Endometriosis is a chronic, inflammatory disease in women of reproductive age, in which the uterine endometrial cells and tissues form outside the uterus. It is a leading cause of pelvic pain and infertility in women of childbearing age and can be challenging to treat.
Some physicians suggest¹ that endometrial problems arise from genes that cause retrograde (flowing backward) menstruation, which results in endometrial tissue flowing back through the fallopian tubes and depositing in the abdomen lining (peritoneum).
Other medical doctors think this is not the case. Instead, they attribute endometriosis to a combination of:
Deposits of endometrial cells are controlled by the same hormones that govern the menstrual cycle. Therefore, their bleeding and associated pain happen cyclically.
In rare cases, endometrial cells are present in locations far from the uterus as the brain. Endometriosis is usually found in the pelvic area and nearby organs.
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There are three main observable physical characteristics of endometriosis. These are superficial peritoneal lesions, ovarian endometriomas, and deep infiltrating endometriosis.
There is an associated disease called adenomyosis — in which the endometrial cells infiltrate the muscle layer of the uterus. It is often associated with endometriosis. However, the pain it causes is independent of endometriosis.
Pelvic pain is a common symptom of endometriosis. Although, in and of itself, it is not a reliable indicator of the disease as the pain can stem from a range of gynecological or abdominal problems. In addition, endometriosis-related pelvic pain is cyclic, chronic, and progressive. People with endometriosis may have painful urination, constipation, and pain during sex.
Infertility is often associated with endometriosis, although you can still have endometriosis without being infertile. The disease causes infertility through adhesions and scarring that alter normal pelvic anatomy. In addition, the inflammatory environment that arises from endometriosis lesions makes conception less likely. These cells produce inflammatory biological markers that form a fluid that produces a hostile environment where sperm and eggs cannot survive, let alone fertilize and implant.
Three main methods of managing endometriosis exist. These include medical treatments, surgery, and assisted reproductive techniques (ART).
Treatment can either be non-hormonal or hormonal.
Non-hormonal treatments include non-steroidal anti-inflammatory drugs (NSAIDs).
Hormonal treatments may include combined oral contraceptives (COCs), progestins, and gonadotropin-releasing hormone analogs (GnRHa). Some hormonal therapies stop your period, which helps deal with endometriosis by keeping inflammation at bay — two major causes of pain and infertility.
Surgery for endometriosis is either conservative or definitive.
Conservative surgery is usually a laparoscopy (a keyhole surgery that uses a camera to inspect and operate on organs inside the abdomen and pelvic area). It involves removing lesions (either entirely or partially).
Definitive surgery is the removal of lesions and the uterus (hysterectomy).
In some cases, one or both ovaries are removed (oophorectomy).
Recurrence of endometriosis after surgery is common, and outcomes vary significantly among different studies².
Assisted reproductive techniques
Reproductive technologies like in-vitro fertilization (IVF) are typically used when neither medical nor surgical interventions have helped. According to a recent clinical review, IVF represents one of the key treatment options for patients who have endometriosis-associated infertility, “especially when it involves a compromised tubal function, aberrant peritoneal anatomy, or failure of other treatment methods.”³
From the 1970s onwards, experts have attempted to classify and stage endometriosis to understand it better and improve health outcomes.
The process of defining endometriosis stages has been through many iterations over the years, leading to two generally accepted classification systems⁴: the Revised American Society for Reproductive Medicine score (rASRM) and the EndoFound classification system.
A third scoring system developed in 2010 — Endometriosis Fertility Index (EFI) — is used as a fertility prognostic. The EFI is generally used to determine the best candidates for IVF treatment.
There are four stages of endometriosis, based on the rASRM, that are assigned based on scores derived from the location of the endometriosis (peritoneum, ovaries, and fallopian tubes) as well as the depth and the size of the lesions. The rASRM is mainly used for surgical and outcome planning.
What is stage I?
(1-5 points - Minimal) Stage I endometriosis lesions are small, few in number, and don’t penetrate deeply into the surrounding tissue. There is little to no scar tissue present.
What is stage II?
