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

Abstract

Objective. To study the therapeutic effects of metformin in combination with medroxyprogesterone in the early endometrial cancer patients with fertility requirements. A total of 120 patients with early endometrial cancer admitted to and treated in our hospital were enrolled and evenly assigned into two groups according to different therapeutic regimens, namely, metformin group (metformin combined with medroxyprogesterone acetate) and control group (medroxyprogesterone acetate alone). The objective response rate (ORR) and disease control rate (DCR) were 71.7% (43/60) and 90.0% (54/60) in the metformin group and 53.3% (32/60) and 78.3% (47/60) in the control group, respectively. Adverse reactions such as gastrointestinal reaction, headache, and insomnia were mainly observed in patients. The body mass index (BMI) declined from (34.43 ± 4.34) kg/m2 to (24.77 ± 2.39) kg/m2 in the metformin group and from (33.37 ± 4.49) kg/m2 to (31.28 ± 3.55) kg/m2 in the control group after treatment. After treatment, serum levels of vascular endothelial growth factor (VEGF), angiotensin-2 (Ang-2), carbohydrate antigen 125 (CA125), and CA19-9 in the metformin group were significantly lower than those in the control group (P = 0.005, P < 0.001, P = 0.002, and P < 0.001). During follow-up, the pregnancy rate was 81.7% (49/60) in the metformin group and 61.7% (37/60) in the control group, and the former was prominently higher than the latter (P = 0.025). Metformin in combination with progesterone is effective in treating early endometrial cancer patients with fertility requirements, which significantly reduced the BMI of patients and increased the pregnancy rate after treatment.

Progestin plus metformin improves outcomes in patients with endometrial hyperplasia and early endometrial cancer more than progestin alone: a meta-analysis

“…Among the 13 studies, 1 study was presented as a conference in 2020 ( 19 ), and finally as an article in 2023 ( 20 ), and 5 studies enrolled both patients with EH and patients with EEC ( 19 – 24 ), and 5 studies focused only on patients with EH ( 8 , 11 , 12 , 25 , 26 ), and 2 studies enrolled only patients with EEC ( 9 , 10 ). Six studies were prospective trials ( 9 , 11 , 12 , 23 , 26 , 27 ), while seven were retrospective trials ( 8 , 10 , 19 – 22 , 24 , 25 ). The study published by Matsuo et al.…”

“…In 2017, a cochrane systematic review reported that there is insufficient evidence to support or refute the use of metformin alone or in combination with progestin (7); In 2021, a meta-analysis published by Jennifer Chae-Kim et al showed that the addition of metformin to a progestin-based therapy reduced the rate of disease recurrence, but it failed to improve remission rates, pregnancy rates and live birth rates in patients (6). However, recent studies demonstrated that progestin plus metformin could improve both the rate of disease remission in endometrial hyperplasia (8) and in early endometrial cancer (9). Recently, with the publication of several studies (8)(9)(10)(11)(12)(13), it is essential to further evaluate whether metformin is beneficial in improving the prognosis of endometrial cancer and endometrial hyperplasia.…”

“…However, recent studies demonstrated that progestin plus metformin could improve both the rate of disease remission in endometrial hyperplasia (8) and in early endometrial cancer (9). Recently, with the publication of several studies (8)(9)(10)(11)(12)(13), it is essential to further evaluate whether metformin is beneficial in improving the prognosis of endometrial cancer and endometrial hyperplasia. This meta-analysis is intended to integrate recent clinical studies to assess the benefits of metformin combination with progestin therapy in women suffering from early endometrial cancer or endometrial hyperplasia.…”

Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis

“…Among the selected trials, nine were conducted in China (11,13,15,16,(25)(26)(27)(28)(29), four in the United States (30)(31)(32)(33), three in the United Kingdom (34-36), two in Norway (37,38), two in Italy (39,40), and one each in Poland (41), Australia (42), Russia (43), Germany (44), Belgium (45), Iran (46), and the former Soviet Union (47). Of these, 11 trials investigated the effects of progestin-based combination therapy versus progestin alone or other treatments (11,13,15,16,25,27,28,31,32,42,43), another 11 trials explored the efficacy of progestin alone versus non-progestin treatments (26, 30, 33-35, 37, 40, 41, 44, 45, 47), and 5 trials compared the efficacy of different progestin treatments used alone (29,36,38,39,46). Most studies incorporated two or more outcome indicators, while a few focused solely on a single survival metric, Overall Survival (OS) (33,34,37,41,43,…”

“…weight gain, are frequently observed, impacting therapeutic efficacy and patient compliance (13). Additionally, a potential consequence of progestin therapy is the reduction in progestin receptor concentration, leading to a shorter duration of response (14).…”