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Endometriosis

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Signs and symptoms

Pelvic pain

A major symptom of endometriosis is recurring pelvic pain. The pain can be mild to
severe cramping that occurs on both sides of the pelvis, to the lower back and rectal
area and even down the legs. The amount of pain a woman feels is not necessarily
related to the extent or stage (1 through 4) of endometriosis. Some women will have
little or no pain despite having extensive endometriosis affecting large areas or having
endometriosis with scarring. On the other hand, women may have severe pain even
though they have only a few small areas of endometriosis. However, pain does typically
worsen with severity. Symptoms of endometriosic-related pain may include:
 0 dysmenorrhea ± painful, sometimes disabling cramps; pain may get worse over
time (progressive pain), also lower back pains linked to the pelvis
0 chronic pelvic pain ± typically accompanied by lower back pain or abdominal pain
0 dyspareunia ± painful sex
0 dysuria ± urinary urgency, frequency, and sometimes painful voiding

~nfertility

gany women with infertility have endometriosis. As endometriosis can lead to

anatomical distorsions and adhesions (the fibrous bands that form between tissues and
organs following recovery from an injury), the causality may be easy to understand;
however, the link between infertility and endometriosis remains enigmatic when the
extent of endometriosis is limited. It has been suggested that endometriotic lesions
release factors which are detrimental to gametes or embryos, or, alternatively,
endometriosis may more likely develop in women who fail to conceive for other reasons
and thus be a secondary phenomenon; for this reason it is preferable to speak of
endometriosis-associated infertility in such cases.

Other

Other symptoms may be present, including:

0 nausea, vomiting, fainting, dizzy spells, vertigo

0 frequent or constant menstrual flow
0 chronic fatigue
0 heavy or long uncontrollable menstrual periods with small or large blood clots
0 some women may also suffer mood swings
0 extreme pain in legs and thighs
0 back pain
0 mild to extreme pain during intercourse
0 extreme pain from frequent ovarian cysts
0 pain from adhesions which may bind an ovary to the side of the pelvic wall, or
they may extend between the bladder and the bowel, uterus, etc
0 extreme pain with or without the presence of menses
0 premenstrual spotting
0 mild to severe fever
0 headaches
0 depression
0 hypoglycemia (low blood sugar)
0 anxiety

In addition, women who are diagnosed with endometriosis may have gastrointestinal
symptoms that mimic irritable bowel syndrome

Patients who rupture an endometriotic cyst may present with an acute abdomen as a
medical emergency.
Occasionally pain may also occur in other regions. Cysts can occur in the bladder
(although rare) and cause pain and even bleeding during urination. Endometriosis can
invade the intestine and cause painful bowel movements or diarrhea.

In addition to pain during menstruation, the pain of endometriosis can occur at other
times of the month and doesn't have to be just on the date on menses. There can be
pain with ovulation, pain associated with adhesions, pain caused by inflammation in the
pelvic cavity, pain during bowel movements and urination, during general bodily
movement i.e. exercise, pain from standing or walking, and pain with intercourse. But
the most desperate pain is usually with menstruation and many women dread having
their periods. Also the pain can start a week before menses, during and even a week
after menses, or it can be constant. There is no known cure for endometriosis.

6auses

While the exact cause of endometriosis remains unknown, many theories have been
presented to better understand and explain its development. These concepts do not
necessarily exclude each other.

