Endometriosis at its core is an inflammatory condition which influences and drives this insidiously complex condition.

Defined as the presence of endometrial-like tissue found outside of the uterus, endometriosis is responsive to a woman’s monthly cyclical hormonal fluctuations, causing inflammation and growth adhesions to neighbouring structures within the pelvic cavity. The tissue is termed endometrial lesions,¹ and can be found anywhere within the pelvic cavity, most commonly around the uterus, bladder, ovaries, fallopian tubes and bowel, but has also been found in more far-reaching organs such as the brain and lungs.² The build-up of lesions and subsequent scar tissue formation can affect fertility and functionality of associated organs.

Estimated to affect up to one in ten women,² endometriosis is usually accompanied by pain - on menstruation, intercourse, bowel movements and within the pelvic cavity, and additionally heavy bleeding. These symptoms are highly variable and an unreliable predictor of the severity of the condition.²

Key symptoms include:

Pain – during or after intercourse; on or around ovulation; at or around the onset of menses; with bowel movements; in the pelvic region, lower back or legs; on urination.

Bleeding – menorrhagia; irregular bleeding.

An inflammatory condition at its core

A higher than normal amount of circulating pro-inflammatory cytokines and disrupted interleukins patterns (IL-17, IL-6, IL-8, TNF-a and vascular endothelial growth factor, VEGF) are found within both the peritoneal fluid and plasma in patients with endometriosis.³ These inflammatory agents increase angiogenesis, critical for endometrial lesion proliferation and survival in the peritoneal cavity.³

Women with endometriosis have also been found to have significantly higher lipopolysaccharides (LPS) in the menstrual fluid and peritoneal fluid than non-sufferers.^4,5 The increase in LPS (i.e. endotoxins from gram negative bacteria) contributes to inflammation and increased endometrial lesion proliferation,⁵ a common feature of this disorder. It also links the co-morbidity with irritable bowel syndrome,⁶ which can affect up to 80% of endometriosis sufferers.¹

Further ‘fuel on the fire’ is the release of prostaglandins from the endometrium in response to progesterone withdrawal at the onset of menses. Researchers have found increased levels of prostaglandins in women suffering from endometriosis and dysmenorrhoea.⁷ Prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2) are proinflammatory omega 6 fatty acid metabolites, that increase uterine contraction and blood flow to the area and thus painful symptoms ensue. Cyclo-oxygenase 2 (COX2) expression is also stimulated by an increase in oestrogen levels, a strong mediator of inflammation.¹

On the other hand, prostaglandin E3 (PGE3) can reduce painful symptoms by modulating prostaglandin production and biochemical activity relating to pelvic pain.⁸

Note: Whilst endometriosis is subject to hormonal dysregulation and influence, the aim of this article is to look beneath the surface at the underlying driving inflammatory factors that then influence hormone infiltration and stimulation, exacerbating this condition.

Naturopathic treatment considerations

Naturopathic treatment options that focus on reducing inflammation, prostaglandins, and that target LPS, will reduce the proliferation of endometriotic lesions. This multifaceted naturopathic approach is a way to address these underlying drivers.

• Antimicrobial herbs, including phellodendron, that are rich in berberine may be helpful in downregulating LPS and act as effective agents against gram negative bacteria.⁹ Furthermore, berberine has been shown to downregulate LPS-induced endotoxaemia by reducing injury to intestinal epithelial tight junctions,¹⁰ further reducing inflammation.
• Curcumin, our go-to anti-inflammatory herb: curcumin’s ability to inhibit inflammatory enzymes, COX2, LOX and suppress prostaglandin synthesis has been well documented.¹¹ Researchers have shown curcumin to exhibit antioxidant effects, reduce inflammatory cytokines and reduce progression of endometriosis.¹² Curcumin was able to suppress the proliferation of endometrial cells by reducing oestradiol production within the endometrium.¹³
• For the benefits of increasing dietary omega-3 fatty acids, a large study discovered a risk between trans-fat intake and increased risk of endometriosis, whereas those on a higher omega-3 rich diet had a lower risk.¹⁴ The EPA:AA ratio may be indicative of the severity of endometriosis.¹⁵ In a mouse model, the anti-inflammatory effect of omega-3 fatty acids was found to suppress endometrial lesion formation within the peritoneum.¹⁶ 
• An honourable mention must go to N-acetylcysteine (NAC). NAC has shown favourable results in studies. Well-known for its ability in reducing reactive oxygen species, downregulating inflammation by ameliorating toxic by-products, NAC may reduce endometrioma mass, tissue inflammation and cell invasiveness.¹⁷ A study of 73 women prescribed 600mg NAC three times a day for three consecutive days a week, showed a reduction in endometrial lesion or cyst size and reduced pain, with almost half of the NAC treated women cancelling their scheduled laparoscopy, and many became pregnant.¹⁸

