Prof Dr Almahdy a Apt Endometriosisppt

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Endometriosis

Prof. Dr. Almahdy A, Apt

Fakultas Farmasi Unand.

2009



What is endometriosis?

Endometriosis is a common cause of chronicpelvic pain in women and is also associated

with infertility. Characterized by the presence

of endometrial tissue (Endometrial cells arethe same cells that are shed each month

during menstruation) outside the uterus,

endometriosis is a chronic, recurring disease.Therapy is targeted at relieving symptoms and

improving fertility.

http://www.medicinenet.com/script/main/art.asp?articlekey=92709




The cells of endometriosis attach

themselves to tissue outside the uterus

and are called endometriosis implants.

These implants are most commonlyfound on the ovaries, the Fallopian

tubes, outer surfaces of the uterus or

intestines, and on the surface lining of the pelvic cavity.



They can also be found in the vagina, cervix,

and bladder, although less commonly thanother locations in the pelvis. Rarely,

endometriosis implants can occur outside the

pelvis, on the liver, in old surgery scars, andeven in or around the lung or brain.

Endometrial implants, while they can cause

problems, are benign (not cancerous)

















Who is affected by endometriosis?

Endometriosis affects women in theirreproductive years. The exact prevalence of

endometriosis is not known, since many

women may have the condition and have nosymptoms. Endometriosis is estimated to

affect over one million women (estimates

range from 3% to 18% of women) in theUnited States. It is one of the leading causes

of pelvic pain and reasons for laparoscopic

surgery and hysterectomy in this country.










While most cases of endometriosis are diagnosed

in women aged around 25-35 years, endometriosis

has been reported in girls as young as 11 years of age. Endometriosis is rare in postmenopausal

women. Endometriosis is more commonly found in

white women as compared with African Americanand Asian women. Studies further suggest that

endometriosis is most common in taller, thin

women with a low body mass index (BMI).

Delaying pregnancy until an older age is also

believed to increase the risk of developing

endometriosis.



What causes endometriosis?

The cause of endometriosis is unknown. One theory is that

the endometrial tissue is deposited in unusual locations by

the backing up of menstrual flow into the Fallopian tubes

and the pelvic and abdominal cavity during menstruation(termed retrograde menstruation). The cause of

retrograde menstruation is not clearly understood. But

retrograde menstruation cannot be the sole cause of

endometriosis. Many women have retrograde

menstruation in varying degrees, yet not all of them

develop endometriosis.







Another possibility is that areas lining the pelvic

organs possess primitive cells that are able to

grow into other forms of tissue, such asendometrial cells. (This process is termed

coelomic metaplasia.)

It is also likely that direct transfer of endometrial tissuesduring surgery may be responsible for the endometriosis

implants sometimes seen in surgical scars (for example,

episiotomy or Cesarean section scars). Transfer of

endometrial cells via the bloodstream or lymphatic

system is the most likely explanation for the rare cases of

endometriosis that develop in the brain and other organs

distant from the pelvis.














Finally, some studies have shownalternations in the immune response in

women with endometriosis, which may

affect the body's natural ability to

recognize and destroy any misdirected

growth of endometrial tissue.







Normal Pelvic Structures



Endometriosis

http://www.gynsurgery.org/ols/uploads/endo_gen_typical2.jpg



Endometriosis

http://www.gynsurgery.org/ols/uploads/endo_deep_atyp1.jpg



Endometriosis




Endometriosis




Endometriosis

http://www.gynsurgery.org/ols/uploads/endo_typ_atyp3.jpg



Endometriosis





Endometriosis







What are endometriosis symptoms?

Most women who have endometriosis, in fact, do not have symptoms. Of those

who do experience symptoms, the common symptoms are pain (usually pelvic)

and infertility. Pelvic pain usually occurs during or just before menstruation and

lessens after menstruation.

Some women experience pain or cramping with intercourse, bowel movements

and/or urination. Even pelvic examination by a doctor can be painful. The pain

intensity can change from month to month, and vary greatly among women. Some

women experience progressive worsening of symptoms, while others can have

resolution of pain without treatment.

