Development of endometriosis

Development of endometriosis: background, explanations and half-truths

Endometriosis is a gynecological disease that affects seven to 15 percent of women [1]. Endometriosis is one of the estrogen-dependent inflammatory diseases, i.e. an inflammatory disease that is controlled and influenced by the female sex hormone [2]. The causes of the disease have not been conclusively elucidated to date. There are five explanatory approaches that are being considered. However, experts today assume that several factors are involved in the development and onset of endometriosis.

Background: The most important facts about endometriosis

The term endometriosis is derived from the word endometrium. Endometrium is the technical term for the endometrium, i.e. the mucous membrane that is actually present exclusively in the uterus [3]. In endometriosis, however, tissue that behaves similarly to that of the endometrium appears outside the uterus and causes mild to severe symptoms in about two-thirds of affected women [1].

The disease endometriosis is characterized by the appearance of endometrial-like cells, cells that resemble those of the endometrium, outside the uterus. These accumulate in so-called foci, which consist of glands, stromal cells, smooth muscle and are traversed by nerve, lymphatic as well as blood vessels. Thus, it is not single cells, but real tissue with different cell types, blood supply and nerve cells [4]. The disease can occur without symptoms or with symptoms of varying severity and severity. It primarily affects women in the phase in which pregnancy is theoretically possible, but in exceptional cases it can also occur in prepubescent girls as well as postmenopausal women and very rarely in men [4].

In this article you will find information on the following topics:

Background knowledge about endometriosis
Overview of the different theories on the development of endometriosis
Myths and half-truths about endometriosis and how they should be classified

Endometriosis was first described in 1690 by the German physician Daniel Schroen, who dedicated his doctoral thesis to the topic “Disputatio inauguralis Medica de Ulceribus Uteri” (meaning: Medical discussion about ulcers in the uterus). The term endometriosis was coined by the American gynecologist John A. Sampson in 1920, and in 1927 he developed his origin model of the transplantation theory.

Pathogenesis: What are the causes of endometriosis?

Although endometriosis is a widespread disease that affects around two million women in Germany alone, the process of its development has not yet been conclusively clarified. [1,4].
There are currently five explanations for the way in which endometriosis develops [2]. However, none of these explanations alone can explain the different facets of the disease. Therefore, experts today assume that several factors together lead to the development of endometriosis.

Transplantation or implantation theory [2]

Transplantation medicine was developed by John A. Sampson in 1927, so it is the oldest theory. It is based on the assumption that menstrual blood is not only drained through the vagina to the outside, but also partially enters the abdominal cavity through the ovaries.

Even though this was not known back in the 20th century, it is now known, thanks to laparoscopies (abdominal endoscopies), that between 76 and 90 percent of women also secrete menstrual blood into the abdominal cavity during menstruation. Doctors then speak of so-called retrograde menstruation. This is therefore quite normal, yet not all of these women suffer from endometriosis.

In addition, this theory presupposes that the menstrual blood secreted into the abdominal cavity contains vital endometrial cells that can implant themselves in the abdominal cavity and be active there. This aspect has also now been demonstrated.

So it is possible that this is how the cells find their way.

However, some points cannot be explained by the implantation theory:

It does not explain why endometriosis occurs only in a fraction of women who menstruate retrogradely. It also fails to answer the question why endometriosis also occurs in rare cases in girls before their first menstruation and after menopause and even in men. In addition, this theory cannot explain how endometriosis lesions develop outside the abdominal cavity, for example in the lungs.

So the theory cannot be the whole truth.

Emergence from other cells on the spot

Coelom metaplasia theory [2] – Emergence from other cells with similar origin

According to this theory, developed around 1919 by Robert Meyer, endometriosis lesions develop from cells that lined the coelomic cavity during the embryonic phase. The coelomic cavity is the space containing the heart, lungs, digestive system and certain urogenital organs.

The cells of the body vary greatly in their specialization, but many have similar precursor cells from which they then further specialize to their final functions – also called differentiate. You could think of this like vocational training, changing the form, function, and appearance of cells as needed. The cells of the coelom develop further into cells of the genital organs but also into cells of the peritoneum or, for example, the digestive system.

