The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario.

There is strong evidence from humans and animal models showing that abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and/or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems, contributing to disease. Stress is known to affect the physiology of pelvic organs and to disturb the HPA axis leading to chronic, painful, inflammatory disorders. A link between stress and disease has already been documented for many chronic conditions. Endometriosis is a complex chronic gynecological disease associated with severe pelvic pain and infertility that affects 10% of reproductive-aged women. Patients report the negative impact of endometriosis symptoms on quality of life, work/study productivity, and personal relationships, which in turn cause high levels of psychological and emotional distress. The relationship between stress and endometriosis is not clear. Still, we have recently demonstrated that stress increases the size and severity of the lesions as well as inflammatory parameters in an animal model. Furthermore, the "controllability" of stress influences the pathophysiology in this model, offering the possibility of using stress management techniques in patients. The crosstalk between stress-inflammation-pain through HPA axis activity indicates that stress relief should alleviate inflammation and, in turn, decrease painful responses. This opens up the opportunity of altering brain-body-brain pathways as potential new therapeutic option for endometriosis. The goal of this review is to gather the research evidence regarding the interaction between stress (psychological and physiological) and the development and progression of endometriosis on the exacerbation of its symptoms with the purpose of proposing new lines of emerging research and possible treatment modalities for this still incurable disease.