Endometriosis

Cause  ·  Incidence  ·  Symptoms  ·  Physical Findings/Lab  ·  Diagnosis  ·  Natural History  ·  Association with Infertility  ·  Principles of Management  ·  Birth Control Pills  ·  GNRH Antagonists  ·  Danazol  ·  Progestins  ·  Conservative Surgery  ·  Definitive Surgery  ·  The Military Setting

Endometriosis is a common gynecologic problem. It is defined as the abnormal location of normal endometrial tissue in the body, and is associated with pain, scar tissue formation, and infertility.

Endometrium is normally located within the uterine cavity, lining the interior walls of the uterus. In response to the normal cyclic hormonal events, the lining thickens, then splits off its most superficial layer, which is shed during the menstrual flow.

Women with endometriosis have patches of "normal" endometrium located elsewhere in the body. The most common locations for these implants are on the:

• Ovary

• Anterior and posterior cul-de-sac

• Posterior broad ligament

• Uterosacral ligament

• Uterus

• Fallopian tube

• Sigmoid colon

• Appendix

• Round ligament

However, endometriosis can be found virtually anywhere in the body, including sites quite remote from the pelvis (lung, vertebra, skin).

Cause of Endometriosis
The specific cause is not known, but several theories can, in part, explain the existence of endometriosis. Two of the more popular theories are:

• Implantation Theory:  During menses, some reflux of menstrual products back through the fallopian tubes occurs. Viable endometrium can land on a favorable site and, if tolerated by the patient's immune system, can establish enough of a blood supply to live and respond to the cyclic ovarian hormones.

• Coelomic Metaplasia Theory: The peritoneal cavity contains some cells that have retained their undifferentiated nature and, given the proper stimulus, may grow and differentiate into endometrial cells.

Incidence
 

The incidence of endometriosis in the general population is not known. For women undergoing gynecologic surgery, the incidence varies, undoubtedly depending on the population, type of surgical procedure, and the skill and diligence with which endometriosis is sought. The frequency with which endometriosis is found varies from:

• 6% to 43% of women undergoing sterilization

• 12% to 32% of women undergoing laparoscopy for pelvic pain

• 21% to 48% of women undergoing laparoscopy for infertility

• 50% of teenagers undergoing laparoscopy for chronic pelvic pain or dysmenorrhea

Symptoms
Classically, women with symptomatic endometriosis present with a chronic (more than 6 month) history of steadily worsening pelvic pain. It is worse with menses and sometimes worse with ovulation. It may be focal or diffuse, but its location is usually constant. The pain may be aching, cramping, or both at different times.

A second classical symptom is painful intercourse on deep penetration. The patient will tell you she feels him hitting something deep inside that is very tender. If she re-directs the angle of his thrusting or limits the depth of his penetration, she may be able to avoid the pain.

Less common is painful bowel movements. If implants are located on the rectosigmoid or close to it (uterosacral ligaments), then she may experience pain while actually passing her stool.

About half of the women who are demonstrated to have endometriosis have no symptoms at all.

Physical Findings and Lab
Classical physical findings include:

• Unusual tenderness and thickness (a dough-like consistency) in the adnexal areas.

• Tender nodules along the uterosacral ligament, usually appreciated best on combined recto-vaginal bimanual exam.

• Tender nodules at the junction of the bladder and the uterus.

• Tender nodules over the uterine corpus.

Many women (particularly those with asymptomatic endometriosis) have no positive physical findings.

There are no laboratory tests that are specific for endometriosis. However:

• Some women with endometrioisis have a persistent complex or solid adnexal mass on ultrasound, CT or MRI. These endometriomas can assume a passable resemblance to almost any adnexal neoplasm. This means that the differential diagnosis for virtually any adnexal mass would include endometriosis.

• Most women with endometriosis will have an elevated serum CA-125. This chemical is released any time there is peritoneal irritation from any source.

Diagnosis
The diagnosis can be established clinically, surgically, and/or histologically.