The theory is that these cells, which have a common origin, re-evolve through inflammatory or hormonal influences into another type of cell with the same origin, in this case endometrial-like cells. This process is called metaplasia by experts. Existing cells thus transform into cells similar to endometrium. For example, under the particular influence of hormones such as estrogens and inflammatory processes.

This theory can also be used to explain the occurrence of endometrial foci outside the abdominal cavity, especially within the thoracic cavity (chest). The occurrence of endometriosis in women and girls before or after the reproductive phase, as well as in men, can also be explained with this theory.

The following aspects speak against this theory:

Metaplasia occurs with increasing frequency in older age. Endometriosis, however, decreases with age.
If one follows this theory, endometriosis should occur more frequently in men than is the case.

Induction theory

The induction theory is a further development of the coelom metaplasia theory and was developed by G. Levander and P. Normann in 1955. According to this theory, endometriosis lesions develop from undifferentiated cells, i.e. stem cells. Some stem cells are still present in tissues, even in adults. Triggers for the transformation of these unspecific cells into cells resembling those of the endometrium would be biochemical or immunological factors from the endometrium.

Animal experiments in rabbits have provided evidence that this theory is correct. Based on this theory, the menstruation-independent occurrence of endometriosis can also be explained. However, no stromal components could be detected in the tissue detected in the animal experiments. Endometriosis foci, however, possess stromal cells. Thus, the foci did not look quite the same in the experiment as they do in the clinic.

Embryonic remnant theory

The embryonic remnant theory was developed as early as 1890 by von Recklinghausen and Russel. According to this theory, endometriosis lesions develop from remnants of the so-called Müllerian ducts, i.e. from tissue from which the reproductive organs develop. This theory offers an explanation for the frequent occurrence of endometriosis in the area of the Douglas space. This is a pocket-shaped depression of the peritoneum between the rectum and the uterus. This theory also explains the frequent occurrence of endometriosis in women with Müller’s anomalies, i.e. malformations in the area of Müller’s ducts.

Even if the embryonic remnant theory can be supported by studies on embryos (autopsies after miscarriages or abortions), this theory cannot explain the occurrence of distant endometriosis lesions.

Development from other cells of the abdomen, from undifferentiated progenitor cells (such as stem cells), or from remnants of genital development, i.e., supernatant cells, is an explanatory theory.

Tissue-Injury and Repair Theorie [9]

Contrary to what was assumed for a long time, the uterus also has its own peristalsis, i.e. rhythmic muscular movement. Similar to the intestine, the uterus is also exposed to permanent mechanical stress. This constantly results in minute injuries to the tissue, so-called microtraumas. These occur mainly during strong contractions during the period. These injuries are continuously healed by repair mechanisms. During this repair mechanism, estrogens are released, which in turn activate peristalsis.

Just as there are people with increased intestinal peristalsis, there are also women with above-average uterine peristalsis. This results in increased microtrauma, which leads to an increase in uterine peristalsis via the release of estrogen in repair mode, and thus even more microtrauma. In addition, it is assumed that the lower number of pregnancies and thus increased number of menstrual periods also play their part in causing more micro-injuries.

Due to estrogen secretion and inflammatory processes, many micro-injuries can lead to changes in the endometrial cells. These then grow invasively into the uterine musculature and may also settle in the abdomen as a result of the change.

This theory is the most current theory, which is especially good at inferring adenomyosis. However, even it is not able to explain all aspects of endometriosis.

Lymphatic and vascular dissemination

This theory was developed by Halban (1925) and Sampson (1927), respectively. According to this theory, endometrial cells are carried by the blood or lymphatic route to distant tissues, where they settle and form endometriosis lesions. This theory has been confirmed by the fact that endometriosis cells have recently been found in both uterine veins and lymph nodes.

This theory can explain the development of endometriosis lesions in distant tissues. However, this theory also has its limitations: It cannot explain why women without a uterus or men can develop endometriosis in individual cases.

