Project Summary/Abstract Timothy Deimling, M.D., M.Sc. is a Minimally Invasive GYN Surgeon with a long-term career goal of developing an integrative clinical-research program for the management of endometriosis. The primary aim of the program is the integration of medical and surgical management of endometriosis. The program will have an increased focus on reduction of endometriosis-associated pain and the development of strategies to decrease opioid use in this at risk population. Endometriosis is a common disease affecting 6-10% of reproductive aged women. The primary symptoms of endometriosis are chronic cyclic pelvic pain and infertility. To date there is no cure for endometriosis and the exact etiology is not clearly understood. There are multiple theories regarding the cause of endometriosis, however, it is known that once present, endometriosis is hormonally responsive, involves pain exacerbated by inflammation and presents chronic recurrent symptoms. Current treatment is focused on decreasing inflammation, medical suppression of menses and surgical excision. This leaves practitioners in a position of long-term symptom management and although first line treatment should be focused on use of hormones to suppress menstruation and the use of anti-inflammatory medications, patients often times use opioid based medications for symptomatic relief. Naltrexone hydrochloride is a competitive opioid antagonist, traditionally used in the treatment of opioid addiction. More recently naltrexone has been evaluated as a novel treatment of chronic pain. For the indication of pain, significantly lower doses are used (~1/10) than in the treatment of addiction--this is often referred to as low dose naltrexone (LDN) treatment. LDN has demonstrated anti-inflammatory benefits in the central nervous system by acting directly on microglia cells and has also demonstrated a paradoxical effect on the opioid receptor. Prior studies suggest that LDN improves symptoms in other chronic inflammatory disorders such as Crohn's disease and fibromyalgia. The immediate goals of the proposed research plan are to conduct a prospective double-blind placebo-controlled trial evaluating the efficacy of LDN in the management of endometriosis-associated pain. We hypothesize that LDN will improve pain symptoms and quality of life in patients with endometriosis, reflected by decreased Visual Analogue Scale (VAS) scores and increased scores on validated quality of life questionnaires when compared to placebo. The study will include a 12- week blinded intervention followed by a six-month optional open label extension period. The career development award (K23) will provide Dr. Deimling with the skills, mentorship, and preliminary data to develop a competitive R01 grant proposal that will allow a more comprehensive evaluation of treatment options such as LDN for minimizing the impact of this disease and reducing the potential for opioid abuse in reproductive aged women.