New Understanding of Endometriosis Offers Hope for New Treatments

Jun 6

Endometriosis: A Local and Systemic Disease

Endometriosis is now understood to be both a pelvic disease, as well as a systemic (body-wide) disease. About 10-15% of women suffer from endometriosis, and 85% of women with chronic pelvic pain are eventually found to have endometriosis.

Endometriosis occurs when the tissue normally confined to the inside of the uterus (endometrium) grows outside the uterus. It can implant anywhere in the body, from the pelvis and abdomen all the way to the lungs and surgical scars.

Endometriosis in the pelvis causes varying degrees of pelvic pain and abnormal bleeding. Distant endometriosis can cause symptoms related to that organ. For example, women with endometriosis in the lungs can cough up blood every time they have a period.

The presence of endometriosis anywhere in the body can set up a chronic state of inflammation, due to over-production of inflammatory molecules called cytokines and interleukins. This can lead to a sensation of chronic fatigue or feeling unwell.

Endometriosis implants possess abnormal hormone production

Normal endometrium (the tissue lining the uterus) grows and sheds in response to ovarian hormones. It does not have its own independent source of hormone production.

Endometriosis is a disorder of estrogen production on a cellular level.

In women with endometriosis, the processing of estrogen is abnormal, both within the cells lining the uterus (the endometrium), and in endometriosis implants outside the uterus.

Evolution of the understanding of endometriosis offers hope for new treatments such as estrogen blockers and progesterone blockers.

Endometriosis implants have an abnormal amount of an enzyme called “aromatase”. This enzyme converts estrogen-precursor molecules to estrogen. Endometriosis implants also have high levels of estrogen receptors. Therefore endometriosis implants can both synthesize estrogen independent of the ovarian hormones; and they are more sensitive to estrogen.

Endometriosis implants are thus “self-perpetuating”. Endometriosis located outside the uterus can re-generate itself and spread through self-stimulation, whether or not the uterus and ovaries are present. This explains why some women who have hysterectomy for endometriosis have recurrent pain after total hysterectomy. Hysterectomy and oophorectomy (removal of ovaries) “debulks” endometriosis tissue present in the uterus and ovaries, but it does not remove endometriosis implants present outside the uterus.

Endometriosis implants outside the uterus and the endometrium produce high levels of inflammatory chemicals called “cytokines” and “prostaglandins”. By releasing prostaglandins and cytokines, molecules responsible for cramping during normal periods, endometriosis can inflame the nearby tissues and nerves, resulting in chronic pain at any time of the menstrual cycle.

“Location, Location, Location”: Endometriosis Symptoms Depend on Location

Location of endometriosis implants is key to their symptoms and other clinical manifestations.

Pelvic endometriosis is usually found in three places:

the tissue lining the pelvis and ligaments that support the uterus (pelvic peritoneum), uterosacral ligaments — ligaments that support the uterus in the pelvis, and pelvic nerves. Endometriosis that gets into the pelvic nerve fibers can radiate pain to the back, legs, and other parts of the body.
the ovary (a collection of endometriosis cells and fluid called an “endometrioma”)
in the wall between the vagina and rectum (recto-vaginal septum)

Although these are the common locations of endometriosis, it can occur almost anywhere in the body.

Systemic Endometriosis: Endometriosis in the intestines can cause irritable bowel symptoms and intestinal bleeding. Endometriosis in the lungs can cause hemoptysis (coughing up blood) during menses. Endometriosis in surgical scars can cause cyclic pain and swelling in those scars.

The location of endometriosis implants sometimes explains why some people with minimal endometriosis can have a lot of pain; while others with large cystic endometriosis can have no pain. For example, you can have a few small endometriosis implants on or near the pelvic nerves and have a great deal of pain; while another person can have a large cyst of endometriosis on the ovary and have no pain. The ovary has a different nerve supply and can apparently “tolerate” bulkier endometriosis.

Endometriosis that grows on and into the pelvic nerves can cause referred pain anywhere along the path the nerve innervates. For example, endometriosis on or near the obturator nerve, which supplies the inner thigh, can cause pain down the leg, and even in the groin/labial area. Endometriosis along the pudendal nerve, which innervates the lower vagina and external female genitalia, can cause pain anywhere along that nerve’s distribution.

Endometriosis in the ligaments supporting the uterus can be particularly troublesome because it can infiltrate the pelvic nerves, in close proximity.

Traditional Treatment for Endometriosis Focused on Suppressing the Growth of Endometriosis Implants

The main-stays of endometriosis treatment have been:

suppression of menses with progesterone
use of anti-inflammatory medications (e.g. ibuprofen) to reduce pain
laparoscopic removal of endometriosis implants
Use of Lupron (suppresses ovarian hormone production) to create a short-term “menopause” and withdraw hormonal support to endometriosis implants
removal of uterus, tubes, and ovaries (total hysterectomy with bilateral salpingoophorectomy)

While each of these has their place in treating endometriosis, none of these is completely effective at eradicating endometriosis.

In fact, endometriosis is now seen as a chronic systemic disease. The goal of endometriosis treatment should be to control manifestation and progression of the disease, preferably without resorting to the extreme of hysterectomy, at least until childbearing is completed.