Endometriosis — or endo, as it's commonly known — is a condition that affects around one in 10 people assigned female at birth. It happens when the tissue similar to the lining of the uterus grows outside of the uterus. This can cause chronic pain and heavy periods, and even affect fertility.

Unfortunately, thanks to a lack of research, many people with endometriosis go undiagnosed for years. Endo is an incredibly misunderstood condition, so we've put together a comprehensive explainer of the symptoms, possible causes, and treatments for endometriosis.

What is endometriosis?

Endometriosis is a chronic disease that happens when tissue similar to the lining of the uterus (endometrium) grows outside the uterus, such as the ovaries and fallopian tubes.

Although this tissue has some similarities with the lining of the uterus, it's not just a uterine or menstrual disease. It often appears as lesions, called implants, throughout the body and can affect nearly all organ systems. While it's commonly found in the pelvis and reproductive organs, it can also be found outside the pelvic cavity, which is known as extrapelvic endometriosis. Endometriosis can lead to adhesions, fibrosis, scar tissue and organ dysfunction due to its association with an inflammatory process.

It's estimated that around 10% of women and people with vaginas may have endometriosis, but the exact number is hard to tell due to the challenges involved in diagnosis. It's important to note that endometriosis can occur in fetuses, adolescents who haven't had their first period yet, people of reproductive age, and post-menopausal people. Interestingly, endometriosis has been documented in 17 cases in males.

Types of endometriosis 

Endometriosis is traditionally described as three major subtypes:

  • Superficial Peritoneal Endometriosis (SPE or SE): This type occurs when lesions form on the surface of tissue and organs, also called the peritoneum. The lesions can be black, bluish, red, white, clear, or a mix of colors. 
  • Deeply Infiltrating (DIE): This occurs when lesions, often like nodules, penetrate the surface of the peritoneum. Commonly affected areas include the uterosacral ligaments, round ligaments, rectum, rectovaginal space, retrocervical area, vagina, and bladder. 
  • Endometrioma (“Chocolate Cysts”) (OMA): These are cysts filled with old blood that contains inflammatory substances. The presence of an endometrioma can indicate deeply infiltrating disease is also present.

Rarely, endometriosis can be present in the abdominal wall, usually in scars of abdominal surgery; this is likely actual uterine tissue that has been misplaced during surgery.

Endometriosis symptoms 

The most common symptoms of endometriosis are:

Other symptoms may occur depending on the location of endometriosis; a few of these include sciatica when endometriosis affects pelvic nerves, lung collapses or coughing up blood when endometriosis is located in the thoracic cavity, and flank pain when kidneys are being impacted. 

As endometriosis infiltrates deeper and becomes more fibrotic, pain and symptoms can worsen and become chronic. Symptoms vary from each individual. Some patients may have debilitating periods, while others may not have any pain. This is one reason endometriosis can often be misdiagnosed or not diagnosed at all.

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What causes endometriosis?

What we know so far is that it's a complex disease that can show up in many different ways and different parts of the body. Interestingly, not all lesions are the same and they can behave differently in different individuals. Did you know that it can even occur in fetuses, adolescents, and people after menopause and hysterectomy? Shockingly, it has even been found in males! So, you can imagine how complicated and mysterious it can be.

The cause of endometriosis is not yet fully understood, but it's believed to be a combination of various factors from genetics to the immune system. There are several theories out there, and experts are still trying to figure out the exact cause. So, what are some of the theories? 

Retrograde menstruation

Retrograde menstruation theory suggests that menstrual blood flows backward from the uterus through the fallopian tubes and into the pelvis during the monthly menstrual period, leading to endometriosis.

This theory was first described in 1925 and is the most commonly cited one. It can explain why endometriosis is found on the ovaries and other parts of the pelvic cavity. However, there are some problems with this theory. For example, it doesn't explain why endometriosis is found in places far away from the pelvis, such as in fetuses and males. It also can't explain why endometriosis is different from the endometrium.

So while the implantation or retrograde menstruation theory is a widely accepted explanation for endometriosis, it has some limitations that need to be considered.

Embryological origin

The embryological origin theory suggests that endometriosis may be present from birth.

During early development, our organs form from three separate structures known as ducts. The reproductive tract starts forming from the Müllerian duct in all embryos. This theory proposes that tissue that becomes endometriosis may originate from this process, possibly failing to develop into the endometrium. This could explain why endometriosis has been observed in fetuses, males, and adolescents, alongside other abnormalities.

Several researchers have expanded on this theory, exploring additional possibilities related to the embryological development of endometriosis, such as coelomic metaplasia. Recent studies have found that endometriosis tissue may be older than endometrium tissue, indicating differences in epigenetic age

Stem cell theory

Stem cell theory suggests that stem cells from various sources, like the endometrium or bone marrow, can develop into endometriosis lesions, supporting both embryonic origin and retrograde menstruation theories.

