What is Endometriosis?

– Written by Managing Director of Pillar Healthcare, Mark Whitney, for a leading fertility clinic in the UK.

Endometriosis (pronounced en-doe-me-tree-o-sis) is an often painful disorder in which tissue that normally lines the inside of your uterus — the endometrium — grows outside your uterus. Endometriosis most commonly involves the ovaries, bowel or the tissue lining your pelvis. In rare instances, endometrial tissue may spread beyond the pelvic region.

Endometriosis is a common condition that affects women during the reproductive years. The condition is estimated to affect around two million women in the UK. Most of them are diagnosed between the ages of 25 and 40.

Up to 10% of all women may have endometriosis. Many women who have endometriosis experience few or no symptoms. Some women experience severe menstrual cramps, chronic pelvic pain, or painful intercourse. In others, infertility may be the only symptom of endometriosis.

Some specialists feel that endometriosis is more likely to be found in women who have never been pregnant, most likely the development of endometriosis and potential fecundity issues developing simultaneously. Endometriosis may be found in 24% to 50% of women who experience infertility and in more than 20% who have chronic pelvic pain. Endometriosis is classified into one of four stages (I-minimal, II-mild, III-moderate, and IV-severe) depending on location, extent, and depth of endometriosis implants; presence and severity of adhesions; and presence and size of ovarian endometriomas.

How can/does Endometriosis develop?

Medical experts do not know why some women develop endometriosis, or are unwilling to provide a definitive reason why it develops. During each menstrual period, most of the uterine lining and blood is shed through the cervix and into the vagina. However, some of this tissue enters the pelvis through the fallopian tubes. Women who develop endometriosis simply may be unable to clear the pelvis of these cells. As of the time of this writing, there is no single unifying theory as to the genesis of endometriosis; although several have been proposed. However, most reviews of the literatures show that endometriosis is oestrogen-dependent and often progressive, resulting in worsening pain and other symptoms over time.

There are several different ideas of how and why endometriosis happens. One idea is that when a woman has her period, some of the blood and tissue from her uterus travels out through the fallopian tubes and into the abdominal cavity. This is called retrograde menstruation. Another idea is that some cells (stem cells) in the body outside of the uterus can change to become the same kind of cells that line the uterus. This is a common explanation for endometriosis at unusual sites like the thumb or knee and the nose. Another possible explanation is that the cells from the lining of the uterus travel through the blood vessels or through the lymphatic system to reach other organs or body areas. Also, endometriosis can spread at the time of surgery. Interestingly, nearly all women have some degree of retrograde menstruation, but only a few women will get endometriosis. This may be due to differences in a woman’s immune system and hormonal profile.

Hormonal Imbalance

Hormonal imbalance may contribute to endometriosis as well. During a woman’s menstrual cycle, endometrial tissue grows and then regresses. Oestrogen is responsible for the proliferation of the endometrial lining. The growth and progression of endometriosis is also dependent on oestrogen and can be treated by suppressing oestrogen levels. From Pillar Healthcare’s prospective, natural progesterone supplementation will fare better than synthetic hormones. As oestrogen is responsible for the endometriums development, an oestrogen imbalance or more accurately, a hormonal imbalance can aid the development of endometriosis and/or worsen its symptoms.

Signs & Symptoms

Most women have minimal or mild endometriosis, which is characterized by superficial implants and mild adhesions. Moderate and severe endometriosis is characterized by chocolate cysts and more severe adhesions. The stage of endometriosis does not correlate with the presence of, or severity of symptoms; with stage IV endometriosis, infertility is very likely.

Inflammation may also play an important role in endometriosis. Endometriotic tissue produces excess inflammatory mediators such as prostaglandin E2 and prostaglandin F2α. In addition to helping ectopic endometrial tissue implants grow in other parts of the body, inflammation may also play an important role in the pain caused by endometriosis. Endometrial tissue in areas outside the uterus can trigger an immune response that causes the release of large amounts of inflammatory cytokines. These cytokines may increase the activity of immune cells, such as mast cells, which can affect nearby nerves and contribute to pain. In addition to increased overall inflammation, women with endometriosis may have defects in their immune systems that make it easier for endometrial tissue to grow and survive.

