Trial reportJournal of the National Cancer Institute2021
The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32.
Trial report in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Knowledge mapping of metformin use on cancers: a bibliometric analysis (2013-2023).Frontiers in pharmacology · 2024Pooled it
- Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Pooled it
- Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.Scientific reports · 2025Trial
- The effects of exercise and diet on sex steroids in breast cancer survivors.Endocrine-related cancer · 2022Trial
- Trial
- Metformin in the management of fibrocystic breast disease: a placebo-controlled randomized clinical trial.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2021Trial
- Metformin for the treatment of breast cancer: a scoping review of randomized clinical trials.BMC cancer · 2025Article
- Inhibition of Cyclin D1 by Novel Biguanide Derivative YB-004 Increases the Sensitivity of Bladder Cancer to Olaparib via Causing G0 / G1 Arrest.International journal of biological sciences · 2025Article
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Clinical significance of lipid pathway-targeted therapy in breast cancer.Frontiers in pharmacology · 2024Article
- Metformin: A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation.Journal of pharmaceutical analysis · 2024Article
- Current status and frontier tracking of clinical trials on Metformin for cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- Are steroid hormones and autistic traits affected by metformin? First insights from a pilot.Comprehensive psychoneuroendocrinology · 2023Article
- Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK.American journal of physiology. Heart and circulatory physiology · 2023Article
- Obesity promotes breast epithelium DNA damage in women carrying a germline mutation inScience translational medicine · 2023Article
- Effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women: a pilot study.European journal of clinical pharmacology · 2023Article
- A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- RETRACTED: Metformin and Breast Cancer: Where Are We Now?International journal of molecular sciences · 2022Review
- Hyperinsulinemia in Obesity, Inflammation, and Cancer.Diabetes & metabolism journal · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 20 institutions in 5 countries.
Funding
Abstract
backgroundMetformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones. We evaluated the effect of metformin on sex hormones in MA.32, a phase III trial of nondiabetic BC subjects who were randomly assigned to metformin or placebo.
methodsWe studied the subgroup of postmenopausal hormone receptor-negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after being randomly assigned. Sex hormone-binding globulin, bioavailable testosterone, and estradiol levels were assayed using electrochemiluminescence immunoassay. Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models.
results312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2-negative BC and had received (neo)adjuvant chemotherapy. Mean age was 58.1 (SD=6.9) vs 57.5 (SD=7.9) years, mean body mass index (BMI) was 27.3 (SD=5.5) vs 28.9 (SD=6.4) kg/m2 for metformin vs placebo, respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (-5.7 vs 0 pmol/L; P < .001) in univariable analysis and after controlling for baseline BMI and BMI change (P < .001). There was no change in sex hormone-binding globulin or bioavailable testosterone.
conclusionMetformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.