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Endometriosis – An Overview

by - 02.08.2017 | Endometriosis, Infertility

What is it?

Endometriosis is an estrogen-dependent disease characterized by the presence of endometrial tissue located outside of the uterus. It has been estimated to affect up to 10% of reproductive aged women and as high as 25-50% of women with pelvic pain and/or unexplained infertility1,2. Endometrial implants can range from 1 mm superficial peritoneal lesions to ovarian lesions as large as 10 cm in size, often requiring surgical resection. Because its growth is dependent on ovarian produced steroids, namely estrogen, it mainly affects women in their reproductive years, most severely 25-35 years old3. This is also why the lesions undergo cycles of growth and bleeding in tandem with the normal endometrium of a menstrual cycle.

Factors that have been shown to increase the risk of endometriosis include having a genital outlet obstruction (such as cervical stenosis), early menarche, a menstrual cycle length of fewer than 26 days, menstrual bleeding for longer than 7 days per cycle, or a first degree relative affected by severe disease4.

What causes it?

There are several leading theories on the pathogenesis of endometriosis including retrograde menstruation, coelomic metaplasia, and altered immunity. Newer research is also proposing stem cells and genetic origins of the disease.  The problem is that no one theory can explain the wide range of locations that endometriotic lesions are found, which means the disease etiology is very likely multifactorial. The most well accepted theory, retrograde menstruation, was proposed by Sampson in the 1920’s and states that endometrial tissue is transported in a retrograde fashion through patent fallopian tubes into the peritoneal cavity 5,6. The ectopic cells then establish a blood supply, proliferate and produce endometrial implants. Another theory, coelomic metaplasia, argues that abdominal-pelvic peritoneum contains undifferentiated cells that can differentiate into endometrial cells 7. Numerous studies indicate that in women with endometriosis, the pelvic peritoneal environment is immunologically abnormal, with increased concentrations of white blood cells, cytokines (products of inflammation), and growth factors 8. This altered immunity would help explain why some women with retrograde menstruation have difficulty clearing the refluxed cells causing endometriosis, while others do not.

In addition to the traditional theories described above, newer research is showing that stem cells may also play a role in the etiology, especially when it occurs in distant sites like the lung or brain. Studies have shown that de-novo development of endometrial cells can occur from both stem cells in the uterine endometrium as well as the bone-marrow 9,10.

Regardless of which theory may be correct, what we do know is that once implanted, estrogen impacts its growth. This is likely the reason why the disease has developed a way to make its own estrogen: expression of the enzyme aromatase, normally found in ovaries or fatty tissue, which converts androgens (such as testosterone) to estrogens 2. In simpler words, this means that the disease can make its own food even if ovarian production of estrogen is limited, making it a difficult disease to treat!

What are the symptoms?

Endometriosis typically presents with symptoms of pelvic pain or infertility, secondary to an inflammatory response triggered by lesion growth or bleeding. The most common presenting symptoms include cyclical pain prior to the menstrual cycle, pain with intercourse, and chronic pelvic pain 11. Occasionally, the pain is associated with the site of lesion (such as an implant on the back of the vaginal vault causing pain with intercourse). The difficulty, however, is that the complaint of pain is often non-specific. Chronic pelvic pain (pain below the umbilicus for more than 6 months) is a common gynecologic problem, affecting as many as 3.8% of patients who present to their primary physician12. Other common gynecologic causes of chronic pelvic pain include chronic pelvic inflammatory disease, adenomyosis, and uterine fibroids. Non-gynecologic diseases such as irritable bowel syndrome, painful bladder syndrome, and fibromyalgia, can also contribute to the pelvic pain.

Infertility, the failure to conceive after 12 months of regular unprotected intercourse in women under 35 years of age or 6 months in woman over 35 years, is another possible outcome of endometriosis. The prevalence of endometriosis increases to as high as 25%-50% in women with infertility, while 30-50% of women with endometriosis have infertility. The probability of achieving a live birth per menstrual cycle in women with untreated endometriosis is estimated to be anywhere from 2% to 10%, compared to 20% of normal reproductive age couples without infertility13,14. There have been multiple mechanisms proposed. Severe endometriosis can lead to the formation of pelvic adhesions (scar tissue) which can distort or obstruct the normal pelvic anatomy, impairing oocyte release or transport to the fallopian tube.  Though in the absence of mechanical obstruction, such as in mild-moderate forms of the disease, infertility is still common. Inflammation can impair oocyte production and ovulation in the affected ovary of endometriomas, damage oocytes and sperm, have toxic effects on the embryo, and impair transport through the fallopian tube 15-17. In addition to the inflammatory effects, there is increasing evidence that implants in the pelvis can negatively impact the normal endometrium and lead to implantation failure 18.

How can it be diagnosed?

Despite endometriosis being a common disorder, it remains remarkably difficult to diagnose. The current gold standard for the diagnosis of endometriosis is surgical visualization of endometriosis lesions, usually by laparoscopy (minimally invasive surgery). Because of the invasive nature of surgery, many women with endometriosis experience their symptoms for years before being diagnosed. To improve screening for endometriosis and avoid missing diagnoses, many gynecologists use a combination of clinical history, examination, and non-invasive testing.

Although in most women with endometriosis the physical examination is normal, certain findings can suggest the presence of endometriosis. Similarly, although some imaging (such as ultrasound and MRI) is sensitive at detecting lesions like endometriomas (ovarian cysts with hemorrhagic content from endometriosis, classically called “chocolate filled cysts”), no modality has proven to be an effective diagnostic tool regardless of disease severity. Imaging and physical exam can, however, be useful in ruling out other causes of pelvic pain, along with laboratory studies to rule out infectious causes.

Given the difficulty in accurately diagnosing endometriosis without surgery, it is important to always visit a specialist when concerned for endometriosis so you can be screened, diagnosed, and have your symptoms treated as soon as possible. For treatment strategies, please read the additional blogs on medical and surgical treatment of endometriosis.


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