Para leerlo en español, clic aquí.

Remember, the information on my website, podcast, Instagram, and any other ways I communicate and/or produce content is educational information only and not medical advice. Always check with your qualified medical professional before making any changes to your treatment plan for endometriosis or any other health problems. See my full disclaimer here.

Endometriosis Biology

Endometriosis isn’t just tissue that shouldn’t be in the body. It’s a pain-inducing, estrogen-making, inflammation-generating tissue.

Here’s a simplified, bird’s eye overview of some aspects of what endometriosis does in the body, but keep in mind that there are pages and pages of research articles written about each of these concepts, which are much more complex than this.

Endometriosis isn’t a homogenous disease.

It has 3 generally accepted forms, and some people suspect that the different forms have different origins. Endometriosis can be a multitude of colors from clear to black and can be found in different locations throughout the body. Even more, on a biological level, lesions in the same person can have different characteristics!

Endometriosis is not the uterine lining.

Endometriosis is when tissue similar to the endometrium (the uterine lining) grows outside of the uterus. Endometriosis isn’t the uterine lining – it’s tissue that’s similar to it, but there are hundreds of differences between the two tissues including in the genes, hormone receptors, and enzyme expression. (1)

Endometriosis doesn’t slough and shed like a period.

Endometriosis does not slough and shed like a period. It’s commonly said endometriosis does this and then that blood has nowhere to go. This isn’t true. Endometriosis does not act like the uterine lining (the endometrium) because it’s not the uterine lining. In fact, there are hundreds of differences between the two tissues. While some endometriosis lesions may be associated with bleeding, including cyclically, it’s not having a mini-period.

“Endometriosis  doesn’t have a basalis layer and functional layer like the endometrium, so it does not slough and shed.” (Direct quote from Dr. David Redwine on my podcast interview with him).

Endometriosis can make its own estrogen via the aromatase enzyme (2)

Through various pathological processes, this can then drive inflammation and pain related to endometriosis.

It’s an important fact that endometriosis can make its own estrogen, because hormonal suppression is often given to people with endometriosis to lower their estrogen, sometimes to menopausal levels. However, these drugs affect the estrogen made by the ovaries (on the hypothalamo-pituitary-gonadal axis) and not the estrogen made via the aromatase enzyme (like the estrogen made by endometriosis). (3)

Endometriosis can have hormone receptors: estrogen, progesterone, both, or none.

The level and activity of the receptors can vary. This allows endometriosis to have a biological response to hormones, but it doesn’t respond to hormones in the same way that the endometrium does (because it’s not the endometrium).

Endometriosis can have progesterone resistance.

This means that the cells don’t respond to progesterone like they normally would. Through various pathological processes, this can contribute to inflammation, pain, and enhanced cell survival. (4)

Endometriosis is a chronic inflammatory disease that can cause local and systemic inflammation.

“Endometriosis can cause an activation of an innate immune response, increasing inflammatory and nociceptive cytokines/chemokines, growth factors, neutrophils, and prostaglandins.” (5)

NOTE: Endometriosis is not an autoimmune disease.

Inflammation is a central process in endometriosis and can lead to pain, remodeling of (changes to) neighboring tissues, fibrosis, adhesions, and infertility. (6)

Prostaglandins

Prostaglandins play a role in endometriosis pain and inflammation. This is why non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen may reduce pain in some people, because it blocks the COX enzyme, which is where prostagladins are mainly made.

“Estrogen is the inflammatory component of Endometriosis, which is why it is often called an Estrogen dependent disease. The Estrogen made at the lesion via the aromatase enzyme stimulates the release of excess prostaglandins (such as PGE2), which then creates an inflammatory response. The inflammatory response is simply a signal to the immune system that something is wrong. Unfortunately, our immune system isn’t able to destroy the Endometriosis lesions even though it is aware that it is there. While aromatase activation is incredibly complex, data suggests that PGE2 can stimulate the aromatase enzyme, thus creating more Estrogen at the lesion. This creates a never ending cycle.” [Thank you to Kate from EndoGirlBlog.com for this.]