When tissues are damaged, stem cells are recruited for repair, potentially leading to DNA mutations that contribute to endometriosis. Environmental factors, known as epigenetic modifications, may also play a role in these mutations.

Initially, it was believed that all lesions were clonal, originating from a single "parent" cell. However, recent advancements in biotechnology have shown that only some parts of lesions are clonal, while others may come from different cell lines. Further research is needed to fully understand this theory as technology progresses.

How is endometriosis diagnosed? 

Being diagnosed with endometriosis can be a long and challenging journey. It can take an average of over six years (sometimes longer) to receive a definitive diagnosis, which can be frustrating and discouraging. Unfortunately, much of this delay in endometriosis diagnosis stems from the misconception that period pain is a normal experience for women. 

This normalization of pain can lead to a lack of urgency in seeking medical attention. If you do not feel that your provider is taking your symptoms seriously, you may want to request an appointment with another provider. While some amount of discomfort around your period may be normal, endometriosis-related pain should not be dismissed, as there are treatments that can help.

The need for surgery to accurately diagnose endometriosis can also be a significant barrier to receiving timely care. Unfortunately, endometriosis cannot be definitively diagnosed by ultrasound, x-ray, or other non-invasive methods.

Surgery

Currently, the standard procedure for diagnosing endometriosis is a minimally invasive surgical procedure called laparoscopy.

During laparoscopy, a surgeon inserts a thin tube with a camera through a small incision in the belly button. Additional small incisions are made for tools to remove endometriosis. Surgeons can remove or destroy endometriosis tissue they find during the surgery.  

To confirm endometriosis, the surgeon will biopsy abnormal tissue and send samples to a lab for analysis. 

Imaging

Deeply infiltrating endometriosis and endometriomas can be seen by imaging techniques, such as ultrasound (done during a pelvic exam) and magnetic resonance imaging (MRI). 

As this technology advances, endometriosis surgeons and radiologists with additional training are getting better at finding these types of endometriosis on imaging. However, it’s still very dependent on the skill of the operator. It’s important to note that imaging can’t rule out endometriosis, and it’s best used to prepare for surgery.

Biomarker tests

While research looking for an endometriosis biomarker test has been ongoing since the late 1980, a reliable test hasn’t been developed. 

Biomarkers are found in tissue, blood, urine, or saliva. Still, many potential markers found in patients with endometriosis overlap with many other conditions, so it’s difficult to determine which markers indicate endometriosis. 

However, a saliva test being studied has the potential to make progress because it’s looking at an overall “signature” (like a collection of biomarkers that come together to spell endometriosis) rather than just specific biomarkers (think of biomarkers as the individual letters.)

Endometriosis treatment

Unfortunately, there’s no cure for endometriosis. Still, there’s the option to treat endometriosis with surgery or options for symptom management by self-management techniques or medication.

It’s important to note that treatment and symptom management are two different things: treatment requires the surgical removal of endometriosis. At the same time, self-management and medication can help the symptoms but not remove the disease. 

It’s important to remember that a hysterectomy doesn’t treat or cure endometriosis; endometriosis lesions don’t go away just because the uterus is removed. A hysterectomy is a treatment option for gynecological diseases such as adenomyosis, which can also be a source of pelvic and period pain.

Surgery

When considering surgery for endometriosis, it's crucial to find a surgeon with specialized training in minimally invasive gynecologic surgery and expertise in treating endometriosis. These surgeons use different methods (like  excision) to remove or destroy endometriosis tissue, adhesions, and scar tissue.

Types of endometriosis surgery

  • Excision: Removing the disease from its root. It goes beyond simply removing what is seen as a “lesion.” This can include removing abnormal appearing tissue. It can be done by laser, “cold” scissors/scalpels, or electrosurgery. Not all techniques are the same, with some causing more surrounding tissue damage than others, but they have the same ultimate goal of cutting out the disease.
  • Ablation or cauterization: Ablation is generally known as burning the surface of endometriosis lesions. However, ablation can also include fulguration, desiccation, or vaporization. This type of treatment aims to remove the surface of the disease. Not all these techniques produce the same effect, as some use more heat or electricity, causing more tissue damage.

Surgery outcomes vary depending on whether the tissue is removed or destroyed with ablation/cauterization. Recurrence is the most commonly discussed outcome, meaning when the endometriosis returns.

Most people that have surgery have less pain for several months after surgery. However, surgery is not a permanent cure, and there is a good chance that the endometriosis tissue will eventually grow back. After surgery, endometriosis is said to have high recurrence rates. However, this data is inconclusive and depends on variables like those who had superficially burnt endometriosis or potentially missed disease. Recurrence rates also depend on the location and type of endometriosis, research methodology, and the length of time since the prior surgery.