Endometriosis is a long-term (chronic) condition. Symptoms can vary significantly from person to person, and some women have no symptoms at all. The most common symptoms include:

• painful periods or heavy periods
• pain in the lower abdomen (tummy), pelvis or lower back
• pain during and after sex
• bleeding between periods
• difficulty getting pregnant

Most women with endometriosis get pain in the area between their hips and the tops of their legs. Some women experience this pain all the time. Other symptoms may include:

• persistent exhaustion and tiredness
• discomfort when going to the toilet
• bleeding from your (rectum) or blood in your faeces
• coughing blood – in rare cases when the endometriosis tissue is in the lung

Risk Factors

Several factors place you at greater risk of developing endometriosis, such as:

• Never giving birth
• One or more relatives (mother, aunt or sister) with endometriosis
• Any medical condition that prevents the normal passage of menstrual flow out of the body
• History of pelvic infection
• Uterine abnormalities

Endometriosis usually develops several years after the onset of menstruation (menarche). Signs and symptoms of endometriosis end temporarily with pregnancy and end permanently with menopause, unless you’re taking oestrogen. Exposure to certain pesticides (eg, organochlorine) may also increase the risk of endometriosis. Diet may also play a role, as some research has suggested that a diet low in vegetables and omega-3 fatty acids and high in red meat and trans fats may increase the risk of endometriosis.

Certain chemicals are associated with an increased prevalence of endometriosis. These include polychlorinated biphenyls (PCBs), which were once commonly used in electrical equipment, hydraulic fluid, and carbonless carbon paper; phthalates, used as plasticizers to increase plastic flexibility and durability; and organochlorine pesticides (OCPs), which were widely popular in agriculture practices. These chemicals can act in a variety of ways. Organochlorines bind to estrogen receptors and mimic hormones that in turn can affect endocrine pathways and alter hormonal function. A study conducted in 2005 showed that women exposed to PCBs have a higher prevalence of endometriosis. Researchers did examine urinary phthalate metabolite concentrations in relation to endometriosis, using data from the National Health and Nutrition Examination Survey (NHANES) from 1999-2004, and found that exposure to monobutyl phthalate (MBP) is positively correlated with endometriosis risk. In an analysis conducted using data from the Women’s Risk of Endometriosis (WREN) study, increased endometriosis risk was associated with higher serum concentrations of organochlorines, including β-hexachlorocyclohexane (HCH) and mirex.

Diagnosing Endometriosis

To diagnose endometriosis, a doctor must perform a laparoscopy (a surgery where a doctor looks in the abdomen with a camera usually through the belly button) and take a sample of a suspected endometriosis lesion. Some physicians and patients may try to treat suspected endometriosis with certain medications to see if symptoms are improved without having to undergo surgery. Although this may be possible, endometriosis cannot be diagnosed by improvement in symptoms with medication alone. During surgery, endometriosis lesions are often described as looking like “cigarette burns” inside the abdomen, although there are many different variations as to how an endometriosis lesion may appear.

Conventional Treatment of Endometriosis

There are many treatment options for endometriosis; however, there is no consensus that one type of therapy is superior to another.

The most conservative therapy for endometriosis is with medications. Non-steroidal, anti-inflammatory medications, like ibuprofen, may help with the pain associated with endometriosis. Some doctors may prescribe medications that affect a woman’s hormones in order to help with endometriosis pain. Some examples are oral contraceptive pills and gonadotropin releasing hormone (GnRH) agonists, the latter of which put women into a “temporary” menopause-like state.

Surgery can not only help to diagnose endometriosis, but can also be used to treat endometriosis. Surgery can be used to remove the endometriosis or to burn the endometriosis lesions outside of the uterus to make them go away. It is also used to get rid of scar tissue so that the ovaries and tubes can go back to their normal location in the pelvis. Danocrine (Danazol®) is another effective treatment option. It is a synthetic hormone that works by creating a lower oestrogen, higher androgen environment resulting in a reduction of endometriosis lesions. Although effective, it can cause weight gain, depression, reduced breast size, deepening of the voice, skin rash, and increased body hair.