Pelvic pain in women with endometriosis depends partly on where the implants of

endometriosis are located. Deeper implants and implants in areas with many pain-

sensing nerves may be more likely to produce pain. The implants may also

produce substances that circulate in the bloodstream and cause pain.







Other symptoms related to endometriosis include:

lower abdominal pain,

diarrhea and/or constipation,

low back pain,

irregular or heavy menstrual bleeding, orblood in the urine.

Rare symptoms of endometriosis include chest pain or

coughing blood due to endometriosis in the lungs andheadache and/or seizures due to endometriosis in the

brain.





http://www.medicinenet.com/script/main/forum.asp?articlekey=24705












Endometriosis and cancer risk

Women with endometriosis have a mildly increased risk for

development of certain types of cancer of the ovary, known as

epithelial ovarian cancer (EOC). This risk seems to be highest in

women with endometriosis and primary infertility (those who have

never borne a child), but the use of oral contraceptive pills (OCPs),

which are sometimes used in the treatment of endometriosis,appears to significantly reduce this risk.

The reasons for the association between endometriosis and ovarian

epithelial cancer are not clearly understood. One theory is that theendometriosis implants themselves undergo transformation to

cancer. Another possibility is that the presence of endometriosis may

be related to other genetic or environmental factors that also

increase a women's risk of developing ovarian cancer















How is endometriosis diagnosed?

Endometriosis can be suspected based on

symptoms of pelvic pain and findings during

physical examinations in the doctor's office.

Occasionally, during a rectovaginal exam (one

finger in the vagina and one finger in the rectum),the doctor can feel nodules (endometrial implants)

behind the uterus and along the ligaments that

attach to the pelvic wall. At other times, no nodulesare felt, but the examination itself causes unusual

pain or discomfort.



Unfortunately, neither the symptoms nor the

physical examinations can be relied upon to

conclusively establish the diagnosis of endometriosis. Imaging studies, such as

ultrasound, can be helpful in ruling out other

pelvic diseases and may suggest the presence of

endometriosis in the vaginal and bladder areas,

but still cannot definitively diagnose

endometriosis. For an accurate diagnosis, a direct

visual inspection inside of the pelvis andabdomen, as well as tissue biopsy of the implants

are necessary.





As a result, the only accurate way of

diagnosing endometriosis is at the time

of surgery, either by opening the bellywith large-incision laparotomy or small-

incision laparoscopy.





How is endometriosis treated?

Endometriosis can be treated with medicationsand/or surgery. The goals of endometriosis

treatment may include pain relief and/or

enhancement of fertility.



Medical treatment of endometriosis

Nonsteroidal anti-inflammatory drugs or NSAIDs (such asibuprofen or naproxen sodium) are commonly prescribed

to help relieve pelvic pain and menstrual cramping. These

pain-relieving medications have no effect on the

endometrial implants.

Since endometriosis occurs during the reproductive years,

many of the available medical treatments for

endometriosis rely on interruption of the normal cyclical

hormone production by the ovaries. These medications

include GnRH analogs, oral contraceptive pills, and

progestins.















Gonadotropin-releasing hormone analogs

(GnRH analogs)

Gonadotropin-releasing hormone analogs

(GnRH analogs) have been effectively used to

relieve pain and reduce the size of

endometriosis implants. These drugs suppress

estrogen production by the ovaries by inhibiting

the secretion of regulatory hormones from the

pituitary gland. As a result, menstrual periodsstop, mimicking menopause. Nasal and injection

forms of GnRH agonists are available.











The side effects are a result of the lack of estrogen, and

include:

hot flashes, vaginal dryness, irregular vaginal bleeding,mood changes, fatigue, and loss of bone density

(osteoporosis).

Fortunately, by adding back small amounts of estrogen

and progesterone in pill form (similar to treatments

sometimes used for symptom relief in menopause) many

of the annoying side effects due to estrogen deficiency can

be avoided. "Add back therapy" is the term that refers to

this modern way of administering GnRH agonists along

with estrogen and progesterone in a way to keep the

treatment successful, but avoid most of the unwanted

side effects.