Endometriosis is often associated with changes in the surrounding tissues that can lead to pain:

  • neovascularity (where completely new blood vessels form)

  • angiogenesis (where new blood vessels form from existing blood vessels)

  • neurogenesis (nerve growth)

  • neuroangiogenesis (the coordinated growth of blood vessels and nerves) (8)

Lesion inflammation can destabilize nearby capillaries, causing bleeding in the surrounding tissues.

Lesions can also become more fibrotic and deeper over time and invade into the surrounding tissue. (6) This can worsen symptoms or make them chronic.

Endometriosis and nerves

Nerves can be in or near the endometriosis lesions. Endometriosis can also trap or compress nerves, which can contribute to pain.

Neurogenic inflammation/ (Neuroinflammation)

In some endometriosis lesions, there are nerves in or near them. The inflammatory response to endometriosis from the immune system can also irritate or activate nerve fibers. These sensitized nerve fibers then release more pro-inflammatory mediators, and that inflammation starts the feedback loop over again by activating nerve endings. (9)

Feedback loop summary: Inflammatory mediators activate nerve endings -> nerves release pro-inflammatory mediators -> inflammatory mediators activate nerve endings (loop starts over)

Sources

Thank you to Kate from Endogirlblog.com for her help with finding these.

  1. Marquardt RM, Kim TH, Shin JH, Jeong JW. Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis? Int J Mol Sci. 2019 Aug 5;20(15):3822. doi: 10.3390/ijms20153822. PMID: 31387263; PMCID: PMC6695957.

  2. Nicola Pluchino, Ramanaiah Mamillapalli, Jean-Marie Wenger, Lauriane Ramyead, Panagiotis Drakopoulos, Jean-Christophe Tille, Hugh S. Taylor. Estrogen receptor-α immunoreactivity predicts symptom severity and pain recurrence in deep endometriosis. Fertility and Sterility, Volume 113, Issue 6, 2020, Pages 1224-1231.e1, ISSN 0015-0282, https://doi.org/10.1016/j.fertnstert.2020.01.036.
  3. Gheorghisan-Galateanu AA, Gheorghiu ML. HORMONAL THERAPY IN WOMEN OF REPRODUCTIVE AGE WITH ENDOMETRIOSIS: AN UPDATE. Acta Endocrinol (Buchar). 2019 Apr-Jun;15(2):276-281. doi: 10.4183/aeb.2019.276. PMID: 31508191; PMCID: PMC6711644.

  4. MacLean JA II, Hayashi K. Progesterone Actions and Resistance in Gynecological Disorders. Cells. 2022; 11(4):647. https://doi.org/10.3390/cells11040647
  5. Maddern J, Grundy L, Castro J, Brierley SM. Pain in Endometriosis. Front Cell Neurosci. 2020 Oct 6;14:590823. doi: 10.3389/fncel.2020.590823. PMID: 33132854; PMCID: PMC7573391.

  6. P Vigano, M Candiani, A Monno, E Giacomini, P Vercellini, E Somigliana, Time to redefine endometriosis including its pro-fibrotic nature, Human Reproduction, Volume 33, Issue 3, March 2018, Pages 347–352, https://doi.org/10.1093/humrep/dex354
  7. Wu MH, Shoji Y, Chuang PC, Tsai SJ. Endometriosis: disease pathophysiology and the role of prostaglandins. Expert Rev Mol Med. 2007 Jan 16;9(2):1-20. doi: 10.1017/S146239940700021X. PMID: 17227592.

  8. Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol. 2011;73:163-82. doi: 10.1146/annurev-physiol-012110-142158. PMID: 21054165.

  9. Matsuda M, Huh Y, Ji RR. Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth. 2019 Feb;33(1):131-139. doi: 10.1007/s00540-018-2579-4. Epub 2018 Nov 17. PMID: 30448975; PMCID: PMC6813778.