ArticleAmerican journal of obstetrics and gynecology2013
Chemopreventive effects of metformin on obesity-associated endometrial proliferation.
Article in American journal of obstetrics and gynecology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis.BMC cancer · 2018Pooled it
- A Randomized Clinical Trial of Levonorgestrel Intrauterine System with or without Metformin for Treatment of Endometrial Hyperplasia without Atypia in Indian Women.Asian Pacific journal of cancer prevention : APJCP · 2021Trial
- Prospective Randomized Biomarker Study of Metformin and Lifestyle Intervention for Prevention in Obese Women at Increased Risk for Endometrial Cancer.Cancer prevention research (Philadelphia, Pa.) · 2018Trial
- A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.Gynecologic oncology · 2025Article
- Metformin exerts anti-AR-negative prostate cancer activity via AMPK/autophagy signaling pathway.Cancer cell international · 2021Article
- Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer.Pathology oncology research : POR · 2021Article
- Fertility-Sparing Treatment for Early-Stage Cervical, Ovarian, and Endometrial Malignancies.Obstetrics and gynecology · 2020Review
- Review
- Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis.Journal of clinical medicine · 2019Review
- Insulin glargine affects the expression ofIranian journal of basic medical sciences · 2018Article
- Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile.Endocrine connections · 2018Article
- Role of metformin in inhibiting estrogen-induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells.Oncology letters · 2017Article
- Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer: A retrospective study.Medicine · 2017Article
- Metformin Accumulation Correlates with Organic Cation Transporter 2 Protein Expression and Predicts Mammary Tumor RegressionCancer prevention research (Philadelphia, Pa.) · 2017Article
- Metformin targets multiple signaling pathways in cancer.Chinese journal of cancer · 2017Review
- Lean Body Weight and Metformin Are Insufficient to Prevent Endometrial Hyperplasia in Mice Harboring Inactivating Mutations in PTEN.Oncology · 2017Article
- Clinical benefits of metformin in gynecologic oncology.Oncology letters · 2015Article
- Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer.Cancer medicine · 2015Article
- Article
- Old drug, new trick: repurposing metformin for gynecologic cancers?Gynecologic oncology · 2014Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectiveObesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. STUDY
designZucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro.
resultsStreptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner.
conclusionThese findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women.
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Registered trials
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