Metformin as a Potential Treatment Option for Endometriosis

SIMPLE SUMMARY: The aim of this article is to present current knowledge regarding the possibilities of using metformin in the pharmacological treatment of endometriosis. Metformin is an insulin sensitizer widely used for the treatment of type 2 diabetes mellitus. 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 regresses endometriotic implants by increasing the activity of superoxide dismutase. It is also an inhibitor of metalloproteinase-2, decreasing the levels of the vascular endothelial growth factor and matrix metalloproteinase-9 in animal studies. 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. It could be a missing link for the successful treatment of this chronic disease. ABSTRACT: 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. These pathophysiological disturbances interact with one another through mechanisms that are still awaiting elucidation. The aim of this article is to present current knowledge regarding the possibilities of using metformin in the pharmacological treatment of endometriosis. Metformin is an insulin sensitizer widely used for the treatment of type 2 diabetes mellitus. 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 regresses endometriotic implants by increasing the activity of superoxide dismutase. It is also an inhibitor of metalloproteinase-2, decreasing the levels of the vascular endothelial growth factor and matrix metalloproteinase-9 in animal studies. In endometriosis, metformin might modify the stroma–epithelium communication via Wnt2/β-catenin. 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. It could be a missing link for the successful treatment of this chronic disease.