The Effect of Medical Management Following Excisional Surgery for Endometriosis: A Randomized Controlled Trial

The design of this study will be an unblinded randomized controlled trial of medical suppression with once daily Relugolix combination therapy (Rel-CT) following excisional surgery for endometriosis performed by high volume minimally invasive gynecologic surgeons. Women over the age of 18 scheduled to undergo a laparoscopic surgery for endometriosis will be screened and if agree and consented to participate will be randomized to either Rel-CT following surgery or no post-operative hormonal suppression using a block randomization with blocks 2 and 4. The surgeon will not have access to the randomization schedule to reduce selection bias. Inclusion criteria will include: 1) Patients over the age of 18 planning to undergo an elective laparoscopic/robotic procedure for known or suspected endometriosis. Exclusion criteria will include: 1) Patients with known contraindications to REL-CT; 2) Any form of hormonal suppression of endometriosis within the protocol guidelines; 3) Primary language other than English/Spanish; 4) Patients without histologic evidence of endometriosis following their surgical procedure; 5) Patients interested in pregnancy within the 12 months following their surgical procedure.

The primary outcome will be change in Endometriosis Health Profile 30 (EHP-30) score. A preoperative EHP-30 will be completed by all patients enrolled in the study within 4 weeks of their scheduled surgical procedure and then again postoperatively at 1 month, 3 months, and 6 months. Investigators expect that postoperative use of REL-CT will lead to a clinically meaningful improvement in EHP-30 scores compared to surgery alone. In addition, investigators will gather data on our secondary outcomes: These data could be very helpful in informing providers and patients of the utility of medical suppression of endometriosis using REL-CT following surgery.

• 40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate (Drug), also known as Relugolix Combination Therapy (Rel-CT), Myfembree: if randomized to study drug, participants will take one tablet Rel-CT daily following excisional surgery for endometriosis

Primary outcomes

• This study aims to determine if immediate postoperative medical suppression with Regugolix combination therapy (Rel-CT) following excisional surgery for endometriosis is superior to surgery alone. [6 months]: The study will assess quality of life via change in total Endometriosis Health Profile 30 (EHP-30) scores following excisional surgery for endometriosis from baseline to 6 months postoperatively.

Secondary outcomes

• Change in EHP-30 scores between groups stratified by endometriosis stage [6 months]: Comparison of EHP-30 scores according to endometriosis stage of the participant of Rel-CT group to non Rel-Ct treatment group
• Comparison of EHP-30 subscales [6 months]: Comparison of EHP-30 survey subscales in treatment groups.
• Comparison of EHP-30 by superficial vs deep infiltrating types [6 months]: Comparison of EHP-30 scores according to the participant having superficial or deep infiltrating endometriosis post-surgery.
• Reintervention rates between groups [6 months]: Need for surgical reintervention will be assessed between treatment groups.
• Compliance rates for the study drug and office visits following surgery [6 months]: Study drug adherence will be monitored and reported.
• Rates of concomitant adenomyosis [6 months]: Rate of concomitant adenomyosis will be collected and compared between two treatment groups.

Sex: Female, ages: 18 Years to any

Inclusion criteria

* Age ≥ 18 years
* Planning to undergo an elective laparoscopic or robotic procedure for known or suspected endometriosis

Exclusion criteria

-A known contraindication to REL-CT. Contraindications include:

* High risk of arterial, venous thrombotic, or thromboembolic disorder
* Pregnancy Known osteoporosis
* Current or history of breast cancer or other hormone-sensitive malignancies
* Known hepatic impairment or disease
* Undiagnosed abnormal uterine bleeding
* Known hypersensitivity to components of Rel-CT
* The patient did not discontinue hormonal suppression within the required timeline:

Trans-Dermal, Oral Medication, Patch, or Vaginal Ring: day before surgery

Intrauterine Device or Sub-Dermal Implant: removed at surgery

Injectable Medication: at least 12 weeks before surgery

* Primary language other than English/Spanish
* Interested in pregnancy within the 6 months following the surgical procedure.
* If pregnancy test performed during pre-surgical work up is positive, the patient will no longer be a candidate for endometriosis surgery and will therefore not be eligible for the study.
* Patients without histologic evidence of endometriosis following their surgical procedure will be removed from the study prior to receiving the study intervention.
* Patients who undergo a surgical intervention more invasive than the planned laparoscopic or robotic excisional surgery, such as open abdominal surgical repair, will be removed from the study prior to receiving the study intervention.

• Informed Consent Form (PDF, 2025-05-08)

• Jordan Klebanoff, MD, Principal investigator, Main Line Health