Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis

Endometriosis, one of the most common benign gynecological diseases, affects millions of women of childbearing age. Endometriosis-associated pain is a major cause of disability and compromised quality of life in women. Neuropathic mechanisms are believed to play an important role. An imbalanced sympathetic and sensory innervation (reduced sympathetic innervation, with unchanged or increased sensory innervation in endometriotic lesions) has been demonstrated in endometriosis in recent studies. And it is believed to contribute to the pathogenesis of endometriosis-associated pain. It is primarily considered to be a natural adaptive program to endometriosis-associated inflammation. However, it is important to further clarify whether other potential modulating factors are involved in this dysregulation. It is generally accepted that endometriosis is an estrogen dependent disease. Higher estrogen biosynthesis and lower estrogen inactivation in endometriosis can lead to an excess of local estrogen in endometriotic lesions. In addition to its proliferative and anti-inflammatory actions, local estrogen in endometriosis also exerts potential neuromodulatory effects on the innervation in endometriosis. The aim of this review is to highlight the role of estrogen in mediating this imbalanced sympathetic and sensory innervation in endometriosis, through direct and indirect mechanisms on sympathetic and sensory nerves. Theoretical elaboration of the underlying mechanisms provides new insights in supporting the therapeutic role of estrogen in endometriosis-associated pain.