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“Endometriosis is not a hormonal condition. It’s affected by oestrogen, but is not caused by oestrogen or oestrogen dominance.”
Lara Briden

Endometriosis is a chronic, painful female health condition that can significantly affect quality of life and fertility. There is no single known cause - it is a complex health problem, the exact pathogenesis and pathophysiology are still unclear and there are a wide range of possible contributing factors. There is also no singular protocol to follow; just as with any other complex health problem, a functional medicine approach requires the individual to be placed right at the heart of any endometriosis support plan.

In this article we take a closer look at 7 underlying factors which may contribute to endometriosis and share some key considerations on how you may help to support these naturally.

What is endometriosis?

Endometriosis is a common female health problem which is estimated to affect around 15% of all women. It mainly affects women of reproductive age and happens when parts of the endometrium migrate outside of the womb and implant into other areas such as the ovaries, pelvis, bladder, bowel and fallopian tubes.

Even though these endometrial implants are located in the wrong places, they are still responsive to the hormone changes that happen during the course of a normal menstrual cycle. And at the end of the cycle when bleeding occurs, these endometrial patches bleed too.

In a normal period, blood exits the body via the vagina, however there is no available outlet for the endometrial patches that implant outside of the womb; instead the blood becomes trapped causing pain and inflammation, and this can eventually lead to cysts and scar tissue.

Signs and symptoms of endometriosis may include heavy, irregular or painful periods, generalised pelvic pain, gastrointestinal problems, fatigue, nausea, back pain, painful intercourse and fertility problems.

Endometriosis – 7 Key factors to consider

1. Immune dysfunction
We know that endometriosis happens when endometrial tissue is implanted from retrograde menstruation, however retrograde menstruation happens in nearly all women so it is clear that other factors must be involved. Current evidence supports the involvement of immune cells in the pathogenesis of endometriosis.1,2 And whether they are involved in the initial cause, or stimulate actions that enhance disease, it is widely agreed that there is at least some level of immune dysfunction in endometriosis. There is now much debate on whether endometriosis should be more accurately classified as an autoimmune disease.3,4

Natural support considerations:
• Vitamin A
• Vitamin D3
• Zinc citrate or picolinate
• Plant sterols

2. Impaired inflammation resolution
We need inflammation; it is a critical process for our survival, but we also need inflammation to subside when it is no longer needed. This phase is called inflammation resolution - where acute inflammation abates, tissues are repaired, cellular debris is cleared and homeostasis is restored. Inflammation resolution is vitally important to prevent the switch from acute to chronic inflammation and scientists have found that impaired resolution may well be a significant factor underlying common chronic health problems characterised by chronic inflammation and pain such as endometriosis. Specialised pro-resolving mediators (SPMs) are lipid mediators derived from polyunsaturated fatty acids (particularly omega-3s) that actively coordinate the resolution of inflammation. SPMs are often referred to as inflammation’s ‘stop signals’ and patients with endometriosis have been found to have reduced levels of SPMs in endometriotic tissues.5

Natural support considerations:
• Omega-3s enriched with SPMs

You can read more about SPMs & inflammation resolution here.

3. ‘Bacterial contamination hypothesis’
More recently, a new concept called the ‘bacterial contamination hypothesis’ has been proposed in endometriosis. In a 2018 study published in Reproductive Medicine and Biology researchers found menstrual blood in endometriosis sufferers to be highly contaminated with Escherichea coli and endometrial samples were colonised with other microbes.6 They also found that lipopolysaccharide (LPS) regulates the pro-inflammatory response in the pelvis and growth of endometriosis via the LPS/ Toll-like receptor 4 (TLR4) cascade and observed a cross-talk between inflammation and ovarian steroids or the stress reaction in the pelvis. They concluded that, “as an inflammatory mediator, lipopolysaccharide (LPS) could be the initial trigger and bacterial contamination its source in the intrauterine environment that could be the primary cause in the growth regulation of endometriosis, either alone or in combination with ovarian steroids or a tissue stress reaction in the pelvis.” The full research paper is well worth a read if you want a deeper dive into this subject.

Natural support considerations:
• Probiotics (Lactobacillus acidophilus NCFM® & Bifidobacterium lactis Bi-04®)
• Berberine
• Iodine

4. Sub-optimal nutrition
Optimal nutrition sits right at the foundation of health overall and anything ranging from sub-optimal intakes to full blown nutrient deficiencies have the potential to influence the initiation and progression of chronic health problems including endometriosis. Poor nutrition may result in changes in lipid metabolism, oxidative stress, immune alterations, poor methylation, lowered stress resilience, impaired detoxification capacity and epigenetic alterations to name but a few ways that nutrient status may be involved in the initiation or progression of endometriosis.7 Optimising nutrient intake is a key consideration for individualised endometriosis support.

