SHAPE-ENDO is a prospective observational study conducted at Hospital Universitari de Bellvitge evaluating a multimodal pre-surgical optimization strategy for women with obesity (BMI ≥35) and atypical endometrial hyperplasia or early-stage endometrial cancer. Participants receive standard-of-care interventions including GLP1 RA therapy, levonorgestrel intrauterine device (with or without oral progestins), structured nutrition and exercise programs, and scheduled endometrial surveillance. The study aims to assess whether this multimodal strategy improves metabolic health, promotes weight loss, and increases eligibility for minimally invasive surgery while maintaining oncologic safety during the optimization period. Participants are followed for 12 months with monitoring of anthropometric and metabolic parameters, histological response, quality of life, and treatment adherence. All interventions are part of routine clinical care. Findings from this study may inform future comparative trials evaluating metabolic optimization strategies in patients with obesity and early-stage endometrial cancer.
Obesity is a major risk factor for endometrial cancer and is associated with increased surgical complexity, perioperative morbidity, and reduced eligibility for minimally invasive surgery. In patients with severe obesity, mortality is frequently influenced by metabolic comorbidities rather than cancer progression. Strategies aimed at improving metabolic health and functional status prior to surgery may therefore have important clinical implications. Hormonal therapies such as the levonorgestrel-releasing intrauterine device and systemic progestins are commonly used for disease control in selected patients with atypical endometrial hyperplasia or early-stage endometrioid carcinoma. In parallel, GIP/glucagon-like peptide-1 receptor agonists, including semaglutide or terzipatide, have demonstrated significant weight loss and cardiometabolic benefits. Multimodal prehabilitation approaches combining pharmacologic therapy, nutritional optimization, and structured exercise programs may improve surgical readiness and overall health status. SHAPE-ENDO is a prospective observational cohort study conducted at Hospital Universitari de Bellvitge. The study evaluates a multimodal pre-surgical optimization strategy that includes pharmacologic weight management with semaglutide, hormonal endometrial treatment with levonorgestrel intrauterine device with or without oral progestins, and lifestyle interventions including supervised dietary counseling and exercise programs. Patients undergo scheduled clinical follow-up with metabolic monitoring, imaging, and endometrial sampling according to routine clinical practice. The study aims to evaluate the feasibility and clinical impact of this multimodal optimization strategy in women with obesity and early-stage endometrial disease. Outcomes include metabolic and anthropometric changes, histological response, quality of life, and eligibility for minimally invasive surgery. Data are collected through electronic medical records, laboratory testing, imaging studies, and validated patient-reported outcome questionnaires. The study is approved by the institutional ethics committee and involves only standard-of-care interventions.
Study Type
OBSERVATIONAL
Enrollment
82
Weekly subcutaneous semaglutide titrated up to 2.4 mg according to routine clinical practice to support weight loss and metabolic optimization in patients with BMI ≥35. The medication is not assigned experimentally; it is prescribed by the treating endocrinology team as part of standard care. Data on dosing, tolerance, and adherence are collected prospectively for observational analysis.
Local hormonal therapy using a levonorgestrel-releasing intrauterine device placed as part of standard clinical management for atypical endometrial hyperplasia or low-risk endometrioid carcinoma. Device insertion occurs at baseline or within 14 days, with ultrasound confirmation of placement. This treatment is not assigned experimentally; it is provided based on routine clinical criteria, and data on tolerability, continuation, and local response are collected prospectively.
Systemic hormonal therapy prescribed according to clinical criteria to support local disease control in atypical endometrial hyperplasia or early-stage endometrioid carcinoma. Typical regimens include medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day). Therapy is initiated or escalated when indicated based on tumor burden or suboptimal response to LNG-IUD. These medications are not assigned experimentally; they are standard-of-care treatments, and their use, dosing, tolerance, and outcomes are recorded prospectively.
Personalized hypocaloric diet plan supervised by the clinical nutrition team as part of standard obesity and metabolic management. The program includes caloric restriction based on basal metabolic requirements, with the option of very low-calorie diets (VLCD) for 4-6 weeks in selected cases. Follow-up occurs at regular outpatient visits with recording of weight, BMI, waist circumference, and adherence. This intervention is part of routine clinical care and not assigned experimentally; outcomes are recorded prospectively.
A structured physical exercise program designed to improve functional capacity, aerobic tolerance, and surgical fitness. Program includes supervised or semi-supervised weekly sessions combining aerobic and strength training, typically 3 sessions per week for 30-45 minutes, adapted to baseline performance. The intervention is part of routine clinical care for patients with obesity undergoing surgical preparation and is not assigned experimentally. Data on adherence, tolerance, and functional outcomes are collected prospectively
Scheduled histological surveillance performed at baseline and at follow-up intervals (typically 14 and 28-54 weeks) to assess local tumor status, including complete response, stability, or progression. Procedures include outpatient endometrial biopsy with optional hysteroscopy based on clinical indication. These evaluations form part of standard clinical care in patients managed conservatively for atypical endometrial hyperplasia or early-stage endometrioid carcinoma and are not assigned experimentally. Data are recorded prospectively to assess disease evolution and surgical eligibility.
