Endometriosis is a chronic, estrogen-dependent inflammatory disease influenced by complex neuroimmune interactions and pain chronification mechanisms. Modern medical management is increasingly guided by a deeper understanding of neuroinflammation, peripheral and central sensitization, and immune dysregulation, moving beyond traditional hormonal suppression. This chapter will synthesize the latest evidence on precision medicine approaches, integrating pain phenotyping, molecular and inflammatory biomarkers, and mechanisms of treatment resistance. It will explore targeted pharmacologic strategies, including neuromodulators, selective progesterone receptor modulators, immunomodulatory and anti-fibrotic agents, as well as innovative non-hormonal therapies under investigation. Additionally, it will highlight research gaps and opportunities for translational applications. The aim is to provide a rigorous, mechanism-based framework for individualized, effective, and biologically informed medical treatment of endometriosis.

V-NOSE en bloc laparoscopic hysterectomy with segmental bowel resection for deep infiltrating endometriosis (#ENZIAN C3) - Facts, Views and Vision in ObGyn

Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10–15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.

Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10-15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.