Clinical Research Directory

Inclusion Criteria: * Female participants aged 18 to 45 years. * Participants have a clear desire to preserve fertility, fully understand that fertility-sparing treatment is not the standard radical treatment for endometrial cancer, are willing to accept the potential risks of disease progression or recurrence associated with delayed radical surgery, and are able to comply with close follow-up as required by the protocol. * Histologically confirmed disease meeting one of the following criteria: atypical endometrial hyperplasia; or FIGO grade 1 endometrioid endometrial cancer meeting FIGO 2023 stage IA1, with disease confined to the endometrium or an endometrial polyp and no myometrial invasion. * Imaging confirms disease confined to the endometrium, with no evidence of myometrial invasion, adnexal involvement, extrauterine disease, or distant metastasis. * Estrogen receptor-positive disease. * Molecular pathology requirements are fulfilled for participants with endometrial cancer, including exclusion of the p53-abnormal molecular subtype. For participants with POLE-ultramutated or mismatch repair-deficient tumors, suitability for fertility-sparing treatment should be determined based on age, family history, genetic findings, and multidisciplinary assessment. Genetic counseling, germline testing, or additional molecular testing may be performed when clinically indicated. * No contraindication to progestin therapy. * Uterine cavity suitable for LNG-IUS placement. * Completed baseline fertility assessment; after complete response, a specific pregnancy plan should be developed after evaluation by reproductive specialists. * BMI ≥28 kg/m2, or BMI ≥24 kg/m2 with at least one weight-related comorbidity, such as hyperglycemia, hypertension, dyslipidemia, fatty liver disease, or obstructive sleep apnea. * No contraindication to mazdutide. * No contraindication to LNG-IUS. * Able to understand and sign informed consent and willing to comply with all study treatments, assessments, and follow-up procedures. Exclusion Criteria: * Pathological diagnosis not consistent with atypical endometrial hyperplasia or eligible early endometrioid endometrial cancer; endometrioid carcinoma grade 2 or higher; or p53-abnormal molecular subtype. * Imaging or pathological evidence of myometrial invasion, ovarian malignancy, extrauterine disease, or distant metastasis. * Prior fertility-sparing drug therapy or intrauterine progestin therapy for atypical endometrial hyperplasia or endometrial cancer. * Use of hormonal therapy or GLP-1 receptor agonists within 6 months before enrollment. * Pregnancy or breastfeeding at enrollment. * Request for hysterectomy or treatment other than conservative medical therapy. * Active pelvic inflammatory disease, recurrent pelvic inflammatory disease, or lower genital tract infection. * Cervical dysplasia or congenital or acquired uterine abnormalities, including fibroids that distort the uterine cavity. * Uterine cavity too large for adequate LNG-IUS coverage or history of LNG-IUS expulsion. * Known hypersensitivity to mazdutide, any of its excipients, or LNG-IUS materials. * History of malignancy at another site. * Uncontrolled clinically significant comorbidities or medical history that may increase study risk or interfere with study evaluation, including cardiovascular, cerebrovascular, thromboembolic, hepatic, renal, coagulation, endocrine, psychiatric, pancreatic, biliary, or severe gastrointestinal disorders. * Diabetes diagnosed by oral glucose tolerance test. * Secondary obesity or endocrine disorders that may affect body weight or metabolic assessment. * Contraindications or major risk factors related to GLP-1 receptor agonist therapy, including pancreatitis, clinically significant gallbladder disease, severe gastrointestinal motility disorder, medullary thyroid carcinoma, or multiple endocrine neoplasia type 2. * Participation in another interventional clinical trial. * Any condition that, in the investigator's opinion, may increase risk during study treatment, interfere with safety assessment, or affect interpretation of study results.