1. Estrogens: Endometriosis is a condition that is estrogen-dependent and thus

seen primarily during the reproductive years. In experimental models, estrogen is
necessary to induce or maintain endometriosis. gedical therapy is often aimed at
lowering estrogen levels to control the disease. Additionally, the current research
into aromatase, an estrogen-synthesizing enzyme, has provided evidence as to
why and how the disease persists after menopause and hysterectomy.
2. Retrograde menstruation: The theory of retrograde menstruation, first proposed
by John A. Sampson, suggests that during a woman's menstrual flow, some of
the endometrial debris exits the uterus through the fallopian tubes and attaches
itself to the peritoneal surface (the lining of the abdominal cavity) where it can
proceed to invade the tissue as endometriosis. While most women may have
some retrograde menstrual flow, typically their immune system is able to clear
the debris and prevent implantation and growth of cells from this occurrence.
However, in some patients, endometrial tissue transplanted by retrograde
menstruation may be able to implant and establish itself as endometriosis.
Factors that might cause the tissue to grow in some women but not in others
need to be studied, and some of the possible causes below may provide some
explanation, p
, hereditary factors, toxins, or a compromised immune system. It
can be argued that the uninterrupted occurrence of regular menstruation month
after month for decades is a modern phenomenon, as in the past women had
more frequent menstrual rest due to pregnancy and lactation. Sampson's theory
certainly is not able to explain all instances of endometriosis, and it needs
additional factors such as genetic or immune differences to account for the fact
that many women with retrograde menstruation do not have endometriosis. In
addition, at least one study found that endometriotic lesions are biochemically
very different from transplanted ectopic tissue, which casts doubt on Sampson's
theory.
d. g llerianosis: A competing theory states that cells with the potential to become
endometrial are laid down in tracts during embryonic development and
organogenesis. These tracts follow the female reproductive (gullerian) tract as it
migrates caudally (downward) at 8±10 weeks of embryonic life. Primitive
endometrial cells become dislocated from the migrating uterus and act like seeds
or stem cells. This theory is supported by foetal autopsy.
4. 6oelomic getaplasia: This theory is based on the fact that coelomic epithelium
is the common ancestor of endometrial and peritoneal cells and hypothesizes
that later metaplasia (transformation) from one type of cell to the other is
possible, perhaps triggered by inflammation. This theory is further supported by
laboratory observation of this transformation.
5. Genetics: Hereditary factors play a role. It is well recognized that daughters or
sisters of patients with endometriosis are at higher risk of developing
endometriosis themselves; for example, low progesterone levels may be genetic,
and may contribute to a hormone imbalance. There is an about 10-fold increased
incidence in women with an affected first-degree relative. A 2005 study published
in the - p
 
pp found a link between endometriosis
and chromosome 10q26. One study found that in female siblings of patients with
endometriosis the relative risk of endometriosis is 5.7:1 versus a control
population.
6. •ransplantation: It is accepted that in specific patients endometriosis can
spread directly. Thus endometriosis has been found in abdominal incisional scars
after surgery for endometriosis. It can also grow invasively into different tissue
layers,  p , from the cul-de-sac into the vagina. On rare occasions endometriosis
may be transplanted by blood or by the lymphatic system into peripheral organs
such as the lungs and brain.
7. ~mmune system: Research is focusing on the possibility that the immune system
may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In
this context there is interest in studying the relationship of endometriosis to
autoimmune disease, allergic reactions, and the impact of toxins. It is still unclear
what, if any, causal relationship exists between toxins, autoimmune disease, and
endometriosis.
8. Environment: There is a growing suspicion that environmental factors may
cause endometriosis, specifically some plastics and cooking with certain types of
plastic containers with microwave ovens. Other sources suggest that pesticides
and hormones in our food cause a hormone imbalance.
9. Birth Defect: In rare cases where imperforate hymen does not resolve itself prior
to the first menstrual cycle and goes undetected, blood and endometrium are
trapped within the uterus of the patient until such time as the problem is resolved
by surgical incision. gany health care practitioners never encounter this defect,
and due to the flu-like symptoms it is often misdiagnosed or overlooked until
multiple menstrual cycles have passed. By the time a correct diagnosis has been
made, endometrium and other fluids have filled the uterus and fallopian tubes
with results similar to retrograde menstruation resulting in endometriosis. The
initial stage of endometriosis may vary based on the time elapsed between onset
and surgical procedure.
6ause of pain

The way endometriosis causes pain is the subject of much research. Because many
women with endometriosis feel pain during or around their periods and may spill further
menstrual flow into the pelvis with each menstruation, some researchers are trying to
reduce menstrual events in patients with endometriosis.

Endometriosis lesions react to hormonal stimulation and may "bleed" at the time of
menstruation. The blood accumulates locally, causes swelling, and triggers
inflammatory responses with the activation of cytokines. It is thought that this process
may cause pain.

Pain can also occur from adhesions (internal scar tissue) binding internal organs to
each other, causing organ dislocation. Fallopian tubes, ovaries, the uterus, the bowels,
and the bladder can be bound together in ways that are painful on a daily basis, not just
during menstrual periods.

Smoking

This condition is associated with tobacco smoking in women. The risk of a cyst turning
to be ovarian cancer is extremely high in such conditions especially in women in their
d0's. Ovarian cysts may indicate advanced endometriosis and often is associated with
reduced fertility or infertility. Smoking causes decreased estrogens with breakthrough
bleeding and shortened luteal phases. Smokers have an earlier than normal (by about
1.5-d years) menopause which suggests that there is some toxic effect of smoking on
the follicles directly. Chemically, nicotine has been shown to concentrate in cervical
mucous and metabolites have been found in follicular fluid and been associated with
delayed follicular growth and maturation. Finally, there is some affect on tubal motility
because smoking is associated with an increased incidence of ectopic pregnancy as
well as an increased spontaneous abortion rate.