• Clinical Diagnosis is established by a convincing history that is reasonably close to the classical description, accompanied by physical findings that are very suggestive of endometriosis. Making a clinical diagnosis has the advantage of avoiding surgery, but the disadvantage of being wrong from time to time.

• Surgical Diagnosis is obtained by visualizing typical endometriosis implants in the typical places endometriosis tends to grow in. The visual indicators of endometriosis include deep red, slightly hemorrhagic sites, white puckering of the peritoneum, brown "powder burns," translucent blebs, defects in the peritoneum, polypoid growths, and dense scarring of the ovaries, tubes and cul-de-sacs. This may be done through laparoscopy or laparotomy. A surgical diagnosis is more reliable than a clinical diagnosis, but not always consistent with a histologic diagnosis.

• Histologic diagnosis depends on the microscopic confirmation of endometrial glandular and stromal cells in an ectopic location. This is highly specific, but requires surgical risk to obtain the specimen. At times, the endometrial cells can be elusive, particularly if the patient has been treated with medications to suppress endometriosis. It is not uncommon for there to be obvious endometriosis at the time of surgery, yet the biopsies will be negative.

Some gynecologists feel that before initiating therapy, all patients in whom the diagnosis of endometriosis is entertained should undergo laparoscopy. Others feel that this is an unnecessary and dangerous over-reaction and reserve laparoscopy for those in whom conservative management has failed or for whom there are other indications for laparoscopy, such as infertility.

Natural History
Untreated, endometriosis can worsen, regress or stay the same, but more often is progressive. Some life events have a favorable influence on endometriosis. Pregnancy and breast-feeding favorably influence endometriosis. Birth control pills, even if taken cyclically, usually make endometriosis better (particularly minimal, mild or moderate).

At menopause, deprived of its hormonal support, endometriosis usually regresses, regardless of whether or not estrogen replacement therapy is used.

Endometriosis has no malignant potential. It is a problem only because of its potential for causing pain and scarring, and its association with infertility.

Association with Infertility
Generations of gynecologists have recognized that among infertile women, endometriosis is relatively common. Probably between 25% and 50% of infertile women will have at least some degree of endometriosis present.

It is easy to understand how someone with severe endometriosis, including dense pelvic adhesions, might experience difficulty achieving a pregnancy. More difficult to understand is why someone with one tiny endomtriosis implant on the sigmoid colon would also experience infertility. The answer may lie in the complexity of endometriosis.

Rather than blaming endometriosis for the infertility, it is certainly possible that there is some other, yet unexplained factor, that predisposes the woman towards developing endometriosis and also predisposes her toward infertility. Severe cervical stenosis, for example could promote a large amount of retrograde menstruation (setting her up for endometriosis) and also interfere with normal sperm transport through the cervix (decreasing her chance of fertility).

Principles of Management
There is no single best management for all women with endometriosis. Treatment must be individualized. The primary factors that we consider, however are:

• The need for preserving childbearing capacity

• The severity of her symptoms

• Presence or absence of infertility as a clinical concern for her.

• Age

A 35 year old woman with severe symptoms and no desire for any further childbearing might be best served by a hysterectomy. The same woman at age 50 might prefer to go with medical therapy until menopause, when the symptoms will go away. The same woman at age 40, but with mild symptoms might do well on birth control pills.

Birth Control Pills
Birth control pills exert a number of beneficial effects, particularly on mild or moderate endometriosis. They generally:

• Reduce the heaviness of the menstrual and its duration, reducing the amount of retrograde menstrual products.

• Provide a powerful decidualizing effect on the implants by virtue of their strong progestin. This discourages further growth of pre-existing implants.

• Reduce the levels of circulating estrogens, particularly estradiol. By inhibiting ovarian function and providing "add-back" estrogen, the s. estradiol levels in the blood are usually a little lower than before the BCP was taken. Lower estrogen levels ease some of the hormonal stimulatioin of the implants.

• When taken continuously, stop the episodic hormonal withdrawal bleed that occurs both with normal endometrium and with endometrial implants.

For severe endometriosis, other more powerful medications or surgery are often needed to be effective.

It usually takes 3-6 months of continuous OCPs for the patient to notice a significant benefit and up to 12 months to achieve maximum benefit.

OCPs are relatively inexpensive, making this treatment choice very affordable for most patients.

GnRH Agonists
Luprolide induces a temporary and artificial menopause, with inhibition of ovarian function. The bad part of that are the side-effects, including hot flashes, night sweats, vaginal dryness and other menopause symptoms. The good part is that deprived of their estrogen support, endometriosis implants regress and may disappear.

Many physicians will provide add-back estrogen to their endometriosis patients who experience significant menopausal symptoms. This add-back estrogen is a very small dose and does not apparently reduce the beneficial impact of Luprolide, but does provide significant relief of their annoying symptoms.

Most patients taking this medication will notice a significant improvement of their symptoms in 3 months and by 6 months feel very good. After 6 months, the medication needs to be stopped, although another course can be taken later, if needed.

Luprolide is moderately expensive, a potentially limiting factor for some patients.

Danazol
This is a cousin of testosterone and has both direct and indirect effects on endometriosis. It:

• Directly inhibits endometriotic implant growth through its powerful decidualization properties.

• Suppresses the secretion of pituitary gonadotropins, resulting in inhibition of ovarian function and lower estrogen levels.

• Blocks steroidogenic enzymes.

The two main problems with Danazol when used for treatment of endometriosis are its high cost and significant side-effects (weight gain, masculinizing side-effects and depression). However, it is very effective in treating endometriosis and few patients stop it, even if they experience side-effects. It is normally taken for about a year before stopping it.

Progestins
Progestins can inhibit pituitary release of gonadotropins, blocking ovarian function, and have a strong decidualizing effect on endometrial implants, limiting their growth. Both properties are valuable when treating endometriosis.

Progestins seem to be about as effective in treating endometriosis as OCPs, but are somewhat less well tolerated. Weight gain and breakthrough bleeding are the biggest problems. It is not particularly expensive, and is a reasonable choice for someone wishing to avoid surgery and OCPs, but intolerant of Danazol or Luprolide.

Conservative Surgery
Conservative surgery means surgically removing as much endometriosis as possible, but within the limitations of preserving childbearing capacity as much as possible. This means leaving the uterus, tubes and ovaries largely intact, but removing all endometriosis implants that can safely be removed.

Conservative surgery is the best choice for most infertility patients as none of the non-surgical treatments has been found to improve the patient's fertility at all. In contrast, conservative surgery will achieve 40% to 60% post-surgical pregnancy rates, depending on the severity of the disease.

Definitive Surgery
Definitive surgery involves a hysterectomy, with or without removal of the tubes, ovaries, and other sites of endometriosis. Definitive gives the greatest chance of permanently curing the pain of endometriosis, but necessarily involves giving up any chance for future childbearing.

Controversial is the role of removal of the ovaries. If you remove them, you will achieve a slightly higher cure rate than if you leave them alone. However, you will surgically create menopause and without treatment, create menopausal symptoms. For this reason, many gynecologists prefer to leave the ovaries in.

Other gynecologists prefer to remove the ovaries, with the intention of starting estrogen replacement therapy immediately after surgery. The addition of these small amounts of estrogen are apparently not enough to further feed the endometriosis.

The Military Setting
Patients presenting in an advance military setting will generally complain of chronic pelvic pain, of at least 6 months duration, that is significantly worse during their menstrual flow. They may have painful intercourse on deep penetration and may experience painful bowel movements. Sometimes, the only symptom is progressively worse dysmenorrhea. Usually, there will be at least focal tenderness in the adnexal areas, and sometimes generalized tenderness.

These patients will benefit from a course of antibiotic (doxycycline, ciprofloxacin, zithromax, or comparable drugs capable of clearing chronic PID), and OCPs. The antibiotic will insure that chronic PID is not a source of their pain, and the OCPs will be effective at limiting their symptoms and treating the endometrioisis. Most effective in this setting will be continuous OCPs, to totally suppress the menstrual cycle.