Radiologic evaluation using pelvic MRI and transvaginal ultrasound performed as part of routine clinical care to assess uterine disease, myometrial invasion, adnexal status, and treatment response. Imaging is typically performed at baseline to confirm staging and during follow-up when clinically indicated. These imaging modalities are used per standard clinical guidelines and are not assigned experimentally; results are collected prospectively to evaluate disease stability and surgical planning.
Proportion of patients achieving predefined metabolic and clinical optimization criteria
Optimization is defined as achieving ≥10% total body weight loss and/or reduction to BMI \<35 without evidence of tumor progression on histologic or radiologic assessment, enabling eligibility for minimally invasive surgery. Metabolic parameters (weight, BMI, waist circumference, HbA1c, blood pressure, and lipid profile) are recorded longitudinally. Progression is assessed through scheduled endometrial biopsy and imaging.
Time frame: Up to 12 months
Change in Glycated Hemoglobin (HbA1c)
Change from baseline in glycated hemoglobin (HbA1c, %) measured using standard clinical laboratory assays as a marker of glycemic control and cardiometabolic risk.
Time frame: Baseline to 6 months and Baseline to 12 months
Histological Complete Response Rate of Endometrial Lesion
Percentage of patients achieving complete histological response of the endometrial lesion assessed by endometrial biopsy with or without hysteroscopy. Histological evaluation is performed by gynecologic pathologists using standardized pathological criteria. Complete response is defined as absence of endometrial carcinoma or atypical hyperplasia on biopsy during follow-up. Unit of Measure: Percentage of patients (%).
Time frame: Baseline to 6 months and 12 months
Proportion of patients reaching eligibility for minimally invasive surgery
Proportion of patients who meet predefined clinical criteria for minimally invasive hysterectomy after multimodal optimization, including adequate metabolic improvement, anesthetic clearance, functional capacity, and absence of disease progression on pathology or imaging. Eligibility is determined by the multidisciplinary tumor board and surgical team.
Time frame: Up to 12 months
Change in Health-Related Quality of Life Score (SF-36)
Change from baseline in health-related quality of life assessed using the Short Form-36 Health Survey (SF-36) questionnaire. The SF-36 evaluates multiple domains of physical and mental health. Scores range from 0 to 100, with higher scores indicating better health-related quality of life..
Time frame: Baseline to 12 months
Incidence of adverse events related to standard-of-care treatments
Frequency, severity, and type of adverse events associated with standard-of-care treatments, including semaglutide and hormonal therapy. Events are documented through clinical records and routine follow-up visits, classified according to CTCAE criteria, and categorized as mild, moderate, severe, serious, or treatment-limiting. Only events occurring during active management and follow-up are included
Time frame: Baseline to 12 months
Perioperative outcomes following minimally invasive surgery
Perioperative outcomes in patients who undergo minimally invasive hysterectomy after optimization, including operative time, estimated blood loss, conversion to laparotomy, intraoperative complications, hospital stay, 30-day postoperative complications, and readmission. Complications will be graded according to Clavien-Dindo classification.
Time frame: At time of surgery and 30 days postoperatively
Changes in anthropometric measures (BMI, waist circumference, visceral adiposity)
Change in BMI, waist circumference, and percent weight loss categories (≥5%, ≥10%, ≥15%). Measurements taken at scheduled visits and analyzed longitudinally to evaluate response to multimodal optimization.
Time frame: Up to 12 months
Adherence to GLP-1 therapy, hormonal therapy, diet, and exercise interventions
Adherence to semaglutide, hormonal therapy (LNG-IUD ± oral progestins), dietary plan, and structured exercise program, including reasons for modification or discontinuation. Data obtained from clinical records, pharmacy dispensation, and self-reported logs.
Time frame: Baseline to 12 months
Change in Fasting Plasma Glucose
Change from baseline in fasting plasma glucose concentration (mg/dL) measured using standard biochemical laboratory analysis.
Time frame: Baseline to 6 months and Baseline to 12 months
Change in Serum Triglycerides
Change from baseline in serum triglyceride levels (mg/dL) measured using routine clinical laboratory lipid panel testing.
Time frame: Baseline to 6 months and Baseline to 12 months
Change in HDL Cholesterol
Change from baseline in high-density lipoprotein (HDL) cholesterol levels (mg/dL) measured using standard lipid panel testing.
Time frame: Baseline to 6 months and Baseline to 12 months
Change in LDL Cholesterol
Change from baseline in low-density lipoprotein (LDL) cholesterol levels (mg/dL) measured using standard lipid panel testing.
Time frame: Baseline to 6 months and Baseline to 12 months
Change in Blood Pressure
Change from baseline in systolic and diastolic blood pressure (mmHg) measured using standard clinical sphygmomanometry during routine clinical visits
Time frame: Baseline to 6 months and Baseline to 12 months
Change in C-Reactive Protein (CRP)
Change from baseline in serum C-reactive protein concentration (mg/L) measured using standard laboratory assays as a marker of systemic inflammation.
Time frame: Baseline to 6 months and Baseline to 12 months
Change in Quality of Life Score (EORTC QLQ-C30)
Change from baseline in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The questionnaire evaluates global health status, functional scales, and symptom scales in oncology patients. Scores range from 0 to 100 according to EORTC scoring guidelines.
Time frame: Baseline to 12 months
Change in Functional Capacity
Change from baseline in functional capacity assessed using standardized physical activity tolerance or performance measures recorded during clinical follow-up visits.
Time frame: Baseline to 12 months
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