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Navigating Endometriosis: Latest Insights and Natural Treatment Strategies from Functional Medicine
Endometriosis is a complex and often misunderstood condition that affects millions of women worldwide. It occurs when the tissue similar to the lining of the uterus, known as the endometrium, grows outside the uterus. This misplaced tissue can be found in various areas of the body, such as the ovaries, fallopian tubes, pelvic lining, and even distant organs like the bladder or intestines.
Unlike the normal endometrial tissue that sheds during menstruation, the displaced endometrial tissue has no means of exit from the body. This can lead to the formation of painful adhesions, scar tissue, and the development of cysts, causing a range of symptoms and complications.
Early warning signs
It is often difficult to evaluate endometriosis by physical examination and clinical history review. The warning signs include:
Presentation and Diagnosis
Endometriosis most often occurs on or around reproductive organs in the pelvis or abdomen, including:
- Fallopian tubes
- Ligaments around the uterus (uterosacral ligaments)
- Lining of the pelvic cavity
- Outside surface of the uterus
- Space between the uterus and the rectum or bladder
More rarely, it can also grow on and around the:
- Stomach (abdomen)
- Vagina or vulva
Endometrial tissue growing in these areas does not shed during a menstrual cycle like healthy endometrial tissue inside the uterus does. The buildup of abnormal tissue outside the uterus can lead to inflammation, scarring and painful cysts. It can also lead to adhesions – the buildup of fibrous tissues between reproductive organs that causes them to “stick” together.
Diagnosing endometriosis requires a combination of medical history, physical examination, and imaging tests such as ultrasound or MRI. A definitive diagnosis can only be made through laparoscopy, a surgical procedure in which a thin tube with a camera is inserted through a small incision in the abdomen to view the pelvic organs and remove any abnormal tissue for biopsy.
Some of the procedures to diagnose a suspected case of endometriosis are
Diagnosis delays – it’s something else
A US survey found that 75.2% of endometriosis sufferers were initially misdiagnosed as either having another physical disorder or mental health issue and many doctors choose to go down the route of symptom management like pain relief or hormonal medication without any formal diagnosis.
For those that insist on finding an answer to their debilitating symptoms, pursuing the issue takes time and patience. A US study found that 23.5% of endometriosis patients see 5 or more physicians before receiving a diagnosis. And the more physicians patients saw, the longer the diagnostic delay. Those that only saw 1 to 2 doctors received a diagnosis in 1 to 2 years, while this increased to 7 to 8 years for those that saw 5 to 9 physicians.
Why is there such a delay in the diagnosis of endometriosis? Studies have found that women are less likely to feel listened to and taken seriously, and are assumed to have a higher pain threshold. One of the main side effects of endometriosis is chronic pain, and because endometriosis patients don’t receive a definitive diagnosis until they’ve had laparoscopic surgery, not having their pain believed can be particularly harmful.
Activists have used the term ‘gender health gap’ to bring together evidence that would suggest that your gender has a bearing on your experience with doctors and the healthcare you receive. Studies that point out that women are 25% less likely than men to receive pain relief have been used to back up the notion of gender bias in medicine.
In a study published in 2018, entitled “Brave Men” and “Emotional Women”, researchers concluded that pain experienced by women was often described as medically inexplicable, as there was often no visible cause for their pain. As a result, healthcare professionals often attributed the pain to a psychological rather than physical cause. This was due to the absence of any visible or diagnostic evidence of illness.
Studies have found that in addition to medical professionals assuming that women have higher pain thresholds, there is also an assumption that they are more emotionally unstable. Research published in 2001 found that when women came to their doctors with legitimate concerns of chronic pain, they were more likely to be described as “emotional”, and their pain to be “psychogenic”, and “not real” by their medical expert. This is especially harmful for endometriosis patients who already face long diagnosis waiting periods and may not feel like they’re listened to.
The gender health gap, especially as it relates to endometriosis, has historical roots in medical practice. Endometriosis.org explains that pain associated with endometriosis is often dismissed because “‘women’s problems’ perplexed nineteenth-century doctors, who saw them as indicative of unstable and delicate psychological constitutions. Even though attitudes […] have improved during the twentieth century, some of the old beliefs still linger unconsciously, and affect the medical profession’s attitudes towards complaints including period pain.”
In 2014, Brigham and Women’s hospital in the U.S. said that medical developments that look into the way conditions are treated and diagnosed “routinely fail to consider the crucial impact of sex and gender. This happens in the earliest stages of research when females are excluded from animal and human studies or the sex of the animals isn’t stated in the published results.” This would suggest that in order to tackle the gender health gap and improve medical understanding of conditions like endometriosis, medical research that includes and prioritizes the experiences of people who identify as women need to take place in higher numbers.