Pregnancy

Aging brings with it many effects that may reduce fertility. Depletion over time of ovarian
follicles affects menstrual regularity. Endometriosis has more time to produce scarring
of the ovary and tubes so they cannot move freely or it can even replace ovarian
follicular tissue if ovarian endometriosis persists and grows. Leiomyomata (fibroids) can
slowly grow and start causing endometrial bleeding that disrupts implantation sites or
distorts the endometrial cavity which affects carrying a pregnancy in the very early
stages. Abdominal adhesions from other intraabdominal surgery, or ruptured ovarian
cysts can also affect tubal motility needed to sweep the ovary and gather an ovulated
follicle (egg).

Endometriosis in postmenopausal women does occur and has been described as an

aggressive form of this disease characterized by complete progesterone resistance and
extraordinarily high levels of aromatase expression. In less common cases, girls may
have endometriosis symptoms before they even reach menarche.

Pathophysiology
Active endometriosis produces inflammatory mediators that cause pain and
inflammation, as well as scarring or fibrosis of surrounding tissue. Triggers of various
kinds, including menses, toxins, and immune factors, may be necessary to start this
process. Typical endometriotic lesions show histologic features similar to endometrium,
namely endometrial stroma, endometrial epithelium, and glands that respond to
hormonal stimuli. Older lesions may display no glands but hemosiderin deposits as
residual. To the eye, lesions can appear dark blue or powder-burn black and vary in
size; red, white, yellow, brown or non-pigmented. Some lesions within the pelvis walls
may not be visible to the eye, as normal-appearing peritoneum of infertile women
reveals endometriosis on biopsy in 6±1d of cases. Additionally other lesions may be
present, notably endometriomas of the ovary, scar formation, and peritoneal defects or
pockets. Endometrioma on the ovary of any significant size (Approx. 2 cm +) must be
removed surgically because hormonal treatment alone will not remove the full
endometrioma cyst, which can progress to acute pain from the rupturing of the cyst and
internal bleeding. Endometrioma is sometimes misdiagnosed as ovarian cysts.

Endometrial cells in women with endometriosis demonstrate increased adherence to

peritoneal cells and increased expression of splice variants of CD44, a cell-surface
protein involved in cell adhesions. Early endometriosis typically occurs on the surfaces
of organs in the pelvic and intra-abdominal areas. Health care providers may call areas
of endometriosis by different names, such as implants, lesions, or nodules. Larger
lesions may be seen within the ovaries as endometriomas or "chocolate cysts",
"chocolate" because they contain a thick brownish fluid, mostly old blood. Endometriosis
may trigger inflammatory responses leading to scar formation and adhesions.

gost endometriosis is found on these structures in the pelvic cavity where it can
produce mild, moderate, and/or severe pain felt in the pelvis and/or lower back areas.
The pain is often more severe before, during, and/or after the menstrual period:

0 Ovaries (the most common site)

0 Fallopian tubes
0 The back of the uterus and the posterior cul-de-sac
0 The front of the uterus and the anterior cul-de-sac
0 Uterine ligaments such as the broad or round ligament of the uterus
0 Pelvic and back wall
0 Intestines, most commonly the rectosigmoid
0 Urinary bladder and ureters

Bowel endometriosis affects approximately 10 of women with endometriosis, and can

cause severe pain with bowel movements.
Endometriosis may spread to the cervix and vagina or to sites of a surgical abdominal
incision.

Less commonly lesions can be found on the diaphragm. Diaphragmatic endometriosis is

rare, most always on the right hemidiaphragm, and may inflict cyclic pain of the right
shoulder just before and during menses. Rarely, endometriosis can be extraperitoneal
and is found in the lungs and CNS.

Pleural implantations are associated with recurrent right pneumothoraces at times of

menses, termed catamenial pneumothorax.

Endometriosis may also present with skin lesions in cutaneous endometriosis.

6omplications
Complications of endometriosis include:

0 Internal scarring
0 Adhesions
0 Pelvic cysts
0 Chocolate cyst of ovarys
0 Ruptured cyst
0 Blocked bowel/bowel obstruction

Infertility can be related to scar formation and anatomical distortions due to the
endometriosis; however, endometriosis may also interfere in more subtle ways:
cytokines and other chemical agents may be released that interfere with reproduction.

Complications of endometriosis include bowel and ureteral obstruction resulting from

pelvic adhesions. Also, peritonitis from bowel perforation can occur.

Endoscopic image of endometriotic lesions at the peritoneum of the pelvic wall.

 Endoscopic image of endometriotic lesions in the Pouch of Douglas and on the right sacrouterine
ligament.

Endoscopic image of a ruptured   p in left ovary.

