Endometriosis: What’s the Latest Research?

Endometriosis is a chronic, gynecologic condition that affects around 190 million women and people assigned female at birth worldwide. The disease is caused by the growth of endometrial-like tissue, similar to the lining of the womb, in places outside of the uterus such as the ovaries, pelvic lining and fallopian tubes. Although some people with endometriosis do not experience any symptoms, the condition is characterized by severe pelvic pain that can increase during sex, painful and heavy menstruation, fatigue and issues with fertility.

Diagnosis of the disease involves an in-depth medical history review in combination with physical examinations, screening/imaging tests and, in some cases, laparoscopic surgery. There are currently no treatments available to cure the condition, but there are medications available to manage symptoms. Both non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics (painkillers) might be prescribed, as well as hormonal medications including the contraceptive pill. In certain individuals, surgery to remove the endometriosis tissue, or to remove part or all the affected organs, may also be advised.

Despite its high prevalence, endometriosis remains underdiagnosed, highlighting the need for increased awareness, research and improved treatment options.

Generating a cellular atlas of endometriosis

Last year, researchers from Cedars Sinai used single-cell genomics technology to map out the molecular profile of endometriosis, providing detail on the condition's complex cellular makeup. The analysis, published in Nature Gentetics, used nearly 400,000 cells from a total of 21 affected or healthy individuals to identify distinct molecular differences between various subtypes of the disease.¹

By identifying potential therapeutic targets at a cellular level, the study could enhance treatment outcomes and reduce disease recurrence. Moreover, the researchers draw parallels between endometriosis and cancer, highlighting the potential for utilizing similar genomic approaches to unravel the disease's mechanisms and develop targeted therapies.

“This resource can now be used by researchers all throughout the world to study specific cell types that they specialize in, which will hopefully lead to more efficient and effective diagnosis and treatment for endometriosis patients. It really is a game changer,” said Dr. Kate Lawrenson, an associate professor in the department of obstetrics and gynecology at Cedars-Sinai, and co-senior and corresponding author of the study.

Largest genetic study of endometriosis to date

Oxford University scientists – in collaboration with 24 international research teams – conducted the largest genetic study of endometriosis to date, published in Nature Genetics.² Using Data from the UK Biobank and 23andMe, they carried out a genome-wide association study of over 60,000 individuals diagnosed with endometriosis and more than 700,000 control subjects.

The study revealed 42 genetic regions that are significantly associated with the disease, many of which are related to pain perception. The researchers also identified genetic correlations with endometriosis and several pain conditions, suggesting potential shared mechanisms. Their findings offer promising avenues for developing targeted treatments and may potentially shift the focus from hormonal to pain-based therapies for endometriosis management.

Endometriosis and IBS share genetic risk factors

Researchers from the University of Queensland investigated the connection between endometriosis and gastrointestinal (GI) disorders in their study published in Cell Press.³ They analyzed data from 188,000 patients in the UK Biobank, which revealed those diagnosed with endometriosis had a significantly higher likelihood of being diagnosed with irritable bowel syndrome (IBS) and gastro-esophageal reflux disease. The study emphasizes a potential shared genetic predisposition between these conditions, and highlights the potential for repurposing existing drugs, such as pentoxifylline, to address common symptoms across both conditions. However, it also raises concerns regarding the use of NSAIDs in endometriosis management, given their potential to exacerbate GI complications.

The gut microbiome is altered in those with endometriosis

Given its association with GI disorders, researchers are investigating the potential role of the gut microbiome in endometriosis disease progression. Scientists from Baylor College of Medicine used a novel mouse model to demonstrate that alterations in the gut microbiome significantly influence the growth of endometriotic lesions in their study published in Cell Death & Discovery.⁴

Germ-free mice exhibited smaller lesions than the control group, while those receiving fecal microbiome transfers from mice with endometriosis experienced increased lesion growth. The researchers also identified specific microbiome-derived metabolites, such as quinic acid, that promoted cellular proliferation and lesion growth.

The study proposes the use of microbiome metabolites as diagnostic markers, offering a non-invasive approach to identify and monitor endometriosis.

“We are investigating whether microbiome metabolites in human stool samples could be a useful diagnostic tool and also whether some of these metabolites could be used as a treatment strategy,” said lead author Dr. Rama Kommagani, associate professor in the departments of pathology and immunology and of molecular virology and microbiology at Baylor.

Endometriosis associated with increased risk of psychiatric conditions

As well as GI conditions, endometriosis is also associated with several other co-morbidities, including psychiatric disorders. A study from Yale Medicine investigated the interplay between endometriosis and psychiatric conditions such as depression, anxiety and eating disorders in a study published in JAMA Network Open.⁵ While past research suggested these mental health issues were merely byproducts of chronic pain, the study reveals their distinct genetic underpinnings, expanding our understanding of endometriosis beyond its reproductive implications.

The study used data from the UK Biobank featuring over 8,200 endometriosis patients and 194,000 healthy controls. The researchers found a heightened prevalence of psychiatric conditions among those with endometriosis and discovered shared genetic variants linking endometriosis with depression.

“For a long time, researchers thought it was just a gynecological disease ... but we have to acknowledge that the effects of endometriosis extend far beyond reproduction,” said first author Dr. Dora Koller, a postdoctoral fellow at the University of Barcelona and Yale University School of Medicine.

Advancing our understanding of endometriosis

Endometriosis represents a multifaceted challenge affecting millions of individuals globally. Recent studies have massively advanced our understanding of how the condition affects individuals and is helping to improve the lives of those affected by this debilitating disease. Several active associations, such as Endometriosis UK and the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, are helping fund the next generation of endometriosis research.

References:

1. Fonseca MAS, Haro M, Wright KN, et al. Single-cell transcriptomic analysis of endometriosis. Nat Genet. 2023;55(2):255-267. doi: 10.1038/s41588-022-01254-1

2. Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423-436. doi: 10.1038/s41588-023-01323-z

3. Yang F, Wu Y, Hockey R, et al. Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management. Cell Rep Med. 2023;4(11):101250. doi: 10.1016/j.xcrm.2023.101250

4. Chadchan SB, Naik SK, Popli P, et al. Gut microbiota and microbiota-derived metabolites promotes endometriosis. Cell Death Discovery. 2023;9(1):28. doi: 10.1038/s41420-023-01309-0

5. Koller D, Pathak GA, Wendt FR, et al. Epidemiologic and genetic associations of endometriosis with depression, anxiety, and eating disorders. JAMA Netw Open. 2023;6(1):e2251214. doi: 10.1001/jamanetworkopen.2022.51214