There is a little-known disease, for which the causes are unknown and there is no cure, and almost no one talks about it. It is called endometriosis, and despite affecting 10% of women worldwide, when Professor Pietro Signorile (Martina Franca, Italy, 70 years old) did his residency in gynecology, he remembers that the textbook dedicated only three lines. “Now there are three pages, which are not few, but not enough either. There should be 30, but first we have to continue studying to know what we are talking about,” acknowledges this gynecologist, who has been in charge of the Italian National Endometriosis Center, the first of its kind dedicated to research into this still unknown disease. Author of numerous studies and patents to find a cure for this chronic ailment, Signorile talks about the importance of having a national center that centralizes research, something that is lacking in Spain.
Ask. When did you decide to dedicate yourself to studying endometriosis?
Answer. I dedicated the entire first part of my career to surgical oncology, operating on tumors of the female reproductive system. During those years I have had to do many terrifying, very devastating interventions to try to save the lives of my patients. We are talking about 40 years ago, when the systems that exist now did not exist and the interventions were high risk, with many complications and did not always have a positive result. After a couple of decades working in oncology under these conditions, I developed a kind of rejection towards this type of pathology. I wanted to change and I was fascinated by the fact that endometriosis was completely neglected both in specialist school textbooks and among doctors, patients and civil society in general. It remains that way.
Q. Why is it the great forgotten one?
R. This disease has been penalized for almost 90 years in research because of an incorrect theory by an American colleague, John Sampson. In 1927 he published the theory of retrograde menstruation as a cause of the disease, which said that the retrograde flow of endometrial waste flows backward through the fallopian tubes during menstruation into the peritoneal cavity. I have never believed in this theory, I have always fought it, but it has prevailed for decades and has delayed research.
Q. Because?
R. Due to a series of absurd evidence, which I can understand that in the 1920s would have made sense, but which in the 2000s continued to give credence, it was absurd. Firstly, because it has been discovered that retrograde menstruation affects almost all women in the world, almost 90%, while endometriosis affects only 10%. Research has wasted millions for decades with studies supposed to show why the remaining 80% did not suffer from endometriosis, without ever reaching a conclusion, because it was the wrong clue. Another proof is the fact that even women with Rokitansky syndrome, who are born without a uterus or tubes, have endometriosis, and at a higher rate than other women.
People, and doctors first, have to understand that it is a real disease, that it is not an invention
Q. There are many doubts when talking about this disease. Is there any certainty?
R. The solid certainty we have is that it is a congenital disease. A decade ago we reached this conclusion through a study on fetuses. Specifically, we are talking about a series of 101 female human fetuses that died at different times during gestation. And we discovered that 10% of these samples had endometrial tissue outside the uterus, which supports the hypothesis that it is a disease that manifests before birth.
Q. Why is it important that there be a national center?
R. To centralize research. In addition to the center, we also created the Italian Endometriosis Foundation, which has three objectives: research, patient support and clinical treatment. Despite not being a very large entity, it is a foundation that is dedicated exclusively to this, which is the only way for it to go from being a disease about which practically nothing was known to being able to find a cure. A full-time commitment is needed. The interesting thing would be to have a centralization of research, not only in Italy, but at a more global level, in such a way that another fifty years do not pass before new advances are achieved.
Q. What is the most urgent aspect of the investigation right now?
R. Without a doubt, speed up the diagnosis. In the countries of the European Union it takes approximately seven years to reach a diagnosis, and more than 7,000 euros are spent for each woman. This can not be. For every week, month and year that is lost, the quality of life of these women worsens dramatically. It must be understood that it is not a disease that affects only women, but rather concerns the entire society. Patients who suffer from it are up to three times more likely to develop ovarian tumor, and it also increases the risk of infertility. It is a family ailment.
Q. What are they doing in this regard at the foundation?
R. We have isolated proteins that are present in the saliva and blood of women with endometriosis, and we have generated a diagnostic test through saliva. We are about to begin the final validation phase at the Ministry of Health to be able to launch it. This would dramatically reduce wait times for a diagnosis. We have also managed to improve the examination through magnetic resonance imaging, because the disease is not always visible if you do not know exactly where to look. If it is in the organs, it cannot be seen even with surgery. For this reason, we have generated a specific contrast agent for endometrial tissue, which allows all tissues to be identified with MRI and is giving exceptional results. The next step is to focus on therapy, which is the most important thing for patients.
It takes approximately seven years to reach a diagnosis.
Q. Patients with endometriosis are often prescribed the birth control pill. Works?
R. It serves to reduce pain. The problem with the pill is that it contains estrogen, and the disease grows with estrogen, therefore, it is a very controversial situation, especially if one must do long-term therapy. Taking it for a few months is fine.
Q. And the surgery? When is it recommended?
R. Surgery has its uncertainties because interorgan foci do not emerge on the surface of the organs, and are not seen with surgery, and, therefore, are impossible to eliminate. In many cases, surgery, even if very radical, does not guarantee that all the disease will be eliminated. Also, you never know if it has fully developed when you did the surgery and it may be that some cells have not grown yet and will grow in one, two or five years, which requires more operations. It is not an effective therapy, because it has many limits.
Q. So what therapy works?
R. Right now, there is no definitive cure. Finding it is the dream of all gynecologists in the world. We are working, and we already have an Italian patent, to develop an immunological therapy. We are convinced that this will be the future of this disease. Create specific antibodies that wi
ll destroy or block cells, and possibly modify those found in the uterus. All our physical, intellectual and economic resources are in this.
Q. When can you expect it to be ready?
R. It's impossible to say for sure because research is like walking on rocks, it's extremely dangerous. It is a path full of obstacles. We are in the preclinical cellular phase, testing what we have produced in endometriosis cells and also in normal endometrium. After this phase, if everything goes well, we will have to do tests on animals and only then can it be passed on to humans. In the meantime, we must continue raising awareness. People, and doctors first, have to understand that it is a real disease, that it is not an invention. I have patients who come to us after their gynecologist has told them not to worry, that they need to be calm, or that it is stress. It is not like this.
Q. And in the meantime, what can be done to alleviate day-to-day ailments?
R. A thing that We developed more than 12 years ago and what works is the anti-inflammatory diet. The disease creates chronic inflammation, and estrogen is the gasoline that makes endometriosis grow. Furthermore, it has been proven that the more inflammation you have, the more the disease itself produces estrogen, which means it feeds itself. Our diet provides for a drastic reduction of inflammatory foods – such as red meat, dairy and gluten – and the implementation of foods that do the opposite: fruits, vegetables, legumes, fish rich in omega 3. By doing this, we achieve that The patient lowers her state of inflammation, and therefore, the production of estrogen, until the growth of the disease is slowed down.
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