•reatments
While there is no cure for endometriosis, in many patients menopause (natural or
surgical) will abate the process. In patients in the reproductive years, endometriosis is
merely managed: the goal is to provide pain relief, to restrict progression of the process,
and to restore or preserve fertility where needed. In younger women with unfulfilled
reproductive potential, surgical treatment attempts to remove endometrial tissue and
preserving the ovaries without damaging normal tissue. In women who do not have
need to maintain their reproductive potential, hysterectomy and/or removal of the
ovaries may be an option; however, this will not guarantee that the endometriosis and/or
the symptoms of endometriosis will not come back, and surgery may induce adhesions
which can lead to complications.
In general, the diagnose of endometriosis is confirmed during surgery, at which time
ablative steps can be taken. Further steps depend on circumstances: patients without
infertility can be managed with hormonal medication that suppress the natural cycle and
pain medication, while infertile patients may be treated expectantly after surgery, with
fertility medication, or with IVF.

Sonography is a method to monitor recurrence of endometriomas during treatments.

Treatments for endometriosis in women who do not wish to become pregnant include:

‰ormonal medication

0 Progesterone or Progestins: Progesterone counteracts estrogen and inhibits the

growth of the endometrium. Such therapy can reduce or eliminate menstruation
in a controlled and reversible fashion. Progestins are chemical variants of natural
progesterone.
0 Avoiding products with xenoestrogens, which have a similar effect to naturally
produced estrogen and can increase growth of the endometrium.
0 Hormone contraception therapy: Oral contraceptives reduce the menstrual pain
associated with endometriosis. They may function by reducing or eliminating
menstrual flow and providing estrogen support. Typically, it is a long-term
approach. Recently Seasonale was FDA approved to reduce periods to 4 per
year. Other OCPs have however been used like this off label for years.
Continuous hormonal contraception consists of the use of combined oral
contraceptive pills without the use of placebo pills, or the use of NuvaRing or the
contraceptive patch without the break week. This eliminates monthly bleeding
episodes.
0 Danazol (Danocrine) and gestrinone are suppressive steroids with some
androgenic activity. Both agents inhibit the growth of endometriosis but their use
remains limited as they may cause hirsutism and voice changes.
0 Gonadotropin Releasing Hormone (GnRH) agonist: These agents work by
increasing the levels of GnRH. Consistent stimulation of the GnRH receptors
results in downregulation, inducing a profound hypoestrogenism by decreasing
FSH and LH levels. While effective in some patients, they induce unpleasant
menopausal symptoms, and over time may lead to osteoporosis. To counteract
such side effects some estrogen may have to be given back (add-back therapy).
These drugs can only be used for six months at a time.
| Lupron depo shot is a GnRH agonist and is used to lower the hormone
levels in the woman's body to prevent or reduce growth of endometriosis.
The injection is given in 2 different doses a once a month for d month shot
with the dosage of (11.25 mg) or a once a month for 6 month shot with the
dosage of (d.75 mg).
0 Aromatase inhibitors are medications that block the formation of estrogen and
have become of interest for researchers who are treating endometriosis.
Other medication

0 NSAIDs Anti-inflammatory. They are commonly used in conjunction with other

therapy. For more severe cases narcotic prescription drugs may be used. NSAID
injections can be helpful for severe pain or if stomach pain prevents oral NSAID
use.
0 gST gorphine sulphate tablets and other opioid painkillers work by mimicking
the action of naturally occurring pain-reducing chemicals called "endorphins".
There are different long acting and short acting medications that can be used
alone or in combination to provide appropriate pain control.
0 Diclofenac in suppository or pill form. Taken to reduce inflammation and as an
analgesic reducing pain.

Surgery

Procedures are classified as

0 conservative when reproductive organs are retained,

0 semi-conservative when ovarian function is allowed to continue, and
0 radical when the uterus and ovaries are removed.

Conservative therapy consists of removal, excision or ablation of endometriosis,

adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as
much as is possible.

Radical therapy in endometriosis removes the uterus (hysterectomy) and tubes and
ovaries (bilateral salpingo-oophorectomy) and thus the chance for reproduction. Radical
surgery is generally reserved for women with chronic pelvic pain that is disabling and
treatment-resistant. Not all patients with radical surgery will become pain-free.

Semi-conservative therapy preserves a healthy appearing ovary, and yet, it also

increases the risk of recurrence.

For patients with extreme pain, a presacral neurectomy may be indicated where the
nerves to the uterus are cut. However, strong clinical evidence showed that presacral
neurectomy is more effective in pain relief if the pelvic pain is midline concentrated, and
not as effective if the pain extends to the left and right lower quadrants of the
abdomen.[4] This is due to the fact that the nerves to be transected in the procedure are
innervating the central or the midline region in the female pelvis. Furthermore, women
who had presacral neurectomy have higher prevalence of chronic constipation not
responding well to medication treatment because of the potential injury to the
parasympathetic nerve in the vicinity during the procedure.