The lack of medical research on endometriosis leads to less medical education on the disease, and can result in serious delays in the period of time it takes to receive an endometriosis diagnosis and how much your doctors understand about the condition.
Many women with endometriosis who have gastrointestinal symptoms are often misdiagnosed as
- Inflammatory bowel disease
- Crohn’s disease
If symptoms are cyclical in nature, it’s a sign indicating endometriosis. Some women may have symptoms throughout the cycle in chronic cases but the symptoms do aggravate during menstruation
Origin of Endometriosis
The origin of endometriosis is still not well defined. Many hypotheses have been proposed to explain the development of endometriosis and Dr David Redwine has proposed the most viable theory – Mulleriosis – that appears to cover all the salient features of endometriosis. His theory favours a genetically-driven embryonic origin of endometriosis. Müllerian tissue is tissue in a female embryo that eventually develops into the fallopian tubes, uterus, cervix and the upper part of the vagina. Mulleriosis indicates a problem of differentiation and migration of any Mullerian tissue during the formation of the embryo which results in patches of this tissue being laid down in abnormal locations in the pelvis or elsewhere in the body. Later in life, these misplaced patches of tissue develop into endometriosis when they are exposed to oestrogen.
To support his theory, Dr Redwine described a case of fingertip endometriosis, where surgical excision brought complete relief. He posits that that’s because the entire tract of Mulleriotic tissue that had been laid down in the dermis or nail bed had been removed by excision.
Via Dr David Redwine:
The cause of endometriosis is a subject of continued debate. My best guess is that it is a disease that the woman is born with because of a process called embryologically patterned metaplasia. At the moment of conception, a woman is dealt three cards.
- The first card is that she will have endometriosis.
- The second card is where in her body the disease will be.
- The third card is how biologically active the disease will be in each area.
And depending on these various cards, which can be quite different from patient to patient, endometriosis, or areas that will become endometriosis, are laid down in the woman’s pelvis or elsewhere in the body during foetal formation. When oestrogen production begins at puberty, the tracts of tissue that were laid down can become painful and can begin to change into endometriosis. Men can also develop endometriosis for somewhat the same reasons.
Excision is the only cure
Going by Dr Redwine’s theory, excision of the lesions is the only cure for endometriosis, however it needs to be done by a surgeon who is specialised at removing the lesions ‘from the root’ otherwise they will grow back. The recurrence of endometriosis after ovarian endometrioma excision has been evaluated at 24, 36, 60, and 120 months as 5.8%, 8.7%, 15.5% and 37.6% respectively.
Development and Progression of Endometriosis
Endometriosis is driven by oestrogen that may come from the ovaries or from within the lesions themselves. Women with endometriosis tend to to have higher ovarian production of oestrogen and this combined with lesional oestrogen can result in high levels that make symptoms worse.
The central driver connecting oestrogen to symptoms is the high production of prostaglandin E2 (PGE2). PGE2 is a regulator that makes the environment inside the body more favourable for endometriosis to develop and progress by affecting various cellular activities and immune responses. Specifically, it:
Feedback loop between oestrogen and PGE2 promotes growth and inflammation
Two basic pathologic processes, namely growth and inflammation, are responsible for chronic pelvic pain and infertility, which are the primary devastating symptoms of endometriosis. Estrogen enhances the growth and invasion of endometriotic tissue, whereas PGE2 and cytokines mediate pain, inflammation and infertility.
Estradiol (E2) is produced locally in endometriotic tissue. The precursor, androstenedione of ovarian, adrenal or local origin becomes converted to estrone (E1) that is in turn reduced to E2 in endometriotic implants.
Endometriotic tissue is capable of synthesising androstenedione from cholesterol via the activity of steroidogenic acute regulatory protein (StAR) and other steroidogenic enzymes also present in this tissue. E2 directly induces cyclo-oxygenase-2 (COX-2), which gives rise to elevated concentrations of PGE2 in endometriosis. The cytokine Interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF) and PGE2 itself are also potent inducers of COX-2 in uterine cells. PGE2, in turn, is the most potent known stimulator of StAR and aromatase in endometriotic cells. This establishes a positive feedback loop in favour of continuous oestrogen and PG formation in endometriosis.
Feeding into this loop is arachidonic acid which is synthesised from omega-6 fats commonly found in foods. COX-2 converts arachidonic acid to to PEG2 which directly increases COX-2, creating another feedback loop.
PEG2 increases the rate of the enzyme aromatase, increasing E1, and because the enzyme 17β-HSD is low in edometriotic tissue, this then increases the production of E2.
Women with endometriosis produce more lactate which stimulates an environment that promotes invasion of endometrial cells into the peritoneum so that they form lesions.
