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Endometriosis and intestinal disorders: a missing genetic link?

In clinical practice, endometriosis and gastrointestinal disorders such as irritable bowel syndrome commonly coexist. Recent studies have confirmed that women with endometriosis have a higher risk of IBS than women without.

Now a preprint article published on medRxiv potentially figured out why. This Australian study, which has not yet been peer reviewed, found a genetic link between endometriosis and digestive disorders.

“Shared genetic loci may contribute to risk of endometriosis and digestive disorders due to involvement of DNA damage, estrogen-regulated cell proliferation and inflammation, and barrier dysfunction,” wrote the authors.

One author, Dr Sally Mortlock from the Institute for Molecular Bioscience at the University of Queensland, said Preview+ that they used large-scale, multi-faceted data, including observational, genetic, and pharmaceutical datasets.

“We had information on millions of variants, or genetic variants across the genome, those that were associated with endometriosis and those that were associated with gastrointestinal disorders. So we were able to use a range of statistical approaches to compare these risk variants to see which were common across diseases,” she explained.

Researchers have found a relationship between endometriosis and a variety of gastrointestinal diseases.

Their analyzes “supported a causal relationship between genetic predisposition to gastrointestinal disorders (gastroesophageal reflux [GORD] and peptic ulcers [PUD]) and the risk of endometriosis, and evidence for a bidirectional causal relationship between endometriosis and IBS, which may partly explain the co-occurrence of these diseases,” the authors wrote.

What are the implications of this shared genetics?

The implications of such a finding are significant, say the authors.

Endometriosis is a common gynecological disorder that affects up to 11% of women. Although recognition of the disease is improving, it can take an average of 7 years from the onset of symptoms to diagnosis.

Part of the reason for the long diagnosis is that the symptoms are so similar to other conditions, including gastrointestinal disorders. It has been observed that many women with endometriosis experience symptoms such as abdominal pain, bloating, constipation, heartburn, dyspepsia, vomiting, painful stools, diarrhea and nausea. Although these symptoms do not necessarily imply bowel damage associated with endometriosis, some symptoms such as cycle-related bloating, constipation, and diarrhea may worsen during menstruation.

Another study author, Professor Jenny Doust of the University of Queensland School of Public Health, said she hoped the study would highlight the possibility of joint diagnoses when studying the endometriosis and gastrointestinal disorders.

“Clinicians need to be aware that there is this crossover between symptoms. Thus, people with endometriosis quite often have gastrointestinal symptoms. And people with wombs, who have gastrointestinal symptoms can have endometriosis,” she said.

The pharmacological response

One of the reasons it is so important to recognize these two diagnoses is how common medications can affect the symptoms of both diseases.

“Women with endometriosis use higher levels of nonsteroidal anti-inflammatory drugs, which you would expect, but they also use higher levels of proton pump inhibitors and laxatives. [if they have gastrointestinal problems]said Professor Doust.

“In particular, since a laxative is something you can get over-the-counter, clinicians may not even be aware this is happening,” Professor Doust said.

The document emphasized that caution should be exercised regarding the contraindications of certain medications.

“Painkillers or anti-inflammatories taken for endometriosis might actually inflame some sort of gastrointestinal disorder – they can inflame peptic ulcer, for example,” Dr. Mortlock explained.

The future of endometriosis

Endometriosis has been severely understudied, but hopefully the tide is turning. The federal government launched an Endometriosis Action Plan in 2018, with the goal of improving endometriosis research programs and increasing treatment options.

This MedRxiv article examines whether some common treatments for IBS could also help people with endometriosis.

“Further evidence of drug repositioning potential includes that visceral tenderness and chronic low-grade inflammatory status have been key features of both IBS and endometriosis and that therapies aimed at alleviating pain in IBS may also relieve pain during menstruation,” the authors wrote.

The low-FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) diet is a common therapeutic dietary protocol for IBS, but there is a growing body of research into whether it might also benefit sufferers. of endometriosis. A New Zealand study found that women with concurrent IBS and endometriosis had a significantly higher response rate to the low-FODMAP diet than patients with IBS without known endometriosis.

These are integrated approaches and broader thinking that may be more common in the future of endometriosis treatment.

“Having this kind of integrated approach seems like an ideal thing because often people with endometriosis are not treated adequately. And there is plenty of evidence that women with endometriosis have persistent problems with pain,” Professor Doust suggested.

Although still in its infancy, it is also hoped that this genetic discovery may help in diagnosis in the future.

“Our long-term goal is definitely to create more diagnostic aids in the field (in particular) of endometriosis. It is a long process that will not happen immediately. But the idea would be to bring this knowledge of the relationship to other diseases to facilitate earlier diagnosis,” concluded Dr Mortlock.

Caitlin Wright is a Sydney-based freelance journalist and Editor of the Year 2022 who writes for communities and organizations that care.

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