Canagliflozin Plus Progestin for Atypical Endometrial Hyperplasia and Early-Stage Endometrial Cancer

Prior treatment

• Long-term use of corticosteroids or insulin/insulin sensitizers;
• Active infection, or a history of recurrent urinary tract infections (≥ 3 episodes within the previous 12 months, or ≥ 2 episodes within the previous 6 months);
• Genital tract inflammation within 2 weeks before enrollment, or abnormal vaginal discharge that has not been treated;
• Concomitant malignant tumor at any other site;

Other illness

• History of allergy to LNG-IUS, SGLT2 inhibitors, or metformin, or any contraindication to these treatments;
• Overly large uterine cavity (mean diameter \> 7 cm) or a history of LNG-IUS (Mirena) expulsion;
• History of type 1 diabetes mellitus, diabetic ketoacidosis, peripheral vascular disease, or diabetic foot ulcers;
• Other reproductive disorders;

Lab values

• Type 2 diabetes mellitus requiring insulin therapy, or glycated hemoglobin (HbA1c) \> 8.5% (insulin users are excluded owing to the increased risk of ketoacidosis);
• Severe chronic diseases with cardiac, hepatic, pulmonary, or renal insufficiency (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \> 3 × the upper limit of normal \[ULN\], or serum bilirubin \> 3 × ULN), or renal insufficiency (estimated glomerular filtration rate \[eGFR\] \< 60 ml/min/1.73 m²);

Other

• Baseline blood pressure below 90/60 mmHg;
• Alcohol abuse (\> 20 g/day) or smoking.

• Female, aged 18-45 years, with a definite desire for fertility preservation
• First-time diagnosis of atypical endometrial hyperplasia (AH) or grade 1 endometrioid endometrial carcinoma (G1 EEC), confirmed by pathologists at the study center
• For patients with EEC, MRI or ultrasound confirming that the lesion is confined to the endometrium or invades less than 1/2 of the myometrium, without distant metastasis
• Positive expression of both estrogen receptor (ER) and progesterone receptor (PR)
• Normal hepatic and renal function
• No contraindications to progestin or canagliflozin therapy
• No hormonal therapy or SGLT2 inhibitor treatment lasting more than 1 month within the previous 6 months
• Presence of any of the following: diagnosed polycystic ovary syndrome (PCOS), overweight (BMI ≥ 24), impaired glucose tolerance, or diabetes mellitus
• No other fertility disorders and no contraindications to pregnancy
• Not currently pregnant
• Good compliance, willing to comply with subsequent assessments, treatment, and follow-up, with understanding and signing of the informed consent form