Introduction To explore the effect of rosuvastatin combined with oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH).

Methods This was a single-center phase II study with an open-label, single-arm, phase 2 trial conducted between September 2020 and June 2022. We enrolled patients with newly diagnosed untreated AEH and dyslipidemia. Patients received MA 160 mg plus rosuvastatin 10 mg orally daily. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. A Simon two-stage design was used to compare a null hypothesis of <20% response rate against an alternative of 40%.

Results Thirty-six patients were enrolled in the intention-to-treat population with a median BMI of 28.87 kg/m². Thirteen patients (36.1%) had a complete response at 16 weeks of treatment, and the Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) was 36.1% (25.0–45.4%). Considered high BMI in these patients may reduce CR rate, we retrospectively collected data from all newly diagnosed AEH patients with dyslipidemia and MA-treated in our hospital from 2016 to 2022, and the Kaplan-Meier estimate of 16-week CR rates (with 95% CI) was 22.5% (16.6–34.1%). After adjusting for patient age, BMI, insulin resistance, metabolic syndrome and previous medical history, the use of rosuvastatin (HR, 1.130; 95%CI, 1.012–1.263; P=0.031) was significantly correlated with better treatment effects to achieve CR.

Conclusion/Implications Due to higher BMI in study population, our data did not meet the predefined primary outcome. Compared with AEH patients with dyslipidemia using MA alone, the combined use of rosuvastatin did improve the treatment effects.