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
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
