Research published in the journal Human Reproduction reveals that women with endometriosis are at a significantly higher risk for developing a range of autoimmune, autoinflammatory, and mixed-pattern diseases.
The new study, of unprecedented scale, examines not only clinical associations, but also for the first time the biological basis for these comorbidities - through genetics. It identifies osteoarthritis, rheumatoid arthritis, multiple sclerosis, coeliac disease, and psoriasis among the comorbid conditions significantly linked to endometriosis.
These insights not only enhance our understanding of the relationship between endometriosis and immune conditions but also pave the way for better-targeted treatments, the potential for repurposing of existing treatments between conditions, and early interventions.
Key Findings:
• Women with endometriosis were found to have a 30-80% increased risk of developing autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and coeliac disease, as well as autoinflammatory conditions like osteoarthritis and psoriasis.
• The study uncovered a genetic correlation between endometriosis and several of these diseases, suggesting that a shared genetic basis may underlie the increased risk. Specifically, genetic analysis showed correlations between endometriosis and both osteoarthritis and rheumatoid arthritis, and to a more limited extent multiple sclerosis.
• Analysis indicated a potential causal link between endometriosis and rheumatoid arthritis, highlighting that the presence of one condition may contribute to the development of the other.
The study used data from the UK Biobank, one of the largest databases available, to conduct a comprehensive analysis of over 8,000 endometriosis cases and 64,000 immunological disease cases. The researchers examined the association between endometriosis and 31 different immune conditions categorised as classical autoimmune diseases, autoinflammatory diseases, and mixed-pattern diseases.
The team performed genome-wide association studies (GWAS) and meta-analyses to explore genetic correlations between endometriosis and these immune conditions. The study also employed Mendelian randomisation to investigate potential causal relationships, identifying specific genetic variants shared between endometriosis and autoimmune diseases. This analysis helped pinpoint key genetic variants that may contribute to both conditions. The research was mainly funded by Wellbeing of Women UK.
What this means for women's health
This research is important in understanding the shared biological mechanisms between endometriosis and immune-related diseases. This understanding opens up exciting possibilities for new therapeutic approaches, including drug repurposing or the development of combined treatments for endometriosis and related immunological conditions. The findings also suggest that women with endometriosis should be more closely monitored for the development of immunological conditions, as early detection could significantly improve patient outcomes.
Dr. Nilufer Rahmioglu, joint senior author from the Nuffield Department of Women's & Reproductive Health at the University of Oxford, emphasised: 'Sex differences are well documented across various immune conditions, many of which are more prevalent in females. This is also the case for many auto-immune and inflammatory diseases. These conditions have been reported more frequently by women with endometriosis, but we don't know why. Female-specific genetic studies such as we conducted here can help to find out and uncover the biology behind these disease processes.'
Professor Krina Zondervan, joint senior author and Head of the Nuffield Department of Women's & Reproductive Health at the University of Oxford, said: 'Very large studies integrating clinical and genetic information, such as conducted here, are able to provide valuable new insights into disease biology. In this case, we have provided solid evidence of a link between endometriosis and subsequent risk of diseases such as osteoarthritis and rheumatoid arthritis, and we have shown this has a biological basis. This new information can now be leveraged to look for new treatment avenues that may work across these conditions.'
Janet Lindsay, CEO of Wellbeing of Women added: 'This research is an important step towards building a more accurate understanding of endometriosis, a condition that affects 1/10 women globally. The findings show a link between endometriosis and autoimmune diseases that could pave the way towards faster diagnosis and more personalised treatments.
'For too long there has been too little investment in research into women's health issues like endometriosis. It is crucial that we increase research investment in the next generation of women's health researchers to expand our knowledge and improve patient outcomes.'
The research team hopes to explore potential therapeutic strategies that could simultaneously address endometriosis and its associated immune conditions. Further studies focusing on biomarker identification, clinical trials, and targeted treatment options will be essential in moving from understanding the genetic and phenotypic associations to actionable healthcare solutions.
The full paper, ' The phenotypic and genetic association between endometriosis and immunological diseases ', can be read in Human Reproduction
About Nuffield Department of Women's and Reproductive Health, University of Oxford
About Wellbeing of Women
https://www.wellbeingofwomen.org.uk
