12 months after diagnosis with no treatment in between, it was found that the endometrial implants resolved spontaneously in a quarter, deteriorated in nearly half, and were unchanged in the remainder.
Goals of therapy (Rx)
The goals of treatment should be to reduce pain, increase fertility (if desired), and decrease the amount of surgical intervention needed.
1st choice therapy
The choice of therapy that is best, or first line, should be individualized based on the patient. For example, the treatments for a patient wanting to have children may differ greatly from the treatment for a patient who has completed their childbearing.
For pain as the main symptom
If endometriosis is strongly suspected on the basis of symptoms or if it has been diagnosed as minimal or mild (Stage 1 or 2) by laparoscopy or other surgical exploration, then treatment is primarily suppression of the normal, cyclical ovarian function induced by ovulation. For the patient desiring pain relief and who may or may not have completed childbearing, continuous oral contraceptive pills (OCPs) or DepoProvera® injections (9) and non steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen are generally used for 3-6 months (1). If the goal of this therapy is not being met in 3-6 months and endometriosis is just suspected, definitive diagnosis with laparoscopy is indicated before any further treatment.
If endometriosis cysts inside the ovary are found (endometriomas), removal of the cyst results in a lower pain recurrence rate and higher pregnancy rate than just drainage of the cyst (10).
For subfertility - failure to conceive over 12 months of trying - as the main symptom
Surgery should be performed to diagnose the presence and extent of any endometriosis lesions. Tubal patency should be established. Any endometriosis of Stage 3 or 4 (moderate or severe) that restricts normal movement of the Faloppian tubes and/or ovaries, or any endometriosis or scarring involving the small bowel or large intestine should be surgically removed if possible. Scar tissue (adhesions) should be freed up to allow the tubes and ovaries to move as freely in the pelvis. Visible endometriotic implants should be surgically excised or ablated using laser or electrical or thermal cautery. With minimal or mild endometriosis (stage 1 or 2) laser ablation or surgical resection, does not appear to improve fertility rates at all (11). Therefore other causes of infertility have to be ruled out but most treatments end up with the same 45-50% pregnancy rate (12). After a certain amount of time attempting unsuccessfully to conceive, in vitro fertilization may be the best option for patients with endometriosis (13).
Sometimes endometriosis is diagnosed during surgery for problems unrelated to pain or infertility. Because this disease will progress and become more extensive in a certain percentage of cases, hormonal treatment is recommended to alter the natural course.
Other therapies used
For pain as the main symptom
For a patient who is sure that her childbearing has been completed, hysterectomy and removal of the ovaries may provide symptomatic relief from the pain. Studies have shown that women experience up to 92% relief of symptoms after undergoing a hysterectomy and oophorectomy for endometriosis. If child bearing is not completed or hysterectomy is not an option, gonadotrophin releasing hormone stimulator (GnRH), like leuprolide (Lupron®), may be used in place of OCPs or DepoProvera®. It is very effective in lessening the pain of endometriosis, but there are more side effects than progestin or estrogen and progestin ovulation suppression. Lupron® produces severe hot flashes and depression (14). GnRH treatment should probably be given with "add-back" therapy (menopausal estrogen and progestin) because it lessens the hot flashes but it is just as effective at reducing endometriosis implants as when given alone without the add-back (15).
Laparoscopic presacral neurectomy does not seem to reduce pain with sex, back pain or pain on the right of left sides any more than just laparoscopic resection of the endometriosis alone; midline menstrual cramps may be helped however (16, 17).
For subfertility as the main symptom
For any documented stage of endometriosis, assisted reproductive technology procedures such as in vitro fertilization, or oocyte donation may be options. (1) Adoption is also an alternative after a certain amount of time has been spent with trying to conceive unsuccessfully.
Ovulation suppression to enhance fertility after discontinuing it does not seem to improve conception (18).
Patients should avoid chronic use of narcotic medications.
Reason for Rx choices
A patient’s need for symptomatic pain relief, or subfertility should dictate how treatments should be individualized. Also, it should be pointed out that the treatments that help control pain best, OCP’s and GnRH agonists, work by suppressing ovulation and themselves keep patients from conceiving. It is very important that a woman and her physician communicate and agree upon the goals of treatment for endometriosis, so that there is the best possible outcome with the treatments available.
Birth control pills alone seem to be as effective at reducing pain from endometriosis as GnRH medications (19). Since they are less expensive and have less side effects, they are the first choice therapy over GnRH agonists.
1. Adamson, G. D.: A 36-year-old woman with endometriosis, pelvic pain, and Infertility. JAMA 1999; 282:2347-54
2. Redwine DB: Ovarian endometriosis: a marker for more extensive pelvic and intestinal disease. Fertil Steril 1999; 72(2):310-5
3. Knapp VJ: How old is endometriosis? Late 17th-and 18th-century European descriptions of the disease. Fertil Steril 1999; 72(1):10-4
4. Olive DL, Pritts EA: Drug therapy: Treatment of endometriosis. N Engl J Med 2001. 26;345(4):266-75
5. Farquhar, CM: Endometriosis. BMJ 2000 27;320(7247):1449-52
6. Prentice A: Regular review: Endometriosis. BMJ 2001 14;323(7304):93-5
Images of endometriosis