A multi-center clinical trial is currently underway in China to evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRH-a) combined with letrozole or levonorgestrel-releasing intrauterine device (LNG-IUD) compared to traditional progestogen therapy for fertility-sparing treatment of atypical endometrial hyperplasia (AEH). This study addresses the critical need for effective and safe alternatives to hysterectomy for women with AEH who wish to preserve their fertility.
The trial, registered on 28/08/2023, is a prospective, randomized, controlled study. Participants diagnosed with AEH will be randomly assigned to one of two treatment arms: GnRH-a plus letrozole or LNG-IUD, or classical progestogen therapy (megestrol acetate and/or medroxyprogesterone acetate). The primary endpoint is the cumulative complete response rate at 24 weeks post-treatment initiation. Secondary endpoints include the complete response rate at 3 months, median time to complete response, recurrence rate, pregnancy rate, and safety profiles.
Treatment Regimens and Monitoring
Patients in the combination therapy arm will receive GnRH-a injections alongside either oral letrozole or an LNG-IUD. The progestogen therapy arm will receive oral megestrol acetate or medroxyprogesterone acetate. All participants will undergo regular monitoring, including endometrial biopsies and assessments of adverse events. Adverse events will be managed according to standard clinical practice, with detailed documentation and reporting to the Ethics Review Committee.
Criteria for discontinuing trial treatment include patient refusal, protocol violations, lack of remission by 24 weeks, severe adverse events, or any situation where continuation of the assigned treatment is deemed unsafe by the physician. Follow-up evaluations will continue long-term, with recommendations for hysterectomy after complete remission and childbirth, or close monitoring for recurrence in those desiring future fertility.
Statistical Analysis and Data Management
Interim analyses will be conducted to assess trial progress, safety, and efficacy. Formal data analysis will utilize SPSS Statistics software, employing intention-to-treat analysis and imputation methods to handle missing data. The significance level is set at 0.05, with a 95% confidence interval. A comprehensive data management plan ensures data quality, security, and storage, with routine verifications of electronic case report forms (eCRFs).
Addressing Unmet Needs in AEH Management
AEH represents a precancerous condition of the endometrium, and its incidence is rising. While hysterectomy is often recommended, it is not a viable option for women who desire to maintain their fertility. Current fertility-sparing treatments, such as progestogen therapy, have limitations including variable efficacy and potential side effects. This trial seeks to provide evidence for alternative, potentially more effective, and better-tolerated treatments for AEH, offering women more options for managing their condition while preserving their reproductive potential.
