What are the causes of endometriosis?

In spite of the high prevalence of endometriosis in women all over the world, researchers have been unable to determine its exact cause.

A combination of genetic, biologic, and environmental factors appear to work together to trigger the initial process, to produce implantation, and to trigger subsequent reseeding and spreading of the implants.

Initial Cause and Distribution of Endometriosis

Retrograde Menstruation.

One favored explanation for the development of endometriosis implants involves retrograde menstruation.

This occurs when, during a woman's period, menstrual tissue flows backward through the fallopian tubes, rather than flowing out through the vagina.

Early theorists suggested that in some cases, the redistributed uterine tissue attached and grew in areas outside the uterus, forming endometriosis implants.

This theory does not fully explain endometriosis. Many women experience some retrograde menstruation, but not all of them develop endometrial cysts. Consequently, other factors must be at work to explain why uterine tissue becomes implanted and grows in areas outside the uterus.

Lymphatic Transport.

It has been suggested that endometriosis first develops when uterine tissue is separated and then is transported to other organs by way of the lymphatic system or the blood stream.

Causes of Persistence and Growth of Endometriosis

There are two basic mysteries surrounding the persistence and growth of endometriosis:

• Why do endometrial implants survive the attack by the immune system, which is typically launched against any foreign presence in the body?
  
• How do these endometrial implants develop new blood vessels and implant themselves in other locations?

Impaired Immune System.

Some research is focused on possible immune disorders in women with endometriosis.

One theory proposes that women with endometriosis have fewer natural killer (NK) cells, which are factors in the immune system important for surveillance. In their absence, the immune system is weakened and may allow endometrial tissue to invade and take root.

Another theory suggests that endometriosis represents an autoimmune condition, in which the immune system launches an attack on its own cells and tissue. Much of the evidence rests on the relatively high incidence of other inflammatory autoimmune disorders (e.g., multiple sclerosis, rheumatoid arthritis, lupus) that occur in women with endometriosis. It is unclear, however, how this response relates to endometriosis itself and whether endometriosis should be treated as an autoimmune condition.

Growth Factors and Angiogenesis.

Macrophages also produce growth factors, which are of particular interest because they play important roles in angiogenesis, a natural process by which new blood vessels form.

Vascular endothelial growth factor (VEGF) is secreted by endometrial cells, and so is of special interest. Under normal conditions, VEGF is secreted within the uterus. When oxygen levels drop following menstruation and blood loss, VEGF levels rise and promote the growth of new blood vessels. This process is important for repairing the uterus following menstruation.

When endometrial cells land outside the uterus, however, investigators theorize that this same process occurs with unfortunate results. The cells secrete VEGF when they are deprived of blood and oxygen, which in turn stimulates blood vessel growth. In this case, however, blood vessel growth serves to promote implantation outside the womb.

Other growth factors involved in angiogenesis that may play a role in endometriosis include transforming growth factors (such as TGF-beta), platelet-derived endothelial growth factor (PD-ECGF), and tumor necrosis growth factors.

Inflammatory Response.

The tissue damage, infertility, and pain produced by endometriosis may be due to an over-active response by the immune system to the early presence of endometrial implants. The body, perceiving the implants as hostile launches an attack.

Levels of large white blood cells called macrophages are elevated in endometriosis. Macrophages produce very potent factors, which include cytokines (particularly those known as interleukins) and prostaglandins. Such factors are known to produce inflammation and damage in tissues and cells.

Genetic Factors

A major study is underway to uncover the genetic factors that predispose certain women to endometriosis.

The incidence of endometriosis in women who have a mother or sister with the disorder may be up to 10 times higher than average.