Endometriosis a mosaic condition

Endometriosis is a complex, multifactorial and often debilitating condition. It affects fertility, mental health and has significant cost financially and mentally on the sufferer. Fortunately there are numerous natural treatment options available to support patients suffering from this debilitating condition.

References

1. Trickey, R. Women, hormones and the menstrual cycle. Third edition. Victoria: Trickey Enterprises; 2011. Chapter [13], Endometriosis and Adenomyosis; p [252].
2. Endometriosis Australia. Downloads: Facts. 2014. Available from: https://www.endometriosisaustralia.org/endometriosis-facts
3. Ahn SH, Edwards AK, Singh SS, Young SL, Lessey BA, Tayade C. IL-17A contributes to the pathogenesis of endometriosis by triggering proinflammatory cytokines and angiogenic growth factors. The Journal of Immunology. 2015 Sep 15;195(6):2591-600.
4. Khan KN, Kitajima M, Inoue T, Fujishita A, Nakashima M, Masuzaki H. 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis. Reprod Sci. 2015;22(5):585-94.
5. Khan KN, Fujishita A, Hiraki K, Kitajima M, Nakashima M, Fushiki S, Kitawaki J. Bacterial contamination hypothesis: a new concept in endometriosis. Reproductive medicine and biology. 2018 Apr;17(2):125-33.
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10. Gu L, Li N, Gong J, Li Q, Zhu W, Li J. Berberine ameliorates intestinal epithelial tight-junction damage and down-regulates myosin light chain kinase pathways in a mouse model of endotoxinemia. Journal of Infectious Diseases. 2011 Jun 1;203(11):1602-12.
11. Aggarwal BB, Surh YJ, Shishodia S, editors. The molecular targets and therapeutic uses of curcumin in health and disease. Springer Science & Business Media; 2007 Aug 6.
12. Swarnakar S, Paul S. Curcumin arrests endometriosis by downregulation of matrix metalloproteinase-9 activity.
13. Zhang Y, Cao H, Yu Z, Peng HY, Zhang CJ. Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iranian journal of reproductive medicine. 2013 May;11(5):415.
14. Missmer SA, Chavarro JE, Malspeis S, Bertone-Johnson ER, Hornstein MD, Spiegelman D, Barbieri RL, Willett WC, Hankinson SE. A prospective study of dietary fat consumption and endometriosis risk. Human Reproduction. 2010 Mar 23;25(6):1528-35.
15. Khanaki K, Nouri M, Ardekani AM, Ghassemzadeh A, Shahnazi V, Sadeghi MR, Darabi M, Mehdizadeh A, Dolatkhah H, Saremi A, Imani AR. Evaluation of the relationship between endometriosis and omega-3 and omega-6 polyunsaturated fatty acids. Iranian Biomedical Journal. 2012 Jan;16(1):38.
16. Tomio K, Kawana K, Taguchi A, Isobe Y, Iwamoto R, Yamashita A, Kojima S, Mori M, Nagamatsu T, Arimoto T, Oda K. Omega-3 polyunsaturated fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models. PloS one. 2013 Sep 10;8(9):e73085.
17. Pittaluga E, Costa G, Krasnowska E, Brunelli R, Lundeberg T, Porpora MG, Santucci D, Parasassi T. More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis. Fertility and sterility. 2010 Dec 1;94(7):2905-8.
18. Porpora MG, Brunelli R, Costa G, Imperiale L, Krasnowska EK, Lundeberg T, Nofroni I, Piccioni MG, Pittaluga E, Ticino A, Parasassi T. A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine. Evidence-based Complementary and Alternative Medicine. 2013;2013.