2023-06-27 05:20:00
Up to 10% of women suffer from endometriosis (two million affected in Spain alone) and yet this disease is still shrouded in mystery. “It is as if we were making a puzzle, we are accumulating pieces, but we do not know what image we are looking for, we do not have a model that makes sense of everything,” explains Francisco Carmona, head of the Gynecology service of the Hospital Clínic from Barcelona. After treating this disease with surgery or hormonal treatments for decades, specialists like Carmona believe that in the coming years the understanding of the genetic causes of the disease or the integration of data that artificial intelligence will make possible can offer new alternatives to patients and a theory that helps to understand what you want to cure.
This disease occurs when the endometrial tissue, which covers the inside of the uterus and serves to house an embryo, grows where it should not. This tissue responds to the sex hormones produced by the ovaries and once a month thickens, preparing the woman for a possible pregnancy. That thickened and misplaced endometrium, in the ovaries, the pelvis and even beyond, causes the pain that many women associate with periods, can make sexual intercourse or the simple act of urinating painful, and is behind many cases of infertility.
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“Until not so long ago, the pain of menstruation was trivialized, by doctors, but also by women who, many times, in a disease with a hereditary component, had their mother as a menstrual referent, and told them that this pain is normal. That delayed diagnosis and treatment for years,” says Estela Lorenzo, a specialist at the Endometriosis Unit of the Hospital October 12 from Madrid. “That has changed especially for women. Doctors are much more interested because women demand more, they do not accept that period pain is normal, they demand to know the cause of their pain and a treatment, and they do not allow themselves to be treated condescendingly”, agrees Carmona.
However, adds Lorenzo, it will not only be necessary to change perception and attitude. “We do not have tests that allow us to detect the disease in its early stages. When we do an ultrasound and, even though they are much better, you may not see anything in a woman who is in pain. Now, in France, a diagnostic test in saliva has been approved that allows early detection. These types of minimally invasive and rapid tests are necessary”, explains Lorenzo, who also believes that the paradigm shift in recent years will change the treatment of endometriosis. “Before it was seen as a gynecological disease only, which was first local or pelvic, but now it is seen to have a systemic inflammatory component,” he continues.
A few days ago, the journal Science Translational Medicine posted a job of researchers from the University of Nagoya (Japan) who claimed that the presence of a type of bacteria could be behind some cases of endometriosis. In it, 155 women were analyzed, 79 of them with endometriosis and the rest without it. In 64% of the first ones, an infiltration of Fusobacterium was identified, a type of microorganisms that cause, among other things, periodontal diseases. Among healthy volunteers, that figure was less than 10%. According to the researchers, these bacteria would be behind the increase in transghrelin, a protein associated with endometriosis that would grow excessively due to the presence of a growth factor generated as part of the immune system’s response to infection. This mechanism was then tested in mice inoculated with Fusobacterium, which caused increased transghrelin and endometriosis-associated lesions. The scientists then gave the animals antibiotics to clear up the infection. With it, the problem of endometriosis was also reduced, something that, according to those responsible for the work, opens the door to using antibiotics as an alternative treatment to hormones in women with endometriosis.
“These results were very surprising, because we have treated many women with antibiotics and they have not improved. It is one more piece, it is provocative and interesting, but I would be prudent before concluding that antibiotics can be used to treat endometriosis”, says Carmona. Estela Lorenzo also raises the difficulty of establishing causality and recalls the anatomical differences between mice (which, among other things, do not menstruate) and humans. However, she acknowledges the importance of work like this in identifying the link between triggers of chronic inflammation, such as bacteria, and the origin of endometriosis. “It is possible that there are some genetically predisposed patients who initiate this inflammation by fusobacteria. There are many studies on the role of the microbiome in this disease, and we have examples of ailments such as ulcers, which were associated with stress before Helicobacter pylori was identified as the cause, or human papillomavirus and cervical cancer.” Lawrence exemplifies.
Endometriosis occurs when the lining of the uterus grows out of place, in places such as the ovaries, peritoneum, or intestine.getty
Carmona has more faith that clinical solutions to the disease “go through knowledge of genetics than through antibiotics.” This year, a collaboration of 25 scientific teams from around the world published the biggest study to date on the genetics of endometriosis. DNA analysis of 60,600 women with endometriosis and 701,900 who did not revealed, for example, a shared basis between endometriosis and other apparently unrelated painful experiences such as migraines or back pain. This is consistent with the observation by specialists that a woman can sometimes experience a lot of pain that does not correspond to the lesions seen on diagnostic imaging.
The authors of the work, which was published in Nature Genetics, propose that genetic predisposition may cause endometriosis to initiate inflammatory mechanisms that cause excessive sensitization of the central nervous system. This would cause pain to begin to be perceived with greater intensity in different parts of the body that have nothing to do with the initial endometriosis. Something that shows the complexity of this disease is that, in addition to this phenomenon, those pains in places far from the uterus that are repeated with menstruation can be the product of distant tissue implants, which, like a tumor cell, migrate from one organ to another. . “Implants in peripheral organs such as the sciatic nerve or pneumothorax associated with menstruation have been described, which are indeed due to a direct implantation of endometriosis,” says Lorenzo.
Carmona says that she has received an invitation to participate in an international project to find imaginative approaches that overcome the stagnation of the last 40 years in research to discover the origin of the disease and include new treatments. This initiative for endometriosis suggests that the lack of new solutions is due to the fact that almost all lines of work start from the same hypothesis. In this path of searching for alternative hypotheses, the Clinic researcher states: “There are combinations of genes that increase the risk of endometriosis, and detecting them early would prevent more serious phases from being reached. We can consider trying gene therapies if we discover that certain genes play a major role in the development of the disease, or adopt preventive or therapeutic strategies if we detect interactions between genetic factors and infections or in combination with specific types of environmental contamination that trigger the disease”. Add.
Returning to the analogy of the puzzle, Carmona assures that pieces continue to accumulate and that soon, perhaps not enough for women who suffer from the disease today, but very quickly in scientific terms, theories will appear that will change the understanding of endometriosis and its treatment. . “There is a combination of causes, genetic, epigenetic, environmental. We know that women who are born prematurely have a higher risk of endometriosis than those of normal weight, that women who were breastfed have less risk, there is a greater anatomical endometriosis in women who have suffered physical or psychological abuse, and progress is also being made in molecular tools to correct defects in hormone receptors associated with the disease. We have a lot of pieces to put together, we don’t even have a model yet, but I’m hopeful,” she concludes.
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