A fundamental problem with conventional medicine’s approach to many women’s health concerns is the reliance upon synthetic hormones. Copious evidence shows that natural bioidentical hormones may offer a safer alternative. However, most conventional treatment is carried out through synthetic hormones. Since unopposed or excessive oestrogenic activity drives endometriosis, many women with this condition are treated with synthetic oestrogens and synthetic progestins, which mimic the action of oestrogen and progesterone but are structurally different than the oestrogen and progesterone produced naturally in a woman’s body. This exposes them unnecessarily to increased risk of several diseases, including breast cancer and heart disease.

Pharmacological management of endometriosis must be set within the framework of long-term therapeutic strategies. As the available drugs are not curative, treatments will need to be administered for years or until women desire a pregnancy.

How does endometriosis impair fertility?

In advanced endometriosis, large endometriomas and extensive pelvic adhesions can disrupt the normal anatomic relationship between the fallopian tubes and the ovaries, creating an obvious impediment to conception. However, in minimal or mild disease it is unclear how a few superficial lesions can reduce the monthly fecundity rate from a normal of about 20% down to 2% to 3%. A possible mechanism of infertility is that endometriosis generates a local peritoneal inflammatory response, leading to immune dysfunction and altered levels of prostaglandins, growth factors, and cytokines. Increased numbers of peritoneal macrophages may phagocytose sperm and reduce their fertility potential. There is enough evidence to suggest that if a woman has developed endometriosis, there is most likely a hormonal insufficiency. This in itself can impair fertility.

Natural Treatment of Endometriosis

The pain and infertility associated with endometriosis are likely due to increased levels of inflammation. Omega-3 fatty acids have generated interest because of their anti-inflammatory abilities. These anti-inflammatory capabilities are likely one mechanism by which omega-3 fatty acids help prevent the development of endometriosis.

Many lines of evidence suggest that oxidative stress, which is caused by reactive oxygen species, contributes to several aspects of endometriosis. Therefore, it is not surprising that vitamins E and C, both of which possess considerable antioxidant properties, have been studied in the context of endometriosis. In a study of 91 infertile women, those with endometriosis were shown to have lower levels of vitamin C in their follicular fluid (fluid surrounding the eggs in the ovaries) compared to women who did not have endometriosis. In general, women with endometriosis also had lower levels of the endogenous antioxidant superoxide dismutase in their plasma.

Other evidence suggests that lower intake of antioxidants, including vitamins E and C, selenium, and zinc, in women with endometriosis correlate with more severe disease.

N-acetyl cysteine (NAC) is a modified form of the natural amino acid cysteine. It exerts several direct anti-oxidative actions and helps bolster the body’s intrinsic ability to combat oxidative stress by aiding the production of the endogenous antioxidant glutathione. Another study that examined the effects of NAC treatment both in human cell culture and in mice found that it reduced the oxidative stress burden and cellular proliferation in endometriosis. These findings led the researchers to conclude “Our model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis”.

Aiming for the reduction of oxidative stress as the treatment goal for endometriosis looks promising. Oxidative stress plays an important role in the pathogenesis and progression of endometriosis. Agents with antioxidant activity are able to improve Chronic Pelvic Pain (CPP) without undesired effects and any important metabolic changes associated with hormonal suppression therapy. A conclusion drawn from a recent study into antioxidants and CPP states that, dietary therapy with antioxidants could be considered as a new effective strategy in the long term for CPP, and may be better accepted by patients.

In another study, women who had a lower intake of antioxidants in comparison to women who consumed more antioxidants were more likely to develop endometriosis. Vitamin D has been shown to improve endometriosis.

