A defective immune response has a triggering effect on both cellular and humoral responses. The adhesion of endometrial fragments to the peritoneum is enhanced by upregulated biomolecules such as selectins, integrins, and cadherins, whereas the process of the further implantation and remodelling of the cellular matrix is controlled by MMP-1, 2, 9, and 11. Metalloproteinases (MMPs), prostaglandins (PGs), and chemokines may also be released. Some studies demonstrate fundamental changes in the concentration of interleukins (ILs i.e., IL-10, IL-6, IL-8), growth factors, or adhesion molecules in the peritoneal fluid and peripheral blood obtained from patients suffering from endometriosis. Reaching the pelvis via transtubal retrograde flow, the overreactive uterine endometrium may cause adhesion, implantation, and proliferation of the ectopic tissue into the peritoneal cells. One of the latest widely presented theories postulates that endometriosis arises from an abnormal response to inflammatory processes. According to, numerous interactions at the hormonal, genetic, immunological, and environmental levels are responsible for the development of this type of pathology. Although many mechanisms leading to the development of this condition are still awaiting elucidation, several hypotheses on the pathogenesis of endometriosis, both local and systemic, have been emphasized. It could be a missing link for the successful treatment of this chronic disease.Įndometriosis is a multidimensional, chronic and incurable disease of unclear aetiology.
With its unique therapeutic mechanisms and no serious side effects, metformin seems to be a helpful anti-inflammatory and anti-proliferative agent in the treatment of endometriosis. In endometriosis, metformin might modify the stroma–epithelium communication via Wnt2/β-catenin. It is also an inhibitor of metalloproteinase-2, decreasing the levels of the vascular endothelial growth factor and matrix metalloproteinase-9 in animal studies. Metformin regresses endometriotic implants by increasing the activity of superoxide dismutase. The pleiotropic effects of metformin are mainly exerted through the activation of AMP-activated protein kinase, which is the key cellular energy homeostasis regulator that inhibits mTOR, a major autophagy suppressor. Metformin is an insulin sensitizer widely used for the treatment of type 2 diabetes mellitus. The aim of this article is to present current knowledge regarding the possibilities of using metformin in the pharmacological treatment of endometriosis. These pathophysiological disturbances interact with one another through mechanisms that are still awaiting elucidation. Endometriosis is a common disease in women of reproductive age, and its pathogenesis seems to be largely affected by hormone imbalance, inflammation, oxidative stress, and autophagy dysregulation.
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