Metabolomics in endometriosis: challenges and perspectives for future studies

Endometriosis is a complex disease characterized by inflammation and the growth of endometrial- like glands and stroma outside the uterine cavity. The pathophysiology of endometriosis is not entirely understood, however, with a prevalence of ~10% of women in their reproductive years, the disease symptoms significantly affect the quality of life of millions of women globally. Metabolomic studies have previously identified specific metabolites that could be a signature of endometriosis. This approach could potentially be used as a non-invasive tool for early diagnosis and provide a better understanding of endometriosis pathophysiology. This review aims to provide insight as to how endometriosis affects the metabolome by reviewing different studies that have used this approach to design follow-up studies. The search query included the term 'endometriosis' in combination with 'metabolomics', 'lipidomics', or 'sphingolipidomics' published between 2012 and 2020. We included studies in humans and animal models. Most studies reported differences in the metabolome of subjects with endometriosis in comparison to healthy controls and used samples taken from serum, endometrial tissue, follicular fluid, urine, peritoneal fluid, or endometrial fluid. Statistically significant metabolites contributed to group separation between patients and healthy controls. Reported metabolites included amino acids, lipids, organic acids, and other organic compounds. Differences in methods, analytical techniques, and the presence of confounding factors can interfere with results and interpretation of data. Metabolomics seems to be a promising tool for identifying significant metabolites in patients with endometriosis. Nonetheless, more investigation is needed in order to understand the significance of the study results. LAY SUMMARY: Endometriosis is a chronic disease affecting the quality of life in one out of every ten women during their reproductive years, causing pain and infertility. It is characterized by inflammation and growth of tissue like the endometrium (uterus lining) outside the uterine cavity. Studies have searched for a predictor of endometriosis-associated changes by observing small molecules necessary for metabolism on a large scale (metabolomics). Metabolomics could serve to resolve one of the biggest challenges that patients with endometriosis face: a delay in diagnosis. In this review, the authors summarize identified potential biomarkers from various bodily fluids and tissues that are characteristic of metabolic processes observed in endometriosis. Biomarkers include cell growth, cell survival, high energy demand, oxidative stress, and fatty acid levels. A metabolomics approach offers promise as a non-invasive tool to identify significant metabolite changes in patients with endometriosis, potentially leading to earlier diagnoses and new opportunities for back-translational strategies.