The NutriSIG team: Associate Professor Kaylon Bruner-Tran (chair), Dr Gil Wilshire (chair elect), Nutritionist Dian Shepperson-Mills (immediate past chair), and Professor Kevin Osteen (NutriSIG member), were tasked with demonstrating what science there is available to back-up clinical science when it comes to improving fertility through nutritional medicine.

Key messages included that women with endometriosis, who are trying to conceive, should be trying to eat a diet which reduces inflammation in the body, because inflammation affects fertility (and pain, of course!). For you to absorb the nutrients from your food to deal with inflammation you must have a healthy digestive tract.

Women who get more physical activity have a reduced risk of developing endometriosis.

Finally, a literature review analysed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with Nacetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis (Nutritional aspects related to endometriosis – A Review).

After the review in May 2016, Pillar Healthcare have come to a series of conclusions. Overall, the general understanding of Endometriosis and other diseases of the reproductive system tend to follow a standard treatment model. This treatment model is based on drug therapy, mostly hormonal and surgery.

The scientific community have still yet to determine a clear protocol on how endometriosis is developed and how it should be treated. Better education on the subject to young women will have longer lasting benefits than the current model. Sexual education, anatomy and physiology and what can go wrong should be thought/ discussed more efficiently and regularly in society. Decisions that we make on a daily basis are either working for us or against us. If I choose not to exercise today, that’s ok but if I do this more often than not, health problems will arise.

Overall, the scientific community, as mentioned have yet to determine a stance on endometriosis and other diseases of the reproductive system, like Polycystic Ovarian Syndrome and Fibroids. However, it is clear to see that many of these diseases are linked to a clear set of risk factors, that if addressed, can limit the prevalence of this disease.

It is our belief that more should be done to correct hormonal imbalances earlier in the female, before more serious problems can develop. This coupled with a greater understanding of the body and what is classed as normal will allow people, women in this case to be more involved in their treatment.

It is our opinion that:

• Addressing the hormonal imbalance or hormonal insufficiency whilst examining the larger endocrine/ hormonal system as a whole should be the starting point. If there are any insufficiencies in this system, over time this will develop into a larger concern
• Chemicals have provided some wonderful additions to our lives over the past century.  The EU’s Contamed Project stated that many pesticides and fungicides allowed in the EU are harmful to our health and can might be cancerous. This is but one example
• Nutrient deficiencies that persist for years and years. A simple examination of Magnesium shows us that it is involved in over 300 biochemical processes. If one becomes deficient in Magnesium, these 300 processes will not be performed well or at all
• And of course our diets and lifestyle has changed massively in the past 50 years that has increased obesity, but left us under-nourished

By addressing the above we believe that:

• Improving the hormonal system will curb any oestrogenic effects on sensitive tissues
• Removing substances that have proven and/or suspected links to our toxic load or are hormonal mimickers (the negative kind) will remove direct manipulation of our hormones but also reduce any epigenetic impact on sensitive tissues and allow the liver to detoxify used hormones and other substances more efficiently
• By improving our nutrient and phytonutrient intake, we can better support the systems involved in the development of these issues – the reproductive, the immune and the endocrine system
• By improving how we choose to live our lives, whether by increasing our exercise, reducing our stress load or being more aware of our daily choices can have on the pathogenesis of such diseases

This is succinctly demonstrated in a paper by Prof. D.J.P. Barker of the University of Southampton,  the following extract being a summary quotation from that paper:

Coronary heart disease, type 2 diabetes, breast cancer and many other chronic diseases are unnecessary. Their occurrence is not mandated by genes passed down to us through thousands of years of evolution. Chronic diseases are not the inevitable lot of humankind. They are the result of the changing pattern of human development. We could readily prevent them, had we the will to do so. Prevention of chronic disease, and an increase in healthy ageing require improvement in the nutrition of girls and young women. Many babies in the womb in the Western world today are receiving unbalanced and inadequate diets. Many babies in the developing world are malnourished because their mothers are chronically malnourished. Protecting the nutrition and health of girls and young women should be the cornerstone of public health. Not only will this prevent chronic disease, but it will produce new generations who have better health and well-being through their lives.