Development of endometriosis: other possible factors

As already mentioned, physicians today assume that a multitude of factors must coincide for endometriosis to develop. This is because none of the theories presented above can in itself offer a plausible explanation for the development of this disease in all its facets. These other triggering factors include in particular:

Iatrogenic carryover during surgery [1]
This is about endometriosis cells spreading to other parts of the body during surgery in the uterine area. This is not an explanation for the development of endometriosis. However, it could be an explanation for why endometriosis lesions can settle in some regions of the body. For example, scar endometriosis after cesarean section surgery in the cesarean section scar.
Molecular mechanisms [5]
Recent research shows that there are mechanisms at the molecular level that lead to deregulation, or alteration, of endometrial tissue. This has an impact on the growth, invasiveness and stem cell capacity of endometrial cells.
Hormonal changes [2]
It has been shown that the cells of endometrial foci lead to an increase in estrogen concentration. This in turn acts like an amplification on the development of endometriosis. Estrogen and progesterone concentration are of great importance for the development and growth of endometriosis [10] As a rule, increased estrogen concentration and decreased progesterone effect is responsible.
Genetics as well as epigenetics [2]
There is an increased risk among straight-line offspring of endometriosis sufferers to also develop endometriosis. Therefore, genes play a role in the development of endometriosis. However, external factors that lead to a change in the genes in the course of life also have an influence on the development and course of endometriosis.
Therefore, one speaks of a familial accumulation, but not of a direct heredity.

Myths and half truths

Certainly also because the causes of endometriosis are still not clear, numerous myths and half-truths surround the topic of endometriosis. These are likely to unsettle sufferers or to lead them hastily in the direction of a particular therapy. In most cases, there is a grain (or more) of truth to these myths, but it is used in the wrong context or misinterpreted. Here you will find the most important facts about common myths and half-truths:

You can’t get endometriosis without a uterus!
This is not true. People without a uterus, i.e. men, women with a malformation and women who have had a hysterectomy, are statistically far less likely to develop endometriosis. However, there are exceptional cases in which endometriosis also occurs in people without a uterus. And endometriosis can also come back after a hysterectomy. So if someone claims that without a uterus endometriosis would be gone or could not develop, this is simply wrong.
You can’t have endometriosis after menopause!
Endometriosis is most commonly diagnosed in women between the ages of 25 and 35. However, in exceptional cases, endometriosis is also found in women after menopause [6]. During menopause, estrogen concentration decreases in women, which has an impact on endometriosis. Therefore, it is often the case that endometriosis decreases or disappears completely during or after menopause [7].
However, it can still cause problems during menopause. Care should also be taken with the use of estrogen-containing agents to alleviate menopausal symptoms, because it is the drop in estrogen concentration that is responsible for hot flashes, for example, that is also responsible for alleviating endometriosis symptoms. And adhesions from operations also naturally remain during menopause.
But the good news is – during menopause, endometriosis actually gets much better for most!
Endometriosis can occur only after the first menstrual bleeding!
It is very rare for endometriosis to occur in girls before the onset of the reproductive phase. However, these cases do exist [4].
Endometriosis is a female-only disease!
Endometriosis affects almost only women. However, there are also a few men who develop endometriosis. This usually affects men who are treated with high doses of estrogen as part of treatment for prostate cancer.

You can’t get endometriosis with the “pill”!
The “pill,” or hormonal contraception, is actually used to treat endometriosis. Both some combined preparations and progestogen preparations significantly reduce the symptoms of endometriosis in most cases. However, taking the pill does not usually lead to a complete cure. In addition, the treatment success usually only lasts as long as the pill is taken [8]. It is therefore not a cure or a guarantee.

Resume:

Endometriosis is so widespread that in some cases it is already called a disease of civilization. Nevertheless, to this day the reasons leading to its development are not entirely clear. There are a number of theories. However, these can only ever explain partial aspects of the disease. Therefore, today experts assume that a variety of different factors are responsible for the development of endometriosis. These are: