Could a common Weight-Loss drug help hormone therapy work better for young women with endometrial cancer?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically confirmed grade 1-2 endometrioid endometrial adenocarcinoma or atypical endometrial hyperplasia (AEH), independently confirmed by two senior pathologists * Lesion confined to the endometrium on MRI or transvaginal ultrasound; FIGO (2009) stage IA without myometrial invasion (for G1, superficial invasion less than one half is allowed; G2 must have no myometrial invasion) * Age 45 years or younger * Received first-line MPA 250-500 mg/day or MA 160-320 mg/day for at least 3 months, with hysteroscopy plus curettage confirming failure to achieve complete response (persistent EC/AEH lesion) * PR-positive cell percentage 25% or less and intensity grade 1 or lower (0 negative, 1 weak, 2 moderate, 3 strong), independently judged by two senior pathologists with a third adjudicating any disagreement * BMI 24 kg/m2 or higher; no severe comorbidity, specifically ALT/AST 2.5x ULN or lower, serum creatinine 1.5x ULN or lower, and no history of active gastrointestinal bleeding * No contraindication to progestin therapy or to pregnancy * No evidence of distant metastasis on pelvic MRI and chest/abdominal CT * Clearly wishes to preserve fertility and provides signed informed consent * No use of orlistat or other lipase inhibitors within the past 6 months * Willing and able to comply with follow-up at this hospital Exclusion Criteria: * Tumor invading more than one half of the myometrium; FIGO (2009) stage IB or higher * Grade G3 or non-endometrioid histology (serous, clear cell, carcinosarcoma, etc.) * Coexisting other endometrial cancer or other reproductive-system malignancy; coexisting breast cancer or other hormone-dependent tumor precluding progestin use * Allergy to orlistat or any formulation component, or prior severe adverse reaction (including severe hepatic injury) to orlistat * Chronic malabsorption syndrome (Crohn disease, celiac disease, short bowel syndrome) or cholestasis * Concurrent use of ciclosporin, warfarin, levothyroxine, antiepileptics (carbamazepine, phenytoin), or amiodarone that interact significantly with orlistat and cannot be replaced or dose-adjusted * Planned bariatric surgery (gastric bypass, sleeve gastrectomy, etc.) during the study * Pregnancy or lactation; unwilling to use reliable contraception during the study and for 3 months after study completion * Poor compliance or unable to complete 24 months of follow-up