Endometriosis

 Endometriosis occurs when tissue similar to the tissue lining a woman's uterus grows outside the uterus. This tissue behaves like normal uterine tissue during your period, i.e. it breaks down and bleeds at the end of the cycle. But this blood has no outlet - surrounding areas may become inflamed or swollen. This means you may have scars and lesions. Endometriosis most commonly occurs on the ovaries. What are its symptoms? How to deal with endometriosis? What is the characteristic symptom of endometriosis? Why is its effective detection important? We write about it below!

Types of endometriosis

There are three main types of endometriosis, depending on where it occurs:

• superficial peritoneal injury - this is the most common type and causes changes to the peritoneum,
• endometrioma (ovarian change) - dark, fluid-filled cysts, also called chocolate cysts, form deep in the ovaries, do not respond well to treatment, and  can damage healthy tissue,
• deeply infiltrating endometriosis - this type grows under the peritoneum and may involve organs near the uterus, such as the intestines or bladder. About 1% to 5% of women with endometriosis have it

What are the causes of endometriosis?

Doctors cannot pinpoint exactly what causes endometriosis. Some experts believe that menstrual blood containing endometrial cells may pass back through the fallopian tubes into the pelvic cavity, where the cells stick to the organs. This is called retrograde menstruation. 

Your genes may also play a role in this condition. If your mother or sister has endometriosis, there's a good chance you'll get it too. Some women with endometriosis also have immune system disorders, although doctors have not concluded with 100% certainty that there is a link between endometriosis and a disorder of the immune system. 

 

Endometriosis and complications

The severe pain associated with endometriosis can affect your quality of life. Some women struggle with anxiety or depression. Medical treatments and psychiatric care can help. Endometriosis can increase the risk of ovarian cancer or another cancer called endometriosis-associated adenocarcinoma.

 

Endometriosis and fertility

Endometriosis is the leading cause of infertility. It affects approximately 5 million women in the United States. Endometriosis affects your reproductive organs and therefore your ability to get pregnant may become an issue because:

• endometrial tissue wraps around the ovaries, which can block the release of eggs, 

• tissue can block sperm from reaching the fallopian tubes,

• endometriosis can stop a fertilized egg from sliding down the fallopian tubes into the uterus.

• alter your body's hormonal chemistry,

• cause your body's immune system to attack the embryo

• affect the layer of tissue lining the uterus where the egg is implanted.

Your doctor may surgically remove endometrial tissue. This paves the way for the sperm to fertilize the egg. If surgery is not an option, you may consider intrauterine insemination (IUI), which involves inserting your partner's sperm directly into the uterus. There is also the option of combining IUI with 'controlled ovarian hyperstimulation', which means using medication to help your ovaries produce more eggs. Women who use this technique are more likely to become pregnant than those who do not. Another option is in vitro fertilization (IVF). This may increase your chances of conceiving, but IVF pregnancy statistics vary.

 

Pain and other symptoms of endometriosis

You may not notice any symptoms at first, but these include:

• period back pain,

• severe menstrual cramps,

• pain during a bowel movement, especially during menstruation,

• unusual or heavy menstrual bleeding,

• blood in stool or urine,

• diarrhea or constipation,

• painful sex,

• permanent fatigue,

• problems getting pregnant.

Pain and infertility are common symptoms, although 20–25 % of women are asymptomatic. The presence of pain symptoms is related to the type of endometrial lesions, as 50% of women suffer from typical lesions, 10% of women struggle with ovarian cystic lesions and 5% of women struggle with deep endometriosis and do not feel pain.
 

Infertility 

About a third of women with infertility have endometriosis. About 40% of people with endometriosis are infertile. The pathogenesis of infertility depends on the stage of the disease: in the early stages of the disease, it is assumed to be secondary to an inflammatory reaction that impairs various aspects of conception, while in the later stages of the disease, distorted pelvic anatomy and adhesions contribute to impaired conception

 

Other symptoms

Other symptoms include diarrhea or constipation, chronic fatigue, nausea and vomiting, migraines, fever, heavy or irregular periods, and hypoglycemia. There is an association between endometriosis and some types of cancer, especially some types of ovarian cancer, non-Hodgkin's lymphoma, and brain cancer. Endometriosis is not related to endometrial cancer. Rarely, endometriosis can cause endometrial-like tissue to be found in other parts of the body. Chest endometriosis produces the following symptoms: coughing up blood, a collapsed lung, or bleeding into the pleural cavity. In addition, stress can be a cause or consequence of endometriosis. 