When completely removed, the disease can have lower recurrence rates, as low as 10-30%, depending on the location and type of endometriosis, and the length of time since the previous surgery. It's important to note that disease recurrence shouldn't be equated with symptom recurrence when reading publications. Symptom recurrence is much more frequent, whether or not endometriosis is found at subsequent surgery.

There are no standardized requirements or formal organization for this type of surgery, which means the patient must spend time finding the right surgeon for their case. For example, some are uniquely talented at treating bowel endometriosis, while others are uniquely skilled at operating around the pelvic nerves.

Despite being called minimally invasive, endometriosis surgery is still surgery, and it's essential to remember that recovery can take time, especially when the disease has infiltrated surrounding tissues and organs.

Medication 

When dealing with endometriosis, doctors may use medical management alongside surgery, or as a way to manage symptoms if surgery is not possible or desired by the patient.

Initially, doctors may suggest using nonsteroidal anti-inflammatory drugs like Naproxen or Ibuprofen to relieve pain. Hormonal therapy like hormonal birth control may also be offered to manage the symptoms. If birth control doesn't work, a stronger hormone suppression treatment may be recommended. 

The main goal of hormone suppression is to reduce estrogen levels, but it doesn't always relieve the symptoms. Keep in mind that not all lesions will respond to hormone therapy. It's important to remember that there's no clear consensus on what treatment works best, so it may take some trial and error to find what works best for each individual.

Common hormone medications for endometriosis 

  • Combined Oral Contraceptives (COCs): These are birth control pills that contain the hormone estrogen and progestin. It’s not uncommon for a doctor to suggest trying multiple types if one doesn’t work. They each have unique combinations and doses of hormones, so they are not a one-size-fits-all pill.
  • Progestin-only pills: These pills may offer a safer alternative for people with a heightened risk of blood clots or those unable to tolerate pills containing estrogen. It's important to note that these pills don’t contain the same type of progesterone made in the body, so they are instead called progestin.
  • Birth Control Implants/Devices and Injection: These are all progestin-only medications. The implants and devices are called Long-Acting Reversible Contraception (LARC). These include the IUD and the implant, which slowly release progestin over time. The injection is what’s known as the depo-provera shot, which also releases progestin slowly over time.
  • GnRH Medications: GnRH (gonadotropin releasing hormone) medications come in two types: GnRH agonists and GnRH antagonists. These medications can completely shut down ovarian function, leading to medical menopause, as opposed to slightly suppressing the ovaries like other hormone therapies. To reduce side effects, these medications can be combined with estrogen and/or progestin, called add-back therapy. It is uncertain whether they are more effective at relieving symptoms than other hormone suppression methods, and there is insufficient long-term safety data. However, if other treatments fail, some patients may choose to try these medications despite their side effects concerns.
    • GnRH agonists (Lupron or Zoladex) are injections lasting 1 or 3 months that reduce estrogen levels, though it may take a few weeks to see results. However, they are not FDA-approved for use beyond six months due to concerns about bone density loss and potential long-term effects. Clinical trials have shown significant bone loss, with limited recovery even after treatment ends. To mitigate this, they can be FDA-approved for an additional six months if estrogen and/or progestin are added to minimize bone loss and menopausal symptoms. Off-label use for more than one year is possible.
    • GnRH antagonists (Orilissa or Elagolix) are oral medications that rapidly decrease estrogen levels, unlike agonist injections. They are considered safer because they can be stopped immediately, with estrogen levels rebounding shortly after. However, they share similar side effects with GnRH agonists, so add-back therapy is often used. A new oral antagonist, MyFembree, combines medications with estrogen and progestin, known as combination therapy.

FAQ

What is the main cause of endometriosis?

The short answer is that no one knows why some people develop endometriosis. Experts believe that it could be a combination of genetic and immune system factors, but none of these theories fully explain the condition, and it's likely to be due to a combination of factors.

What are 4 symptoms of endometriosis?

Symptoms of endometriosis can vary from person to person, but the most common ones include pelvic pain, painful periods (dysmenorrhea), painful intercourse (dyspareunia), gastrointestinal symptoms like diarrhea, constipation, bloating, or nausea, and difficulty getting pregnant or conceiving.

Does endometriosis go away?

Endometriosis does not have a cure, but treatment options include surgical removal or symptom management through self-care techniques or medication. It's crucial to understand the distinction between treatment, which involves surgical removal, and symptom management, which alleviates symptoms but doesn't eliminate the disease.

Originally published on Mar 22, 2024
Last updated on May 07, 2024