Endometriosis affects multiple body systems beyond pelvic pain

Migraines, digestive problems, anxiety, and depression can be part of endometriosis, although they are often interpreted as separate conditions. Research led by the Sant Pau Research Institute (IR Sant Pau) and published in Human Reproduction has identified different symptom patterns in more than 22,000 women, reinforcing the idea that the disease extends far beyond its traditional gynecological manifestations.

For years, endometriosis has been classified primarily according to the location and extent of lesions observed through surgery or imaging tests. However, these systems only partially describe patients' real-life experiences and do not adequately explain the enormous variability in symptoms associated with the disease. In addition, a definitive diagnosis cannot rely solely on invasive surgical procedures that involve risks, costs, and a lengthy recovery period.

To better understand this heterogeneity, researchers from the United States and Spain analyzed clinical and health data from women with endometriosis enrolled in the All of Us Research Program, one of the world's largest population-based biobanks. The study identified different symptom patterns and examined how they relate to quality of life and disease severity.

Dr. Dora Koller, researcher with the Women's Health and Perinatal Research Group at IR Sant Pau and senior author of the studyFor a long time, endometriosis was considered primarily a gynecological disease, but growing evidence indicates that it affects multiple systems throughout the body. Understanding this diversity is essential to improve recognition of the disease and move toward more personalized care."

Endometriosis impacts approximately 10% of women of reproductive age, and diagnosis is often delayed by four to eleven years after the onset of the first symptoms. This is partly because its manifestations can vary greatly from one woman to another and are frequently minimized, attributed to nonspecific causes, or not recognized in time.

Beyond pelvic pain

To conduct the study, the researchers analyzed 19 symptoms and comorbidities frequently associated with endometriosis, including chronic pelvic pain, abdominal pain, gastrointestinal symptoms, migraine, anxiety, depression, chronic fatigue, infertility, and irritable bowel syndrome.

The analysis identified four major symptom patterns among premenopausal women, who were considered the group most representative of active disease. The first profile, which included 18.8% of patients, was characterized by a high disease burden, with severe pain, gastrointestinal symptoms, and mood disturbances. A second group, the largest, represented 30% of women and had moderate symptoms, mainly related to pain and emotional health.

The third profile, found in 29.6% of patients, was dominated by psychological and neurological symptoms such as anxiety, depression, and migraine. Finally, 20.6% of women were included in a group with a much lower symptom burden.

This distribution differed from that observed in the study's overall cohort, in which the group with the lowest clinical burden was considerably larger. This difference reinforces the idea that endometriosis during the reproductive years is rarely a silent disease and that most patients fall into profiles with clearly defined symptoms.

"The identification of this psychological and neurological profile shows us that endometriosis does not always present in the way we expect, and that these symptoms may be recorded for the first time even in women seeking care for physical complaints. If we continue to think only in terms of pelvic pain or menstrual pain, we risk overlooking many patients," says Dr. Koller.

A possible explanation for diagnostic delays

Identifying these patterns also helps explain why many women wait years to receive a diagnosis. When digestive, neurological, or psychological symptoms predominate, their connection to endometriosis may go unnoticed, leading to repeated consultations across different specialties before a common explanation is found.

A patient may initially seek care for recurrent migraines, digestive discomfort, anxiety, fatigue, or chronic pain without these symptoms being interpreted as part of the same underlying process. As a result, patients often move through multiple care pathways before receiving a definitive diagnosis.

"Many patients spend years searching for an explanation for symptoms that are assessed separately. Recognizing that endometriosis can present in very different ways could help identify it earlier and reduce years of uncertainty for many women," says Dr. Koller.

The researcher notes that one of the study's key messages is the need to adopt a more integrated view of the disease. "If a woman has menstrual pain but also migraines, digestive symptoms, or mental health problems, it is important to consider whether all these manifestations may be related. Too often, they are assessed separately when they may be part of the same clinical picture," she explains.

Greater awareness of this clinical diversity could promote earlier recognition of the disease, particularly in primary care, where initial consultations frequently take place. It could also facilitate faster referrals to the appropriate specialists and reduce the time between symptom onset and the start of treatment.

Adenomyosis is associated with the most severe forms

The study also examined women with coexisting endometriosis and adenomyosis. Adenomyosis is a condition closely related to endometriosis in which tissue similar to the endometrium grows within the muscular wall of the uterus, causing severe pain, heavy menstrual bleeding, and other gynecological symptoms.

The results indicated that these patients had significantly more severe clinical profiles than women with endometriosis without adenomyosis. In the cohort analyzed, 57% were concentrated in the groups with the highest symptom burden, characterized by severe pain, gastrointestinal symptoms, and emotional distress.

In addition, the low-symptom-burden profile identified in other patients was virtually absent from this subgroup. The coexistence of both conditions was consistently associated with particularly complex and debilitating forms of the disease.

"Adenomyosis appears to act as a factor that substantially increases the clinical burden of endometriosis. When both diseases coexist, we observe a greater concentration of patients in the most severe profiles," explains Dr. Koller.

These findings reinforce the importance of identifying the simultaneous presence of both conditions and suggest that patients with endometriosis and adenomyosis may benefit from more individualized monitoring and management strategies.

Impact on quality of life

In addition to identifying different symptom patterns, the study assessed how these profiles relate to patients' quality of life. The results revealed clear differences among the groups, proposing that the identified profiles reflect not only different ways in which the disease presents but also different levels of impact on daily life.

Women in the groups with the highest symptom burden had poorer physical and mental health, greater limitations in carrying out daily activities, and more difficulties in areas such as social relationships and emotional well-being. They also reported a poorer perception of their overall health and lower satisfaction with their quality of life.

The differences were not limited to pain or physical symptoms. The most severe profiles had poorer outcomes across nearly every dimension assessed, from functional ability to mental health. In contrast, women in the groups with a lower clinical burden experienced much more limited effects.

The analysis also revealed differences in less obvious aspects of daily life. Patients with more severe profiles showed lower participation in certain social activities and were more likely to experience limitations in mobility or personal independence. These findings demonstrate that the impact of endometriosis extends far beyond the gynecological sphere and can affect multiple aspects of everyday life.

"We often tend to assess the disease based on the intensity of pain or the extent of the lesions, but our results show that its real impact is much broader. Endometriosis can impact physical health, mental health, social relationships, and quality of life in very different ways depending on each patient's profile," says Dr. Koller.

"For years, we have tried to classify endometriosis primarily according to the location of the lesions. Our results show that understanding how the disease presents in each patient may be equally important for improving diagnosis and clinical care," she concludes.

Source:

Institut de Recerca Sant Pau (Sant Pau Research Institute)

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