Clínica Fertia

The origin and evolution of endometriosis

In medical terms, to refer to the origin and evolution of a disease with all the factors that are involved in it, we talk about the ‘pathogenesis’ of said disease. In this post we are going to talk about the pathogenesis of endometriosis. Despite having been documented for the first time more than a century ago, to this day it continues to be an enigmatic disease.

What is endometriosis?

The term endometriosis refers to the presence of glands and stroma similar to the endometrial tissue that cover the uterine cavity located outside the uterus. First described by Rokitansky in 1860, who observed the presence of endometrial-like tissue invading the myometrium, and later Cullen described the presence of ovarian cysts and endometrial-like tissue in the rectus vaginal septum, it was Sampson (1) who coined the term endometriosis in 1927.

Theories about the origin of endometriosis.

Until now, the most accepted theory regarding its origin and development was Sampson’s theory of retrograde menstruation, according to this theory endometrial cells adhere to the peritoneum, establish blood flow, proliferate and produce endometrial implants.

This theory would explain that neonates who have menstruation at birth, especially postmature and with low weight (5% of all newborns) develop endometriosis in pre-menarche and adolescence. However, this theory does not explain the development of extragenital endometriosis, neither in women without an endometrium or even in men. Or the fact that even though most women experience retrograde menstruation, only one in 10 develops endometriosis.

In 1942, the theory of coelomic metaplasia was proposed, that is, the transformation of peritoneal and endometrial stem cells, or cells derived from the bone marrow or remnants of cells from the embryonic period into endometrial cells (2). It is a reversible phenomenon and abnormal behavior due to an abnormal environment. This transformation does not imply transmissible genetic and epigenetic changes and therefore does not explain the hereditary nature of this entity. It must be remembered that blood relatives have a 6-9% risk of suffering from the disease and up to 15% of suffering severely from the disease. Hereditary factors are believed to be involved in half of all cases of endometriosis.

Recently, the theory of genetic and epigenetic changes has been developed (3) that can explain many of the findings in this entity. Epigenetics refers to genetically transmissible changes caused by environmental and external factors that do not imply a change in the DNA sequence. These changes can range from endometrial cells to stem cells. We know that the oxidative stress that occurs during retrograde menstruation is capable of inducing epigenetic changes, as well as changes in the uterine and peritoneal cavity microbiome; some incidents develop during the intrauterine stage and others throughout life (dioxins, radiation, pollution, oxidative stress …). The cumulative effect of these incidents is required, which are transmitted from one cell to another from one generation to another and which makes the cells more vulnerable to new incidents and this accumulation will be the one that gives rise to the development of the disease in its various presentations, typical, cystic, deep and extragenital endometriosis (4).

Once the injury occurs, it develops in an environment other than the uterine with a different microbiota, endocrine and paracrine immunological factors. Cyclical hormonal changes with eventual bleeding leads to repeated microtrauma that increases the risk of genetic and epigenetic incidents and development of fibrosis and disease progression. Due to this, many of the immune and endometrial changes associated with endometriosis have to be considered a consequence of this genetic predisposition rather than a consequence of endometriosis.

 On the other hand, epigenetic changes are potentially reversible, although it is more difficult when various epigenetic incidents are associated. This potential reversibility would explain why the presence of microscopic endometriosis has no clinical translation and why incomplete excision of deep endometriotic lesions is not associated with a higher risk of recurrence compared to large resections. These observations suggest that cells with reversible epigenetic changes return to normal when the motor of these incidents is respected, as in the case of the resection of a deep endometriotic nodule and explain the diverse response to different medical treatments.

Knowledge of the various mechanisms involved in the development of this disease will allow us to develop better strategies for its prevention, diagnosis and treatment. Trying to prevent incidents that trigger epigenetic changes, such as reducing oxidative stress caused by retrograde menstruation, improving the microbiota and preventing pelvic inflammatory disease, can be a starting point.

 Endometriosis affects 10% of women and is present in 35% of infertile women. In our fertility clinic we are specialized in highly complex cases that this pathology presents. Our team is always updating and following the most recent studies on endometriosis in order to offer cutting-edge treatments that help our patients fulfill their dream of becoming mothers.

 If you are finding it difficult to get pregnant, we encourage you to book your first visit at our clinic so that you can tell us about your case personally and find out how we can help you.



  1. Sampson JA. Peritoneal endometriosis due to menstrual disemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol.1927;14:422-469.
  2. Donnez J, Van Lagendockt A, Casanas-Roux F, Van Gossum JP, Pirard C, Jadoul P. Current thinking on the pathogenesis of endometriosis.Gynecol Obstet Invest.2002;54:52-58.
  3. Koninckx PR, Barlow D, Kennedy S. Implantation versus infiltration: the Sampson versus the endometriotic disease theory. Gynecol Obstet Invest.1999;47:550-556.
  4. Adamyan LV, Sptsyn VA,Andreeva EN. Comprenhensive monograph on etiology and pathogenesis of endometriosis from the standpoint of genetics. Moscow:geotar Media;2008.


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