 

Physical health

Complications of endometriosis include internal scarring, adhesions, pelvic cysts, ovarian chocolate cysts, ruptured cysts, and intestinal and ureteral obstruction resulting from pelvic adhesions. Endometriosis-related infertility can be equated with scar formation and anatomical deformities caused by endometriosis. Ovarian endometriosis can complicate pregnancy with an abscess or rupture.

Thoracic endometriosis, in turn, may be associated with menstrual recurrent thoracic endometriosis syndrome, which includes pneumothorax in the arms in 73% of women and pulmonary nodules in 6% of cases. 
 

Mental health
 

Endometriosis is associated with an increased risk of developing depression and anxiety disorders . Research suggests this is partly due to the pelvic pain experienced by endometriosis patients. Pelvic pain has been shown to have a significant negative impact on women's mental health and quality of life, with women suffering from pelvic pain in particular reporting high levels of anxiety and depression, loss of ability to work, limited social activities and poor quality of life. 

Genetics
 

Endometriosis is an inherited disease affected by both factors both genetic and environmental. Children or siblings of people with endometriosis are more likely to develop endometriosis; low levels of progesterone can be genetic and may contribute to hormonal imbalance. There is an approximately six-fold increase in the incidence of the condition  in those with an affected first-degree relative.

Environmental toxins
 

Some factors associated with endometriosis include prolonged exposure to estrogen such as during menopause or obstruction of the menstrual outflow, e.g. in Müllerian anomalies. Several studies have explored the potential link between dioxin exposure and endometriosis, but the evidence is inconclusive and the potential mechanisms are poorly understood. A 2004 review of dioxin and endometriosis studies found that the human data supporting a dioxin-endometriosis link are sparse and conflicting. In contrast, a 2009 review indicates that there is insufficient evidence to support a link between exposure to dioxins and the development of endometriosis. 

 

Structure of the endometrium

Main theories for the formation of ectopic endometrial-like tissue include retrograde menstruation, müllerianosis, coelomic metaplasia, stem cell dissemination in blood vessels and surgical transplantation. Each of them is described in more detail below.

 

Theory of retrograde menstruation

The retrograde menstrual theory (also called the implantation theory or the transplantation theory) is the most widely accepted theory regarding the spread and transformation of the ectopic endometrium into endometriosis. This suggests that during a woman's menstruation, some endometrial debris flows back through the fallopian tubes into the peritoneal cavity, attaching itself to the surface of the peritoneum (the lining of the abdomen), where it can further invade tissue or develop into endometriosis. 

 

Location

Endometriosis is most common on:

• ovaries,
• fallopian tubes,
• the tissue that holds the uterus in place (ligaments),
• the outer surface of the uterus,

Less popular places are:

• vagina,
• cervix,
• vulva,
• gut,
• bladder,
• rectum.

 
Endometriosis can spread to the cervix and vagina, or to the sites of surgical abdominal incision, known as "cicatricial endometriosis". Recto-vaginal or intestinal endometriosis affects about 5-12% of people with endometriosis and can cause severe pain during bowel movements.

Deeply infiltrating endometriosis is defined as the presence of endometrial glands and stroma infiltrating the subperitoneal tissue above 5 mm. The prevalence of DIE is estimated at 1 to 2%. Deep endometriosis usually presents as a solitary nodule in the vesico-uterine fold or in the lower 20 cm of the intestine. Deep endometriosis is often associated with severe pain.
 
 

Extra-pelvic endometriosis

Rarely, endometriosis occurs in parts of the body outside the pelvis, such as the lungs, brain and skin. “Scarring endometriosis” may occur in surgical abdominal incisions. Risk factors for scarring endometriosis include previous abdominal surgery such as hysterotomy or caesarean section, ectopic pregnancy, postpartum salpingotomy, laparoscopy, amniocentesis, appendectomy, episiotomy, vaginal hysterectomy, and hernia repair. Endometriosis can also manifest as skin lesions in cutaneous endometriosis.

Less commonly, lesions can be found on the diaphragm or lungs. Diaphragmatic endometriosis is rare, almost always in the right hemidiaphragm, and can cause cyclical pain in the right scapula (shoulder) or cervical region (neck) during the menstrual period.