PGE2 prevents the macrophages of the immune to do a clean up job
Abnormal hormone production by endometriotic lesions is a significant factor that helps endometriotic tissues survive and grow. However alongside this is a critical issue in immune system dysfunction, particularly the reduced ability of immune cells to consume and remove unwanted materials, a process known as phagocytosis. This dysfunction is largely due to macrophages, a type of immune cell responsible for cleaning up debris, not working properly.
In cases of endometriosis, these macrophages are attracted to the peritoneal cavity, an area inside the abdomen, because of inflammation. Ideally, they should remove abnormal endometrial tissue that is present in the peritoneal cavity. However, they often fail to do this effectively in endometriosis, allowing the endometriotic tissue to grow.
The way macrophages function involves two main methods. Firstly, they produce zinc-based enzymes called matrix metalloproteinases (MMPs) to break down the surrounding material of foreign entities. Secondly, they use scavenger receptors (CD36) to enhance the uptake and destruction of cell debris. In endometriosis, however, the function of these macrophages is impaired. In the presence of a high concentration of PGE2, the expression of MMP-9 and CD36 is suppressed. This significantly inhibits the phagocytic ability of macrophages. As a result, the endometrial tissues proliferate in the peritoneal cavity, maintaining and progressing endometriosis.
In essence, the development of endometriosis is not just about the abnormal production of hormones by the lesions but also involves significant dysfunction in the immune system, especially in macrophages. This dysfunction is characterised by a reduced capacity to remove unwanted materials and impaired production of important enzymes and receptors, influenced by PGE2 in the peritoneal fluid.
PGE2 is the likely master of endometriosis
In women with endometriosis, there are two self-reinforcing cycles that keep the levels of PGE2 high in the peritoneal fluid.
In essence, elevated PGE2 in the peritoneal fluid maintains a cycle that encourages the development and persistence of endometriosis by influencing increased hormone production and cell proliferation, and immune cell dysfunction.
Additional sources of inflammation
Interactions with gut bacteria, blood debris, iron overload, anti-oxidant deficiencies, increased nitrites/nitrates and gene expression of oestrogen metabolism also play a part in maintaining endometriosis.
Disrupting the feedback loops, reducing PEG2 and supportive anti-oxidants are effective treatments for endometriosis
Understanding the biochemical pathways involved in the maintenance and progression pf endometriosis provides targets for interventions to reduce and manage inflammation and lesion growth.
Arachidonic acid inhibitors
- EPA:GLA ratio of 8:1
Essential fatty acids (EFAs) are biologically active fats which the body requires to support several important functions from blood clotting to inflammation; differentiating them from other fats which are either stored or used for energy. EFAs are deemed ‘essential’ because humans and other animals cannot produce them; meaning that they must be consumed from food.
The two types of fatty acids which are essential to the body are omega-3 (ALA) and omega-6 (LA). Other fatty acids such as EPA, DHA and GLA are considered ‘conditionally essential’ as they may become essential under certain developmental or disease conditions.
Arachidonic acid, derived from LA is found in meat, eggs and dairy, and is needed to support muscle growth, brain development and a healthy nervous system. However, we only require very small amounts of this fatty acid and when consumed in excess, it can promote inflammation.
Human studies have revealed that when EPA is introduced in a balanced ratio to GLA, elevations in serum arachidonic acid are prevented leading to a reduction in levels of pro-inflammatory PGE2. This conversion requires adequate zinc, magnesium and vitamin B6 as cofactors.
The ideal ratio of EPA to GLA to suppress arachidonic acid is 8:1 and should be combined with the cofactors.
Quercetin is found many fruits and vegetables including citrus fruits, apples, onions and strawberries, and is known to reduce inflammation. It does this by interfering with the production of arachidonic acid. Specifically, quercetin stops the creation of inflammatory mediators like PGE2 and leukotrienes. These mediators are not only involved in causing inflammation but also play a role in controlling how the uterus contracts. Quercetin has been shown to significantly reduce endometrial lesions.
IL-1, VEGF and oxidative stress inhibitors
- Vitamin B1 (thiamine) can reduce excess lactate made from malfunctioning mitochondria which upregulates PEG2, and reduce the pain of endometriosis. A deficiency of thiamine has been found to promote endometriosis. Dr Derrick Lonsdale prefers Lipothiamine (TTFD), although Benfotiamine has been found to reduce arachidonic acid in macrophages.
- Melatonin, which induces sleep, has been shown to inhibit the conversion of cholesterol to androstenedione, thereby decreasing the amount available to be converted to oestradiol. A Phase 2 randomised clinical trial involving 40 women with endometriosis, ages 18 to 45 showed that melatonin treatment significantly reduced endometriosis-associated chronic pelvic pain and improved sleep quality without having to use a painkiller. Digital devices such as laptops, smartphones, and tablets generate blue light that can inhibit the natural production of melatonin.
