Biomarkers of endometriosis

Abstract

An endometriosis biomarker can reduce diagnostic delay, permit studying disease prevlence and may be used to monitor response to treatment. Despite extensive research, a validated endometriosis biomarker does not exist. In the current thesis, we ask several questions. First, we ask if diagnostic accuracy studies on blood biomarkers of endometriosis are adequately reported? We assume that inadequate reporting of research on blood biomarkers of endometriosis can be one of the reasons why a clinically useful biomarker of endometriosis could not be identified. Second, since diagnostic delay is one of the consequences of the absence of an endometriosis biomarker, we try to find out if Egyptian women with endometriosis suffer such a diagnostic delay? We also investigate if endometriosis is affecting their quality of life? Third, we ask if the mechanical properties of eutopic endometrial stromal cells of endometriosis patients differ from those of control women? And if such a difference can form the basis for a mechanical biomarker of endometriosis? Fourth, we enquire if estrogen is metabolized in women with endometriosis in a different way than it is metabolized in women without the disease? We assume that in endometriosis, estrogen is metabolized along more estrogenically active pathways. Fifth, we investigate the evidence of efficacy and safety of a new class of hormonal medications, oral gonadotropin releasing hormone antagonist (oral GnRH antagonists) in combination with estradiol and progestin for the treatment of endometriosis-related pelvic pain. Throughout the work in this thesis, we reached the following answers to the above-mentioned questions: Chapter 2: Our results showed that studies on blood biomarkers of endometriosis are incompletely reported. Adherence to STARD 2015 improves slightly with advancing publication year, with studies published after 2015 having higher STARD 2015 adherence than those published before 2015. Studies published in higher impact factors journals have higher adherence to STARD 2015 than those published in lower impact factor journals. Authors, reviewers and journal editors should focus, particularly, on items that are poorly reported to include them in research protocols, actual study implementation and study reporting. Chapter 3: Egyptian women with endometriosis experience a relatively short diagnostic delay (36 months), and poor bodily pain scores. In addition, Egyptian endometriosis patients have impaired physical health scores. Determining factors of the poor quality of life affecting Egyptian women with endometriosis are patient’s age, disease stage and non-cyclical pelvic pain. Chapter 4: We characterize the mechanical phenotype of eutopic endometrial stromal cells of endometriosis patients using a high throughput microfluidics platform implying velocity of cells inside microchannel constriction as surrogate for cellular stiffness. We found that eutopic endometrial stromal cells of endometriosis patients have increased deformation index and cross microchannel system faster than their counterparts of control women. These biomechanical features of eutopic endometrial stromal cells of endometriosis can lay the foundation for identifying a mechanical biomarker of the disease. Chapter 5: Compered to its counterpart of control women, eutopic endometrium of women with endometriosis metabolizes estrogen preferentially towards the biologically active 2-hydroxyesterone (2OHE2), and the potentially genotoxic 4-hysdroxyesterone (4OHE1) and 4-hydroxyestradiol (4OHE2) metabolites. This provides explanation on endometriosis etiology, link between endometriosis and cancer, and may help identifying endometrial biomarkers of the disease. Chapter 6: Oral GnRH antagonists including elagolix, relugolix alone or with ad-back hormonal theraoy therapy, and linzagolix represent a promising addition in the armamentarium against endometriosis related pain. However, several questions need to be investigated and answered further before they can be correctly positioned in the algorithm of treatment of endometriosis associated pelvic pain.