Inclusion Criteria:
* Premenopausal woman between age 18 and 49 years (inclusive) at the time of consent. Menopause is defined as amenorrhea \>1 year unrelated to hormonal suppression.
* History of endometriosis diagnosed by surgery (visual or biopsy confirmed), ultrasound, or MRI within 10 years of study entry
* History of self-reported moderate to severe pelvic pain for ≥ 6 months' duration at time of screening visit.
* Willingness to participate in a relugolix CT drug intervention trial
* Has not used an injectable hormone therapy in the past 6 months (e.g. DepoProvera®, DepoLupron®).
* Willingness to 30-60 day washout interval of oral, vaginal, transdermal, intrauterine hormonal therapies prior to study initiation if applicable
* Willingness to use 2 forms of non-hormonal contraception during the entire duration of the study period or has had a history of a bilateral tubal occlusion procedure at least 3 months prior to screening (tubal ligation or hysteroscopic occlusion method)
* Willing to undergo quantitative sensory testing (QST), fMRI and other study procedures
* Ability to read and speak English to allow for written informed consent, phenotyping, and patient-reported outcomes measures
* Meet criteria to participate in QST and fMRI. These include:
* Normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing
* No contraindications to MRI (e.g., metal implants, claustrophobia)
* Willingness to refrain from pain medications such as NSAIDs, acetaminophen, and opioids for 12 hours prior to neuroimaging and QST
* Willingness to refrain from alcohol and nicotine on day of QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed)
* Willingness to refrain from physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable)
* Able to lie still on their back for 1 hour during MRI
* Weigh 300 pounds or less.
Additional inclusion criteria to proceed with Study Visit 2 and clinical trial:
* \>60% complete entries in daily electronic diary (end-of-day pain, bleeding, fatigue scores)
* Minimum of two menstrual flows separated by a minimum of 21 days (d1 bleed to next d1 bleed) during the washout/screening period
* Moderate-severe non-menstrual pain and dysmenorrhea confirmed with daily electronic diary in the washout/screening period.
Exclusion Criteria:
* Contraindication to the use of relugolix CT (high risk of arterial or venous thrombotic, or thromboembolic disorder, known osteoporosis, current or history of breast cancer or other hormone sensitive malignancy, known hepatic impairment or disease, undiagnosed abnormal uterine bleeding, known hypersensitivity to components of relugolix CT).
* Concurrent participation in other therapeutic trials
* Pregnant, lactating, less than 6 months postpartum, or planning a pregnancy within next 12 months
* Planning pelvic or abdominal surgery during study period
* Prior major surgery in the past 4 months that involves incisions on the abdomen, chest, head, other than a skin biopsy (hysteroscopy, endometrial biopsy is ok to include).
* Planning to initiate a new adjunctive pain treatment during study treatment (e.g. cognitive behavioral therapy, physical therapy, acupuncture). Participants may be enrolled if these treatments are completed prior to trial or using stable therapies.
* History of hysterectomy and/or bilateral oophorectomy
* Clinically significant gynecologic condition such as significant endometrial pathology (e.g. endometrial hyperplasia), persistent ovarian cyst larger than 5 cm, largest uterine dimension \>15 centimeters and not planning an additional intervention or treatment for endometriosis, or another uterine or ovarian condition during the study period. Patients may be enrolled in this study if they were previously successfully treated for these conditions. Patients must have undergone pelvic ultrasound or MRI in the past 6 months, and provide results (or release of records to obtain results)
* History or current evidence of psychosis, current suicide risk or attempt within 2 years of study (note: participants with mood disorders such as depression or anxiety will not be excluded)
* Chronic opioid, alcohol, and/or illicit drug use
* History of substance abuse within past one year
* Unable or unwilling to discontinue opioids analgesics within 48 hours of the dense phenotyping study visits
* Medical conditions that may significantly interfere with relugolix CT efficacy, ability to fully comply or would make it unsafe for participants to take part in the study, including but not limited to: morbid obesity with Body Mass Index \> 45, uncontrolled autoimmune/inflammatory diseases, significant cardiopulmonary disease (e.g., angina, congestive heart failure, uncontrolled hypertension, severe cardiac valvular disease, Chronic Obstructive Pulmonary Disease (COPD), chronic asthma), renal or liver disease (e.g. cirrhosis, hepatitis), uncontrolled endocrine or allergic disorders (e.g., hypothyroidism, diabetes, allergic rhinitis), neurologic conditions (e.g., multiple sclerosis, prior stroke, neurological tumor), severe physical impairment (e.g., blindness, deafness, paraplegia); and active malignancy (any malignancy except for localized dermatologic cancer).
* Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigator would prevent safe or satisfactory completion of the study protocol.
* Individuals receiving or applying for compensation or disability and other aspects associated with potential secondary gain per self-report;
* Additional exclusion that prevent participation in QST and fMRI:
1. Severe claustrophobia precluding MRI and evoked pain testing during scanning;
2. Diagnosed peripheral neuropathy
3. Diagnosed epilepsy
4. Diagnosed or self-reported visual-evoked migraines can participate in study, but will not participate in the visual testing procedures.
5. Weigh \>300 pounds