Reducing systemic oestradiol (from the ovaries, gut and adrenals)
There has been extensive data over the past decades indicating endometriosis may be linked to select co-morbid conditions in some individuals with the disease as well, including but not limited to a low/modest association between certain pigmentary traits and melanoma; pain syndromes (interstitial cystitis/painful bladder syndrome, irritable bowel syndrome/inflammatory bowel disease, chronic headaches, chronic low back pain, vulvodynia, fibromyalgia, temporomandibular joint disease, chronic fatigue syndrome, etc.) as well as mood conditions (defined as depression and anxiety) and asthma; select infections and endocrine disorders; headaches and migraines; thyroid disease and others. Similarities in the clinical and epidemiological features of the associated disorders may be at the root of their co-morbidity, and further investigation is needed.
There is a very strong association with many autoimmune diseases and endometriosis, Hashimoto’s thyroiditis probably being the most prevalent, as well as lupus, antiphospholipid syndrome, scleroderma and multiple sclerosis. 3 common gene fingerprints – known as haplotypes – are prevalent with women with endometriosis. One of these haplotypes accounts for about 90 percent of all autoimmune disease an includes celiac disease, which is why cutting out gluten can have a tremendous benefit symptomatically (see the section on interventions for dietary recommendations).
The other haplotypes are associated with antiphospholipid syndrome, Hashimoto’s thyroiditis, autoimmune hepatitis and are antibody mediated. The antibodies can react to paternal antigens in pregnancy and can lead to pregnancy loss. This may be a cause of repeated miscarriages and multiple IVF failures, and may point to ‘silent endometriosis’ where endometriosis exists, but does not present with any of the common symptoms.
Endometriosis is often associated with Restless Leg Syndrome (RLS) an irresistible urge to move the legs due to an unpleasant non-painful sensory disturbance, described in a variety of ways for example as crawling, creeping and pulling. RLS is associated with dopamine deficiency. Dopamine is a neurotransmitter which mediates multiple functions in the body and its deficiency is associated with
- low moods
- lack of motivation
- inability to experience pleasure
- trouble getting going in the morning
- mood swings
- memory loss
- inability to focus and concentrate
- inability to connect with others
- low libido
- sugar cravings
- caffeine cravings
- inability to handle stress
- inability to lose weight
Research shows that women with moderate to severe endometriosis have a higher than normal frequency of genes which show mutations – polymorphisms – in dopamine receptors – dopamine receptor D2 (DRD2). The presence of polymorphism 2 could cause a defect in a post-receptor signalling mechanism, resulting in a mild increase in serum prolactin levels. Prolactin has angiogenic activity which may promote implantation of ectopic endometriosis tissue.
Studies with the dopamine agonist – a drug that promote a dopamine response – quinagolide, have shown a 69.5% reduction in the size of the lesions, with 35% vanishing completely. By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.
The use of high doses of dopamine agonists may cause an increase in the number of receptors that can make the post-receptor signalling mechanism work properly with this compensation, despite the presence of the polymorphism.
Contraindications for Endometriosis
Women with endometriosis should not use the copper coil because its side effects include longer, heavier and more painful periods.
Studies analysing the impact of hormone replacement therapy (HRT) for menopausal with endometriosis are conflicting, with some research showing that oestrogen therapy could reactivate endometriosis. A systematic review of the literature suggested that the malignant transformation of the ectopic endometriotic tissue is related to oestrogenic stimulation. Women who are suffering with hot flushes, night sweats, brain fog, weight gain, anxiety and fatigue can reverse all these symptoms within 6 weeks with the Menopause Core Nutrition Solution.
My approach to Managing Endometriosis – A pain-free Life is Possible
The biggest breakthroughs in the management of endometriosis has come studies showing that nutrition, detoxification and supplements can effectively and significantly reduce pain and inflammation.
While there is no one-size-fits-all diet for endometriosis, there are certain foods that can exacerbate inflammation and make symptoms worse, and others that can help reduce inflammation and promote healing.
As an oestrogen-driven condition, nutrition has to focus on preventing excess oestrogen and other hormone intake. For this reason I recommend:
For lowering inflammation I recommend:
Include plants that help to detoxify oestrogen via the liver:
Gut and Vaginal Microbiome Restoration, and Detoxification
- Healing intestinal and vaginal microbiome imbalance and supporting liver detoxification restores hormone balance and remove sources of inflammation.
- For detailed lifestyle approaches (and additional discussion) please enrol on my free course, Endometriosis Explained
Endometriosis is a complex condition that involves immune dysregulation, inflammation, gut and microbiome imbalances, and a dominance of local and circulating oestrogen.
By Sandra Ishkanes
I am a Functional Medicine expert specialising in women’s hormonal health. I work like a health detective, rooting out the underlying causes of hormonal imbalances and I take a whole-body approach to healthcare, combining nutrition, supplements, lifestyle upgrades and cutting-edge biomedical testing.