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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:
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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:
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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.
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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:
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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.
Endometrioma of Right Ovary
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:
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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:
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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.
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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:
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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:
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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
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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:
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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 sideeffects. 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.