Endometrial tissue and endometriosis lesions: unravelling the connection

If you have a uterus and are of reproductive age, you have an endometrium. This is simply a term for the specialised layer of tissue that lines the inner cavity of the uterus like a plush carpet. Throughout the menstrual cycle, the endometrium thickens under the influence of the hormones oestrogen and progesterone, preparing a suitable environment for a potential fertilised egg. If pregnancy doesn't occur, the levels of progesterone decline, triggering the shedding of the endometrium – your menstrual period. It’s best to think about the endometrium as dynamic - it’s constantly undergoing changes throughout the menstrual cycle according to the signals of your body’s hormones.[2]

Endometrial tissue on the other hand is a broader term. It refers to the healthy lining of the uterus (the endometrium), but also to any tissue that shares similar properties but grows outside the uterus, which is what happens in endometriosis.

In a healthy situation for people without endometriosis, endometrial tissue will only grow within the endometrium, and this shedding and renewal process occurs exclusively within the uterus. You may hear a doctor refer to ‘eutopic endometrium’ - this simply refers to this endometrial tissue in the correct place - lining the inner cavity of the uterus.

Endometriosis lesions are abnormal growths of tissue that resemble the endometrium that lines your uterus. These lesions can also respond to the hormonal fluctuations of the menstrual cycle. They can thicken, break down, and can bleed just like the lining of the uterus. However, since they're located outside this area, the shed tissue and blood has nowhere to go. This can irritate surrounding tissues, leading to inflammation, pain, and scar tissue formation[3]. In other words, endometrial lesions are the physical manifestation of the condition we know as endometriosis.

It's important to note that while they resemble the endometrium, they are NOT the endometrium. There are several key differences between endometriosis lesions and healthy endometrial tissue.

One of the key differentiating factors between endometrium and endometriosis lesions is location. Endometriosis lesions develop outside the uterus, most commonly in the pelvic cavity, on the ovaries, fallopian tubes, and the tissues lining the pelvis. In some rare cases, they can even be found beyond the pelvic region including scars following surgery, the belly button and the chest, but these are less common.[4]

Endometriosis lesions also sometimes differ in cellular composition. They often contain a mix of cell types not typically found in normal endometrium, such as immune cells and altered mesenchymal stem cells (cells that develop into connective tissue, blood vessels, and lymphatic tissue). These changes contribute to the chronic inflammatory environment of endometriosis and the lesions' ability to invade surrounding tissues. [5] [6]

Another difference lies in gene expression. Endometriosis lesions often behave differently than the normal lining. In particular, genes involved in inflammation and immune response seem to be more active in these growths. Additionally, these lesions may not respond normally to hormones like estrogen and progesterone. This difference can affect how the growths behave and can explain why they might be resistant to treatments that involve hormones.[7] [8]

So, all endometrium is endometrial tissue, but not all endometrial tissue is healthy endometrium in the right place. Endometriosis lesions are abnormal growths of endometrial tissue, often in the wrong place that can behave differently to the healthy endometrium in your uterus.

‘Pathogenesis’ is simply a medical term for the process by which a disease or disorder develops. In this case, what many people diagnosed with endometriosis want to know is, what caused it? How and why do these lesions form? To answer this simply, we still don’t know the exact cause, though many different factors are thought to contribute to the condition. The below cover the most prominent[9][10]:

Retrograde Menstruation: This is the leading theory, proposing that menstrual blood containing endometrial cells backs up through the fallopian tubes and into the pelvic cavity. These misplaced cells then implant and grow on organs like the ovaries, intestines, or bladder.

While retrograde menstruation is common, not everyone who experiences it develops endometriosis.

Cell Transformation (Metaplasia): This theory suggests that cells lining the pelvic cavity undergo a transformation, changing into cells that resemble endometrial tissue. These transformed cells then start to grow and behave similarly to endometrial tissue during the menstrual cycle.

Embryonic Cell Misplacement: This theory proposes that during embryonic development, some endometrial cells get misplaced outside the uterus. These misplaced cells remain dormant until puberty when hormonal changes trigger their growth.

Stem Cells: Stem cells are versatile cells with the potential to develop into various cell types. Some researchers believe that certain stem cells might contribute to the development of endometriosis.

Bacterial Infection: One of the newest theories suggests that a Fusobacterium infection of the endometrium might contribute to endometriosis [11]

In addition to the above, immune phenomena,[12] genetics[13] and environmental[14] factors appear to play a role, and new research is emerging to confirm these connections and how exactly they may contribute.

While these theories offer potential explanations, it's likely that a combination of factors contribute to endometriosis, and might vary from person to person. The good news is that recent years have seen a surge in research around endometriosis.[15]

Given the similarity and complexity of the terms we’ve covered above it’s clear to see why the terminology that surrounds the condition can be confusing. If you have endometriosis, you have abnormal endometrial tissue that grows outside the endometrium, forming endometriosis lesions. Due to it being in the wrong place, and certain differences in the tissue, people diagnosed with the condition can experience symptoms including pain, inflammation and even scarring. If you are new to the endometriosis journey we encourage you to read the other articles on this site, including What is endometriosis? and What are the symptoms of endometriosis?

Endometriosis can be a complex and frustrating condition. Understanding some of the medical terms associated with it can be a powerful tool in navigating your diagnosis, treatment plan, and overall well-being. Firstly, it enables you to have more productive conversations with your doctor and to actively keep abreast of the newest research in the field. There is also a certain relief in demystifying your own condition so that you don’t feel overwhelmed by it, but rather feel empowered to manage it. Lastly, and perhaps most importantly it allows you to have a human conversation about it. Endometriosis is a condition that is largely invisible in our day-to-day lives, making it hard to really bring across the effect it has on your physical life and mental state to others. Being able to truly explain your condition to other people around you in an understandable way - including your partner, friends, family and even your workplace - is crucial to getting the support that makes living with endometriosis easier.