Natural support considerations:
• High strength daily multivitamin & mineral supplement

5. Oxidative stress
Evidence suggests that oxidative stress is an important factor in both the pathogenesis and the pathophysiology of endometriosis. Supporting the body’s endogenous production of antioxidants in addition to optimising consumption of dietary antioxidants is key.7

Natural support considerations:
• Broccoli extract (glucoraphanin) & mustard myrosinase
• N-Acetyl Cysteine
• Glutathione

6. Oestrogen
Endometriosis may not be caused by oestrogen but we do know that it is affected by oestrogen. The term oestrogen describes not just one hormone but rather a group of oestrogens (oestrone (E1), oestradiol (E2) & oestriol (E3)). These hormones are made, utilised, metabolised, detoxified and finally excreted by the body and alterations at any stage in this complex process can influence endometriosis. By way of just one example, aromatase is a key enzyme for the biosynthesis of oestrogen. There is no aromatase activity in normal endometrium, however endometriosis tissue contains very high levels of aromatase enzyme, which leads to the production of high levels of oestrogen. Prostaglandin E2 – one of the best known mediators of pain and inflammation has been found to induce aromatase enzyme and the formation of local oestrogen in endometriosis tissue.8 And it’s not just endogenous oestrogen production that’s a factor; we are exposed to xeno-oestrogens from our food, water, home and external environments, all of which add to the total oestrogen load that the body must deal with. Whilst the relationship between oestrogen and endometriosis is complex, the good news is that there are many ways you can positively influence it.

Read more about this here in our oestrogen balance support guide.

Natural support considerations:
• B6, B12, 5-Methyltetrahyrdofolate (5-MTHF)
• Zinc citrate or picolinate
• Magnesium glycinate
• Broccoli extract (glucoraphanin) & mustard myrosinase
• Calcium D-Glucarate
• Indole-3-Carbinol
• Diindolylmethane (DIM)

Read more about the different benefits of sulforaphane, indole-3-carbinol (I3C), calcium D-glucarate and diindolylmethane (DIM) here.

7. Chronic stress
Chronic stress has the potential to impact every aspect of health and thus it will come as no surprise that it is a critically important factor to consider for endometriosis too. There are now well established links between Adverse Childhood Events (ACEs) and auto-immunity.9 Just dealing with and managing the condition itself can be traumatic and a significant source of ongoing stress – and as with many chronic health problems, it’s easy to then become trapped in a vicious cycle. Whilst lifestyle changes and key nutrients and botanicals may be helpful in calming the stress response and promoting resilience, it is difficult to overestimate the importance of talking therapies as part of a support plan when chronic stress has been identified as a key factor. It is also essential to consider the ‘stress’ of dietary and lifestyle changes too, to tread carefully and pace recommendations to match where clients are at.

Natural support considerations:
• Magnesium glycinate
• Vitamin C
• Asian ginseng root extract, Rhodiola rosea, Cordyceps sinensis extract
• Ashwagandha (KSM 66®)


Find out more:
Read More About Diet, Lifestyle And Supplement Considerations For Endometriosis Here
Watch Jo Gamble’s Webinar On Female Health: Endometriosis And Fibroids Here
Read Our Endometriosis Protocol Here


References:
1. Izumi G, Koga K, et al. Involvement of immune cells in the pathogenesis of endometriosis. J Obstet Gynaecol Res. 2018 Feb; 44(2): 191-198
2. Vallve-Juanico J, Santamaria X, et al. Macrophages display proinflammatory phenothypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease. Fertility and Sterility. 2019 Dec; 112(6): 1118-1128.
3. Greenbaum H, Lugassy Galper BE, et al. Endometriosis and autoimmunity: Can autoantibodies be used as a non-invasive early diagnostic tool? Autoimmunity Reviews. 2021 May; 20(5): 102795
4. Zhang T, De Carolis C, et al. the link between immunity, autoimmunity and endometriosis: a literature update. Autoimmunity Reviews. 2018 Oct; 17(10): 945-955
5. Wu R, Zhou W, et al. Lipoxin A4 suppresses the development of endometriosis in an ALX receptor-dependent manner via the p38 MAPK pathway. British Journal of Pharmacology. 2014 Nov; 171(21): 4927-4940.
6. Khan KN, Fujishita A, et al. Bacterial contamination hypothesis: a new concept in endometriosis. Reprod Med Biol. 2018 Jan 18; 17(2): 125-133.
7. Halpern G, Schor E, Kopelman A. Nutritional aspects related to endometriosis. Rev Assoc Med Bras (1992). 2015 Nov-Dec; 61(6):519-23
8. Bulun SE, Fang Z, et al. Aromatase and endometriosis. Semin Reprod Med. 2004 Feb; 22(1): 45-50.
9. Dube SR, Fairweather DL, et al. Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med. 2009 Feb; 71(2): 243-50.

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