Oral contraceptive pills

Oral contraceptive pills (estrogen and progesterone in

combination) are also sometimes used to treat

endometriosis. The most common combination used is

in the form of the oral contraceptive pill (OCP).

Sometimes women who have severe menstrual pain areasked to take the OCP continuously, meaning skipping

the placebo (sugar pill) portion of the cycle. Continuous

use in this manner will free a woman of having any

menstrual periods at all. Occasionally, weight gain,breast tenderness, nausea, and irregular bleeding are

mild side effects. Oral contraceptive pills are usually

well-tolerated in women with endometriosis.















Progestins

Progestins [for example, medroxyprogesterone acetate (Provera,

Cycrin, Amen), norethindrone acetate, norgestrel acetate (Ovrette)]

are more potent than birth control pills and are recommended for

women who do not obtain pain relief from or cannot take a birth

control pill.

Side effects are more common and include:

breast tenderness, bloating, weight gain, irregular uterine

bleeding, and depression.

Since the absence of menstruation (amenorrhea) induced by high

doses of progestins can last many months after cessation of therapy,

these drugs are not recommended for women planning pregnancy.





















Other drugs used to treat endometriosis

Danazol (Danocrine)

Danazol (Danocrine) is a synthetic drug that

creates a high androgen (male type

hormone) and low estrogen hormonal

environment by interfering with ovulation

and ovarian production of estrogen. Eighty

percent of women who take this drug will

have pain relief and shrinkage of

endometriosis implants, but up to 75% of

women develop side effects from the drug.







Side effects can include:

weight gain, edema, decreased breast

size, acne, oily skin, hirsutism (malepattern hair growth), deepening of the

voice, headache, hot flashes, changes

in libido, and mood changes.











All of these changes are reversible,except for voice changes; but the

return to normal may take many

months. Danazol should not be

taken by women with certain types

of liver, kidney, and heart conditions



Aromatase inhibitors

A newer approach to the treatment of

endometriosis has involved the administration of drugs known as aromatase inhibi

tors [for example, anastrozole (Arimidex)

and letrozole (Femara)]. These drugs act byinterrupting local estrogen formation with

in the endometriosis implants themselves.

They also inhibit estrogen production in theovary, brain, and other sources, such as

adipose tissue.







Medical Treatment

Ovary EstrogenEndometriosis

TissueOral contraceptives

DanazolGnRH agonists

Progestin



Role of Estrogen in Endometriosis

Estrogen




Estrogen

Cell growth




Aromatase

Estrogen

Cell growth




Aromatase

Estrogen

Cell growth

PGE2

Cytokines



Aromatase In Endometriosis

•Aromatase is key for the biosynthesis of estrogen

• In patients aromatase expression is higher in

endometriosis tissue than in normalendometrium

• In endometriosis tissue aromatase activity is

stimulated by prostaglandin

• Estrogen synthesized by endometriotic tissue

stimulates growth of lesions




Aromatase

Estrogen

Cell growth

PGE2

Cytokines

Aromatase Inhibitors

• Letrozole

• Exemestane

• Anastrozole




Aromatase

Estrogen

Cell growth

PGE2

Cytokines

Aromatase Inhibitors

• Letrozole

• Exemestane

• Anastrozole

• Danazol



Research is still ongoing to characterize

the effectiveness of aromatase inhibitorsin the management of endometriosis.

Aromatase inhibitors cause significant

bone loss with prolonged use andcannot be used alone without other

medications in premenopausal women

because they stimulate development of

multiple follicles at ovulation



Endometriosis At A Glance

Endometriosis is the growth of endometrial tissue but in a location

outside of the uterus. Endometriosis is

most commonly found on other organs

of the pelvis.

The exact cause of endometriosis has not

been identified.



Endometriosis is more common in

women who are experiencing infertilitythan in fertile women, but the condition

does not fully prevent conception.

Pelvic pain during menstruation or

ovulation can be a symptom of

endometriosis, but may also occur in

normal women.



Endometriosis can be suspected by

definite diagnosis: by surgery,usually laparoscopy.

Treatment of endometriosis

includes medication and surgery for

both pain relief and treatment of infertility if pregnancy is desired.



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Prof Dr Almahdy a Apt Endometriosisppt