 

Diagnosis

Your health history and physical examination may lead your doctor to suspect endometriosis. There is a clear benefit to undergoing a diagnostic ultrasound (TVUS) procedure as the first step in screening for endometriosis. There are significant delays in diagnosis for many patients. Research shows that in the United States the average delay is 11.7 years. Patients in the UK have an average delay of 8 years and in Norway 6.7 years. A third of women consulted their GP six or more times before being diagnosed. 

The most common sites of endometriosis are the ovaries, followed by the capsule of Douglas, the posterior leaves of the broad ligaments, and the sacro-uterine ligaments. For deep infiltrating endometriosis, TVUS, TRUS and MRI are non-invasive diagnostic techniques with high sensitivity and specificity.

 

Laparoscopy

Laparoscopy, a surgical procedure where a camera looks into the abdominal cavity, is the only way to accurately diagnose the extent and severity of endometriosis pelvic/abdominal. Laparoscopy is not suitable for examining sites outside the pelvis, such as the navel, hernial sacs, abdominal walls, lungs or kidneys. 

Studies conducted in 2019 and 2020 showed that with the advances in imaging, the diagnosis of endometriosis should no longer be considered synonymous with immediate laparoscopic diagnosis, and also showed that endometriosis should be classified as a syndrome that requires confirmation of visible changes during laparoscopy in addition to the characteristic symptoms .

Laparoscopy allows visualization of the lesion, unless the lesion is externally visible (e.g. endometrial nodule in the vagina) or is located outside the abdominal cavity. If growths (lesions) are not visible, a biopsy should be performed to establish the diagnosis. Diagnostic surgery also allows for simultaneous surgical treatment of endometriosis.

 

USG 

Vaginal ultrasound has clinical value in the diagnosis of endometriosis and before surgery in the case of deep endometriosis. This concerns the identification of the spread of the disease in people with a well-established clinical suspicion of endometriosis. Vaginal ultrasound is inexpensive, readily available, has no contraindications, and requires no preparation. Health professionals performing ultrasound examinations must be experienced. By extending the ultrasound assessment to the posterior and anterior pelvic compartments, the ultrasound scanner is able to assess structural mobility and look for deeply infiltrating endometrial nodules, paying attention to size, location and distance from the anus.

 

Magnetic Resonance

The use of MRI is another method of detecting changes in a non-invasive way. MRI is not widely used due to its cost and limited availability, but it has the ability to detect the most common form of endometriosis (endometrioma) with sufficient accuracy. 

 

Sequences

T1W testing with or without fat suppression is recommended for endometrial tumours; while sagittal, axial and oblique 2D T2W are recommended for deep infiltrating endometriosis.

 

Stage

Surgically, endometriosis can be classified into categories I–IV of the 1997 revised classification of the American Society of Reproductive Medicine. The process is a complex system scoring, which assesses changes and adhesions in the pelvic organs, but it is important that only physical disease is assessed, not the level of pain or infertility. A person with stage I endometriosis may have little disease and severe pain, while a person with stage IV endometriosis may have severe disease and no pain, or vice versa. In principle, the different stages of the disease are presented below:
 

• Stage I (minimal) - the results are limited to only superficial changes and possibly a few transparent adhesions,
• Stage II (mild) - changes occur,
• Stage III (moderate) - there are more endometrial nodules on the ovary and more adhesions,
• Stage IV (hard) - large endometrial nodules, extensive adhesions. Implants and adhesions may be outside the uterus. Large ovarian cysts are common.

Endometriosis markers

The area of research is the search for endometriosis markers. In 2010, essentially all proposed endometriosis biomarkers had unclear medical applications, although some appear promising. The only biomarker used in the last 20 years is CA-125. A 2016 study found that this biomarker was present in people with symptoms of endometriosis; and once ovarian cancer has been ruled out, a positive CA-125 result can confirm the diagnosis. Its effectiveness in excluding endometriosis is low. CA-125 levels appear to decrease during endometriosis treatment, but no correlation with the disease has been shown. 

Another 2011 review identified several putative biomarkers after biopsy, including findings of small sensory nerve fibers or a defectively expressed β3 integrin subunit. It has been suggested that a future diagnostic tool for endometriosis will consist of a panel of several specific and sensitive biomarkers, covering both substance concentrations and genetic predisposition.

