Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis

Abstract

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.MethodsA systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.ResultsIn total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).ConclusionFor reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.PROSPERO registration numberCRD42020179069.disease remission,

Metformin in Combination with Progesterone Improves the Pregnancy Rate for Patients with Early Endometrial Cancer

“…The insufficient dose of metformin and the heterogeneity of BMI between treatment groups may have some influence on the results of the study, so further research should be carried out for verification [ 18 ]. A meta-analysis by Chae-Kim et al demonstrated that the combination therapy of progesterone and metformin is associated with lower relapse rates and similar remission, clinical pregnancy, and live birth rates for reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer [ 19 ]. Existing studies have manifested that metformin improves the remission rate and reduces the recurrence rate of conservatively treated patients to some extent.…”

Fertility-Sparing Approaches in Atypical Endometrial Hyperplasia and Endometrial Cancer Patients: Current Evidence and Future Directions

“…Chae-Kim et al [ 73 ] recently published a systematic review of progestin therapy combined with metformin for atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. The review included six studies with 621 women, 241 treated with progestin + metformin and 380 treated with progestin only.…”

Multiple attempts at fertility preservation in atypical endometrial hyperplasia and early endometrial cancer

“…A recent meta-analysis examined outcomes after progestin versus progestin with metformin therapy and found that combined therapy was associated with decreased relapse rates. 7 The data on outcomes after metformin fertility-sparing therapy are limited, however, and there is significant heterogeneity in the data regarding the dosing and duration of metformin therapy for those who pursue conservative treatment. Given that evidence is limited, the role of metformin in fertility-sparing treatment is not yet clear and there is uncertainty regarding the patient population for whom metformin is most beneficial, although initial review of the literature suggests promising outcomes.…”