From 40 to 500 rules on average throughout life: how social changes have increased the risk of endometriosis in women

Almost a decade. That is the temporal abyss that, on average, a woman in Catalonia has to go through before discovering that the pain she suffers is not "what is to be expected", but a disease that has a name: endometriosis. Currently, one in ten Catalan women lives with this chronic and inflammatory pathology that hijacks their physical and emotional health due to the historical normalization of female pain. For Dr. Francisco Carmona, head of gynecology at the Hospital Clínic and an international reference in the field, the label "silent disease" is a trap. In reality, it has been a pathology silenced by gender bias in scientific research. His statement could not be more graphic: "If men had testicular pain five days a month, the world would have stopped years ago."

Today, however, the paradigm is changing: artificial intelligence and new diagnostic engineering have taken over to offer, finally, personalized answers and treatments to a generation of patients who have said enough. "I've lost count of the times I've been told that the pain I felt was normal or that some women were more sensitive than others," recalls Lorena Martínez Pérez, 44, president of the Association of Women Affected by Endometriosis of Catalonia (Endo&Cat). For her, the root problem is invisibility: "We have lived for years without anyone truly believing us."

An unexpected colonization

Endometriosis behaves like a kind of relentless expansion. Cells that should live confined within the uterus –forming the endometrium, the membrane that hosts the embryo– decide to travel and settle in unusual places: in the ovaries, in the intestines, in the bladder, or even in the lungs or the sciatic nerve. The molecular drama begins with each menstrual cycle. These rebellious tissues respond to hormones just like the uterus: they grow, inflame, and bleed. But, unlike what happens during menstruation, this blood has no way out to the exterior. This unleashes a chemical storm in which the body, in a desperate attempt to defend itself from this invasion, releases an inflammatory combination loaded with three key elements: interleukins, messenger molecules that sound the chemical alarm to call for defenses; macrophages, cells that should act as a cleaning crew to eliminate excess tissue, but which here often end up fueling the chaos; and prostaglandins, the molecules that cause contractions and are the true culprits of sharp pain. This uncontrolled army does not stay put in the pelvis, but travels through the bloodstream and intoxicates the rest of the body, causing it to cease being a local problem and become a systemic disease that changes the body's entire chemistry.

–chemical substances present in plastics or cosmetics that This «trigger» is epigenetics, the field of science that studies how the environment can turn our genes on or off. Factors such as nutrition, exercise, or exposure to endocrine disruptors –chemical substances present in plastics or cosmetics that trick our hormones– can be the ones that trigger the disease. Furthermore, a cleaning error in the immune system comes into play. In most women, when part of the menstrual tissue flows back into the body instead of out (retrograde menstruation), the defenses naturally eliminate it. In contrast, in patients with endometriosis, the cleaning system fails: the body is unable to digest these foreign cells and allows them to take root and proliferate, becoming a chronic threat.

DUFIC, a device for the collection of 'in vivo' uterine fluidsFrom anatomy to biochemistry

Until now, to name endometriosis, one had to go through surgery, almost inevitably. This reliance on invasive methods, such as laparoscopy or suction endometrial biopsies, has fueled diagnostic delays for decades and left patients in an often exhausting surgical waiting list just to obtain official confirmation. The new scientific paradigm, however, aims to retire the scalpel in favor of molecular precision: moving from anatomy –looking at tissue shape– to biochemistry –deciphering proteins.

One of the most innovative projects in this line is DUFIC, a device for 'in vivo' uterine fluid collection, led by researcher Analuce Canha Gouveia and Dr. Sánchez-Ferrer. This device, selected by the CaixaImpulse Innovation program of the La Caixa Foundation, uses capillarity –a physical phenomenon similar to a sugar cube absorbing coffee– to collect uterine fluid passively. Unlike traditional biopsy, the method is practically painless and allows inflammatory markers to be identified long before lesions are visible on an ultrasound.

Beyond uterine fluid, science is exploring other non-invasive avenues to streamline screening. In countries like France, Germany, or Switzerland, saliva tests based on micro-RNA profiles are already used, a liquid biopsy that detects the genetic trace of the pathology with a minimal sample. In parallel, the analysis of menstrual blood and the search for markers in blood are advances that have already reached leading scientific journals such as Nature Communications.

Personalized treatment

The final frontier of research seeks not only to detect the disease, but also to decipher it. Until now, endometriosis has been treated as a uniform block, but science has begun to understand that, in reality, it is a puzzle of different biological entities. Research wants to repeat the success of oncology: if breast cancer ceased to be a single disease to divide into molecular subtypes, endometriosis is now seeking its own barcode. This classification, which three decades ago changed the course of the fight against cancer, is what today allows saving thousands of lives thanks to precision medicine.

Using theatlas of human endometrial cells –an exhaustive genetic map–, researchers are identifying subtypes of the disease according to their molecular profile. "It should not only tell us 'you have endometriosis', but also what type it is: if it will progress rapidly or if it can cause infertility," says Dr. Carmona. Identifying these subtypes would also allow predicting the aggressiveness of the pathology from the moment of diagnosis. Having this molecular prognosis would give women the key to plan their lives and their motherhood with real data and would free them from the chronic uncertainty that has marked their medical lives until now.

This advance in precision medicine aims to put an end to the tedious method of trial and errorThis advance in precision medicine aims to end the tedious method of