Metformin for endometrial hyperplasia

Clement, Naomi; Oliver, Thomas RW; Shiwani, Hunain; Sanner, Juliane Rf; Mulvaney, Caroline; Atiomo, William

doi:10.1002/14651858.cd012214

Cited by 8 publications

(7 citation statements)

References 20 publications

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“…Clinically, progesterone agents and levonorgestrel intrauterine devices have been widely used in the treatment of endometrial hyperplasia. However, the side effects and continued risk of recurrence associated with these therapeutic methods have been reported in several studies (94). In a small-scale clinical study, metformin was used in combination with medroxyprogesterone acetate in the treatment of endometrial hyperplasia and EC limited to the endometrium.…”

Section: Clinical Studies Of the Therapeutic Effect Of Metformin On Ecmentioning

confidence: 99%

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

Gao

et al. 2020

Oncol Lett

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The present review aims at reviewing the role of metformin in the treatment of endometrial cancer (EC). According to the literature, excessive estrogen levels and insulin resistance are established risk factors of EC. As a traditional insulin sensitizer and newly discovered anticancer agent, metformin directly and indirectly inhibits the development of EC. The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells. In the indirect mechanism, metformin increases the insulin sensitivity of body tissues and decreases circulating insulin levels. Decreased levels of insulin increase the blood levels of sex hormone binding globulin, which leads to reductions in circulating estrogen and androgens. The aforementioned findings suggest that metformin serves an important role in the treatment of EC. Increased understanding of the mechanism of metformin in EC may provide novel insights into the treatment of this malignancy.

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Section: Clinical Studies Of the Therapeutic Effect Of Metformin On Ecmentioning

confidence: 99%

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

Gao

et al. 2020

Oncol Lett

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“…Hysterectomy in reproductive-age women can be greatly avoided only if conservative therapy is able to achieve satisfactory rates of disease remission and recurrence. Some previous meta-analyses have evaluated the efficacy of metformin in endometrial cancer or endometrial hyperplasia (6,7). 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).…”

Section: Introductionmentioning

confidence: 99%

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

Shao

Zhao

2023

Front. Endocrinol.

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ObjectiveProgestin based therapy is the preferred option for fertility-sparing treatment of reproductive-age women with preserved fertility in endometrial hyperplasia (EH) or early endometrial cancer (EEC). Our objective was to investigate whether metformin could enhance the efficacy of progestin-based therapies by meta-analysis.MethodsWe conducted a meta-analysis of randomized or non-randomized controlled trials by searching of PubMed, Embase, Web of science, and Cochrane database from inception to November 8, 2022. The results of enrolled studies were pooled using meta-analysis to estimate the effect of progestin plus metformin on remission, recurrence, pregnancy rate and live birth rate.ResultsIn the analysis of progestin administered systemically or locally, complete response (CR) was significantly higher in progestin plus metformin versus progestin alone in the EH group (pooled OR 2.08, 95% CI 1.29 to 3.34, P=0.003), in the EEC group (pooled OR 1.86, 95% CI 1.13 to 3.05, P=0.01), but not in EEC and EH group (pooled OR 1.46, 95% CI 0.97 to 2.21, P=0.07). In the analysis of progestin administered systemically, complete response was improved in progestin plus metformin versus progestin alone, in the EH group (pooled OR 2.47, 95% CI 1.45 to 4.21, P=0.0009), in the EEC group (pooled OR 2.09, 95% CI 1.18 to 3.71, P=0.01), and in the EEC and EH group (pooled OR 2.03, 95% CI 1.16 to 3.54, P=0.01). The relapse rates of patients with EEC and EH were not different (pooled OR 0.54, 95% CI 0.24 to 1.20, P=0.13). For obstetric outcomes, the addition of metformin improved pregnancy rate (pooled OR 1.55, 95% CI 0.99 to 2.42, P=0.05), but not live birth rate (pooled OR 0.95, 95% CI 0.45 to 2.01, P=0.89).ConclusionFor fertility-sparing management, compared to progestin alone, the outcomes of patients with endometrial hyperplasia and early endometrial cancer were more improved with progestin plus metformin because progestin plus metformin increases the rate of remission and pregnancy.

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“…Agents under evaluation include oral contraceptives and the use of NSAIDs like aspirin to target inflammation (STICs and STONEs, NCT03480776, under investigation in an interventional trial). A Cochrane meta-analysis assessing the role of metformin in endometrial hyperplasia, found insufficient evidence that differences in regression of endometrial hyperplasia or progression to cancer exist between metformin versus metformin in combination with megestrol acetate versus megestrol acetate alone (5). Epidemiologic studies on diabetic patients and meta-analysis have shown a potential role of metformin in prevention of gynecologic malignancies; however, well-designed randomized interventional studies in diabetic and nondiabetic patients are needed, as patient selection and other biases may have been responsible for lower cancer incidence in patients receiving metformin in observational studies (5,6).…”

mentioning

confidence: 99%

“…A Cochrane meta-analysis assessing the role of metformin in endometrial hyperplasia, found insufficient evidence that differences in regression of endometrial hyperplasia or progression to cancer exist between metformin versus metformin in combination with megestrol acetate versus megestrol acetate alone (5). Epidemiologic studies on diabetic patients and meta-analysis have shown a potential role of metformin in prevention of gynecologic malignancies; however, well-designed randomized interventional studies in diabetic and nondiabetic patients are needed, as patient selection and other biases may have been responsible for lower cancer incidence in patients receiving metformin in observational studies (5,6). A randomized placebo-controlled phase III trial showed low dose metformin was safe and reduced the prevalence and number of colorectal polyps after polypectomy in 1 year in nondiabetic patients (7).…”

mentioning

confidence: 99%

Metformin in Gynecologic Cancers: Opening a New Window for Prevention and Treatment?

Madariaga

Goodwin

Oza

2020

Clinical Cancer Research

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Metformin is an affordable and well-tolerated drug used in type 2 diabetes. Potential anticancer effects of metformin in gynecologic malignancies include inhibition of the PI3K-mTOR pathway, hormone receptor regulation, and reduction of fibrosis and inflammation. Multiple studies are currently assessing its role in cancer prevention and as a treatment enhancer. See related articles by Soliman et al., p. 581, and McCloskey et al., p. 632

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Metformin for endometrial hyperplasia

Cited by 8 publications

References 20 publications

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

Therapeutic effect of metformin in the treatment of endometrial cancer (Review)

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

Metformin in Gynecologic Cancers: Opening a New Window for Prevention and Treatment?

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