A 2016 study of endometrial biomarkers for diagnosing endometriosis was unable to be conducted effectively due to low-quality evidence. It should be noted that microRNAs have the potential to be used in diagnostic and therapeutic decisions.

 

VAS and NRS pain rating

The most common pain scale for quantifying endometriosis pain is the visual analog scale (VAS).  VAS and numerical rating scale (NRS) were the best suited scales to measure pain in endometriosis. For research purposes and more detailed measurement of pain in clinical practice, a VAS or NRS for each type of typical endometriosis pain (dysmenorrhea, deep dyspareunia, and nonmenstrual chronic pelvic pain), combined with a global clinical impression (CGI) and a quality scale is used life.

 

Prevent

Some evidence shows COC use is associated with a reduced risk of endometriosis, as is regular exercise and avoiding alcohol and caffeine. 

 

Endometriosis treatment

Although there is no cure for endometriosis, there are two ways to treat it; treatment of pain and treatment of infertility associated with endometriosis. In many cases, menopause (natural or surgical) will weaken this process. At reproductive age, endometriosis is only treated - the goal is to relieve pain, limit progression of the process, and restore or preserve fertility if needed. In younger people, some surgical procedures aim to remove the endometrial tissue and preserve the ovaries without damaging the healthy tissue. Drug treatment for pain may be initiated based on the presence of symptoms, and on examination and ultrasound findings that have ruled out other potential causes.

In general, the diagnosis of endometriosis is confirmed during surgery where ablative steps can be taken. What happens next depends on the circumstances - a person without fertility problems can manage symptoms with painkillers and hormone medications that inhibit the natural cycle, while an infertile person can be treated expectantly with surgery, infertility drugs or IVF.

A 2020 Cochrane systematic review found that for all types of endometriosis, it is uncertain whether laparoscopic surgery improves overall pain compared to diagnostic laparoscopy. 

 

Surgery 

Surgery, if performed, should generally be done laparoscopically, not openly. Treatment consists of ablation or excision of endometriosis, electrocoagulation, lysis of adhesions, resection of endometrial tumors and restoring, if possible, normal pelvic anatomy. When laparoscopic surgery is used, small instruments are inserted through the incisions to remove endometriosis tissue and adhesions. Because the incisions are very small, only minor scars will be left on the skin after the procedure, and most people recover quickly from surgery and have a reduced risk of adhesions. Many endometriosis specialists believe that excision is the ideal surgical method for treating endometriosis.

When it comes to deep endometriosis, segmental resection or nodule removal is effective but is associated with a significant complication rate of approximately 4.6%. Historically, a hysterectomy (removal of the uterus) was thought to be the cure for endometriosis in those who did not wish to become pregnant. Removal of the uterus may be beneficial as part of treatment if the uterus itself is affected by adenomyosis. However, this should only be done in conjunction with endometriosis removal by excision. If endometriosis is not removed during a hysterectomy, pain may persist.

A presacral neurectomy can be performed where the uterine nerves are cut. However, this technique is not usually used due to the high incidence of associated complications, including presacral hematoma, and irreversible problems with urination and constipation.

 

Does endometriosis recur? 

The underlying process that causes endometriosis may persist after surgical or medical intervention. A study has shown that dysmenorrhea recurs at a rate of 30% within a year after laparoscopic surgery. The revival of lesions tends to appear in the same location if they have not been completely removed during surgery. Laser ablation was shown to result in higher and earlier recurrence rates compared to endometrial cystectomy, and recurrence after repeat laparoscopy was similar to that after the first operation. Endometriosis can recur after hysterectomy and bilateral salpingo-oophorectomy. The probability of return in this case is about 10% chance. Recurrence of endometriosis after conservative treatment is estimated at 21.5% after 2 years and 40-50% after 5 years after surgery.

 

Complication risk and safety of pelvic surgery

The risk of complications after surgery depends on the type of lesion that has been operated on. Between 55% and 100% of people will have adhesions after pelvic surgery, which can result in infertility, chronic abdominal and pelvic pain, and difficult surgical procedures. Trehan's temporary ovarian suspension - a technique that suspends the ovaries for a week after surgery, can be used to reduce the incidence of adhesions after endometriosis surgery. Removal of an ovarian cyst without removal of the ovary is a safe procedure.

