The addition of metformin to progestin therapy in the fertility-sparing treatment of women with atypical hyperplasia/endometrial intraepithelial neoplasia or endometrial cancer: Little impact on response and low live-birth rates

• Published in: Gynecologic oncology Vol. 157; no. 2; pp. 348 - 356
• Main Authors: Acosta-Torres, Stefany, Murdock, Tricia, Matsuno, Rayna, Beavis, Anna L., Stone, Rebecca L., Wethington, Stephanie L., Levinson, Kimberly, Grumbine, Francis, Ferriss, J. Stuart, Tanner, Edward J., Fader, Amanda N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2020
• Subjects: Hematology, Oncology, and Palliative Medicine; Obstetrics and Gynecology
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2020.02.008

Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment. A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999–2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models. Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m2, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group. Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART. •Fertility preserving management of endometrial intraepithelial neoplasia and cancer with progestins yields a 79% response.•Combined progestin and metformin therapy does not improve response rate in endometrial intraepithelial neoplasia and cancer.•Combined progestin and metformin therapy may improve complete response rate in endometrial intraepithelial neoplasia.•Few women undergoing fertility preserving management achieve pregnancy.