Endometriosis is one of the most frequent benign gynecological diseases and it is defined by the histological presence of endometrial glands and stroma outside the uterine cavity.The multifactorial etiopathogenesis of endometriosis appears to be very complex and poorly understood, involving a variety of environmental, immune and genetic factors. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease (Caserta et al., 2014). The principal symptom is chronic pelvic pain, which can take on different forms according to the location and seriousness of the pathology, and can manifest as dyspareunia, dyschezia, dysmenorrhea, lower urinary tract syndrome. It is also a major cause of infertility, which in turn causes psychological stress, low self-esteem and depression. These symptoms have a negative effect on the woman's overall quality of life (Caserta et al., 2015).
Objective of this study would be to evaluate the levels of various proinflammatory cytokines in the serum and peritoneal fluid of women with and without endometriosis, and to correlate these levels with the disease stage and pain symptoms, and to analyze the disease by a bio-psycho-social approach.
This project serves as proof of principle to investigate the role of chronic inflammation, through the expression of pro inflammatory cytokines and to correlate it with the disease related symptoms and severity.
By evaluation of these aspects we want to evaluate in women with endometriosis how symptoms can affect quality of life, sexual functioning, body image, anxiety and depression scores Women with dyspareunia have been found to be more anxious than women experiencing no pain (e.gKhander et al 2011) and the association of dyspareunia with depression symptoms has also been investigated considering longitudinal studies and large population samples (Chen et al., 2017).However the results has been inconsistent and concerns can be raised concerning methodological problems. In fact, a correct diagnosis of endometriosis according to the international guidelines, the use of validated questionnaires to evaluate the presence of mood disorders and exclusion of other comorbidities are lacking (Laganà et al., 2017). Finally the majority of the studies conducted are of correlations nature and it¿s difficult to establish causality between presence or severity of endoemtriosis, dyspareunia and sympotms of depression and anxiety. Moreover cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF), adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), and glycodelin A play important parts in the regulation of the proliferation, activation, motility, chemotaxis, adhesion, morphogenesis and implantation of various cells, including endometrial cells(5).Furthermore abnormal expression of glycodelin A has been associated with endometriosis(6).Women with endometriosis have high levels of IL-6, leading to increased haptoglobin production in the endometrium; ICAM-1 is also suggested to play a part in chemotaxis, motility, and adhesion of cells, so sharing in the pathogenesis of endometriosis (3).ST2 is a member of the IL-1 receptor family, which transduces the effects of interleukin-33.In normal conditions, the serum concentration of soluble ST2 is below the detectable level, but elevated concentration has been reported in patients with autoimmune diseases(7). Gal-3 is involved in many biological processes(8) and is dependent on the menstrual cycle, suggesting a role in the regulation of the endometrial function. Several studies showed that peritoneal IL-33 and Gal-3 concentration are strikingly elevated in endometriosis, especially in patients with deeply infiltrating disease ant there is an important correlation between the stage of endometriosis and peritoneal levels of Gal-3 and ST2 (1).
These factors are thought to contribute to the pathogenesis of endometriosis and correlate with chronic pelvic inflammation, which is the main pathogenetic substrate of pain symptoms.Endometriosis has also been negatively correlated to body image and femininity (Riazi et al., 2014; Fritzer et al., 2013; Leis et al., 2014). However very few studies investigated this issue and none of them did it on a longitudinal design or evaluating differences in body satisfaction before and after the surgical treatment.
Moreover, to our knowledge, the role that optimism can play in managing the symptoms of endometriosis has never been considered before. Regarding this point, this project is innovative for several reasons:
- it evaluates and compares levels of various proinflammatory cytokines in the serum peritoneal fluid of women with and without endometriosis;
- it correlates citokines expression in peritoneal fluid with stage and severity of the disease and these biomarkers can be use for diagnosis and treatment of endometriosis;
- it evaluates in a sample of women with endometriosis how symptoms of endometriosis can affect quality of life, sexual functioning, body image, anxiety and depression scores;
- it evaluates the correlation between the levels of citokynes and quality of life, sexual functioning, body image, anxiety and depression scores;
- it uses implicit measures of optimism which, compared to self-reports cannot be biased by participants ability to describe themselves;
- it uses two separate measures of optimism related to two important aspects of this condition.
We expect to find that women with endometriosis and dyspareunia will report less symptoms of anxiety and depression after the surgical intervention. We hypothesize that they have more symptoms when compared to women with edometriosis but without dyspareunia in the pre-surgery condition. We expect that symptoms of depression and anxiety are positively correlated to levels of citokines, severity of endometriosis, and self-rate intensity of pain, quality of life, sexual function and sexual satisfaction which could increase after the surgical interventions.