 

Endometriosis and infertility treatment

Surgery is more effective than medical intervention in treating endometriosis-related infertility. Surgery aims to remove endometrial-like tissue and preserve the ovaries without damaging healthy tissue. Taking hormone suppressive therapy after surgery can be positive for endometriosis recurrence and pregnancy. In vitro fertilization (IVF) procedures are effective in improving fertility in many people with endometriosis.

When treating infertility, ultra-long GnRH agonist pre-treatment results in a higher chance of pregnancy in people with endometriosis compared to short pre-treatment.

 

Research

Preliminary studies in mouse models have shown that monoclonal antibodies as well as inhibitors of the MyD88 signaling pathway can reduce lesion volume. Thanks to this, clinical trials are conducted on the use of a monoclonal antibody directed against IL-33 and anakinra - an antagonist of the IL-1 receptor. Promising preclinical results lead clinical trials to test cannabinoid extracts, dichloroacetic acid and turmeric capsules.

 

Epidemiology in society

Determining how many people have endometriosis is difficult because final diagnosis requires surgical visualization using laparoscopic surgery. Criteria commonly used to establish a diagnosis include pelvic pain, infertility, surgical evaluation, and in some cases MRI. Ultrasound can identify large clumps of tissue as potential endometriosis lesions and ovarian cysts, but it is not effective in all patients, especially with smaller, superficial lesions. 

These studies suggest that endometriosis affects approximately 11% of women in the general population. Endometriosis is most common in people in their thirties and forties; however, it can start as early as age 8.


How to prevent endometriosis?

Warm baths, hot water bottles, and heating pads can quickly relieve endometriosis pain. Over time, the following lifestyle changes may also help:

Healthy Diet -Studies have found a link between endometriosis and diets low in fruits and vegetables and high in red meat. Some experts believe that the high amount of fat in meat like beef encourages the body to produce chemicals called prostaglandins, which can lead to more estrogen production. This extra estrogen can cause excess endometrial tissue to grow. Add more fresh fruits and vegetables, making them the main ingredient in your meals. Storing washed and cut fruit and vegetables in the fridge can help you eat more of them.
Studies have also shown that foods rich in omega-3 fatty acids, such as salmon and walnuts, are helpful. One study found that women who consumed the highest amount of omega-3 fatty acids were 22% less likely to develop endometriosis than women who consumed the least. By comparison, women who ate the most trans fat had a 48% higher risk than those who ate the least, so the type of fat they eat matters.

Also avoid alcohol and caffeine - Drinking caffeinated coffee and soda seems to increase the chances of developing endometriosis, although scientists are uncertain about this due to the small amount of research. 

Exercise regularly - There are many reasons why exercise is a great way to manage endometriosis. Exercise encourages the heart to pump blood to all organs, improve circulation, and support the flow of nutrients and oxygen to all systems of the body. Women who also exercise may have less estrogen and weaker periods, which over time can help ease endometriosis symptoms. Studies have shown that the more time you spend in high-intensity exercise, such as running or cycling, the less likely you are to develop endometriosis.
Exercise helps reduce stress, and because it releases chemicals called endorphins in the brain, it can actually relieve pain. Even a few minutes of physical activity that makes you gasp or sweat can trigger this effect. Lower-intensity workouts like yoga can also be beneficial as they stretch the pelvic tissues and muscles to relieve pain and reduce stress.

Cope with stress - researchers believe that stress can make endometriosis worse. In fact, the condition itself can cause stress due to severe pain and other side effects. Finding ways to deal with stress – whether through yoga, meditation or simply making time for self-care – may help to alleviate the symptoms of the disease. Seeing a therapist who can give you tips on managing stress can also help.

Look at alternative therapies - while there is not enough research to support the use of alternative natural endometriosis therapies, some women find relief from their symptoms with these techniques and the solutions below:

• acupuncture,

• herbal medicine,

• ayurveda,

• massage.

If you want to try an alternative therapy, talk to your doctor first, especially if you are considering taking over-the-counter supplements. These types of therapies can cause side effects that you are not aware of. Never exceed the recommended dose of a drug and supplement, or take more than one supplement at a time.

The causes of endometriosis are not fully known. However, the diagnosis of endometriosis is extremely important. Thanks to this, pharmacological treatment, non-steroidal anti-inflammatory drugs or surgical treatment of endometriosis can help not only to get rid of pain, but also fertility problems. It is important to determine the focus of endometriosis, as it can be significant in the course of endometriosis and in determining the best method of treatment. Let's remember that this is a disease that affects women of all ages, which makes prevention so important!