(6-15 points - Mild) Stage II lesions are greater in number and penetrate slightly more deeply than those found in stage I. There may be some scar tissue present.
What is stage III?
(16-40 points - Moderate) At stage III, lesions are deep and numerous. They also may appear in at least one ovary as “chocolate cysts,”⁵ which are endometrial cysts that excrete blood and tissue. The blood oxidizes and turns brown, hence the name. Adhesions (scar tissue) may also form between organs causing them to stick together.
What is stage IV?
(>40 points - Severe) At this stage, there are large “chocolate cysts” on at least one ovary, many deep lesions, and adhesions throughout the whole pelvic cavity.
Some limitations exist with this system: it does not provide prognostic information, does not consider associated infertility, and does not describe the pain and intense, debilitating nature of endometriosis. For example, according to the above classification, you could have stage I endometriosis yet still have unbearable pain and significant negative impacts on your life.
To supplement the rASRM system, the Endometriosis Foundation of America⁶ devised a category system.
In this category, peritoneal endometriosis is minimal, and endometrial cells are located on the thin membrane that lines the abdomen.
Here, ovarian endometriomas or the aforementioned “chocolate cysts” are in the ovaries.
Deep infiltrating endometriosis I (DIE I) involves pelvic organs such as the ovaries, rectum, and uterus. It can also lead to “frozen pelvis,” where the adhesions are so significant that pelvic structures are fused and essentially “frozen” in the incorrect locations.
Deep infiltrating endometriosis II (DIE II) is more severe and involves organs both inside and outside the pelvis (such as the bowels, appendix, diaphragm) and even above the diaphragm (heart, lungs, and brain).
There is growing support for a fifth category (category V), which would describe diffuse endometriosis involving multiple distanced organs with significant adhesions presenting difficulties for surgery and impaired fertility.
Endometriosis is diagnosed and staged through surgery and confirmation of endometrial tissue outside the uterus.
Unfortunately, using the presence or absence of lesions found through surgery as a primary diagnostic tool means that, on average, it takes someone with endometriosis between 4-11 years¹ to be diagnosed.
There is hope that a less invasive diagnostic method will become standard over surgery and imaging — using the patient's symptoms and affected areas as indicators.
Emerging technology is working to advance the use of bloodwork to find endometriosis biomarkers⁷.
For now, staging of endometriosis is done with exploratory surgery and imaging.
Transvaginal sonography (TVS)
Sonography is usually the first step to a diagnosis of endometriosis for various reasons. It is readily available, provides immediate results, is minimally invasive, and allows for dynamic imaging where pelvic structures can be moved and imaged to confirm or deny the presence of adhesions and “frozen pelvis.”
In addition, TVS also has high sensitivity and specificity, which means it is very good at detecting endometriosis.
Magnetic resonance imaging (MRI)
This is a good diagnostic tool for determining the size and location of lesions and planning the surgery to remove them. It is accurate and reproducible. However, it is more expensive and less available than ultrasound.
The real limitation with diagnosing endometriosis and planning surgery comes not from the imaging techniques and tests but the lack of consensus on classification systems for their results. These classification systems need to achieve accurate descriptions of localization, depth, cell type, degree of pain, the extensiveness of adhesions, the effectiveness of surgery, and fertility.
The speed at which endometriosis progresses is not well understood, and more studies are needed to understand its course. However, in general, it is considered a chronic and progressive condition.
One study found that endometriosis resolved naturally in around 25% of women in 6-12 months if left untreated. In 25%, it remained unchanged, and in about 50% of cases, it continued to progress⁸ with enlarging growths and additional deposits.
Endometriosis is a debilitating condition thought to affect about 11% of American women. The prevalence may be higher¹ as it is difficult to reach a diagnosis. It is characterized by debilitating pelvic pain and infertility and can impact your mental health, employment, and intimate relationships.
Endometriosis needs to be further researched and better understood from a clinical perspective to provide comprehensive help to patients. In the meantime, treatments mainly consist of hormonal and non-hormonal medicines, surgery, and assistive reproductive technology for women who wish to conceive.
Endometriosis stages: Understanding the different stages of endometriosis | Endometriosis Foundation of America