What causes 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 as endometrial cells. (This process is termed coelomic metaplasia.)
It is also likely that direct transfer of endometrial tissues during 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, there is evidence that shows alternations 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.

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 painful sexual intercourse (dyspareunia) or cramping during intercourse, and or/pain during 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.
• Lastly, pain can result when endometriosis implants form scars. There is no relationship between severity of pain and how widespread the endometriosis is (the "stage" of endometriosis).

Endometriosis can be one of the reasons for infertility for otherwise healthy couples. When laparoscopic examinations are performed for infertility evaluations, endometrial implants can be found in some of these patients, many of whom may not have painful symptoms of endometriosis. The reasons for a decrease in fertility are not completely understood, but might be due to both anatomic and hormonal factors. The presence of endometriosis may involve masses of tissue or scarring (adhesions) within the pelvis that may distort normal anatomical structures, such as Fallopian tubes, which transport the eggs from the ovaries. Alternatively, endometriosis may affect fertility through the production of hormones and other substances that have a negative effect on ovulation, fertilization of the egg, and/or implantation of the embryo

Endometriosis and cancer risk

Women with endometriosis have an increased risk for development of certain types of cancer of the ovary, known as epithelial ovarian cancer (EOC), according to some research studies. This risk is 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 the endometriosis 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 nodules are 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 and abdomen, 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 belly with large-incision laparotomy or small-incision laparoscopy.
Laparoscopy is the most common surgical procedure for the diagnosis of endometriosis. Laparoscopy is a minor surgical procedure done under general anesthesia, or in some cases under local anesthesia. It is usually performed as an out-patient procedure (the patient going home the same day). Laparoscopy is performed by first inflating the abdomen with carbon dioxide through a small incision in the navel. A long, thin viewing instrument (laparoscope) is then inserted into the inflated abdominal cavity to inspect the abdomen and pelvis. Endometrial implants can then be directly seen.
During laparoscopy, biopsies (removal of tiny tissue samples for examination under a microscope) can also be performed for a diagnosis. Sometimes biopsies obtained during laparoscopy show endometriosis even though no endometrial implants are seen during laparoscopy.
Pelvic ultrasound and laparoscopy are also important in excluding malignancies (such as ovarian cancer) that can cause symptoms that mimic endometriosis symptoms.

How is endometriosis treated?

Endometriosis can be treated with medications and/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 as ibuprofen 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. However, they do decrease prostaglandin production, and prostaglandins are well-known to have a role in production of pain sensation. Because the diagnosis of endometriosis is only definite after a woman undergoes surgery, there will of course be many women who are suspected of having endometriosis based on the nature of their pelvic pain symptoms. In such a situation, NSAIDs are commonly used, such as naproxen or ibuprofen, are commonly used. If they work to control pain, no other procedures or medical treatments are needed. If they do not relieve the pain, additional evaluation and treatment generally occur.
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 periods stop, 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 are asked 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 (male pattern 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 inhibitors (for example, anastrozole [Arimidex] and letrozole [Femara]). These drugs act by interrupting local estrogen formation within the endometriosis implants themselves. They also inhibit estrogen production in the ovary, brain, and other sources, such as adipose tissue. Research is still ongoing to characterize the effectiveness of aromatase inhibitors in the management of endometriosis. Aromatase inhibitors cause significant bone loss with prolonged use and cannot be used alone without other medications such as GnRH agonists or combination of oral contraceptives in premenopausal women because they stimulate development of multiple follicles at ovulation.