Tehran University of Medical Sciences Basic & Clinical Cancer Research 2228-6527 15 4 2025 01 16 237 244 Sadaf Alipour 2. Breast Diseases Research Center (BDRC), Cancer Institute, Tehran University of Medical Science, Tehran, Iran & Department of Surgery, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran Ladan Hosseini Tehran University of Medical Sciences Zohreh Forootan Tehran University of Medical Sciences Hadith Rastad Alborz University of Medical Sciences Leila Bayani Tehran University of Medical Sciences Mahboubeh Abedi Ballarat Base Hospital Bita Eslami Tehran University of Medical Sciences 2024 07 02 2024 08 10 Background Mammographic breast density (MBD) is directly related to the risk of breast cancer. In vivo and in vitro studies have shown that metformin can reduce the proliferation and growth of breast cancer tissue. The aim of this study was to determine the effect of metformin on MBD in non-diabetic premenopausal women. Methods A double-blind, placebo-controlled study was performed. A total of 151 premenopausal women received 500 mg metformin tablets twice a day for 6 months, or a placebo, were included. The changes in MBD were compared between the two groups. Results Final data were evaluated based on 67 and 84 women in the metformin and placebo groups, respectively. Based on results from Ordinal Logistic Regression, the odds of achieving a higher density for the intervention group was approximately 2.33 (95% CI, 1.04 to 5.18) times that of the placebo group. Conclusions This clinical trial showed that consumption of metformin 500 mg twice daily for 6 months is associated with a higher mammographic breast density as compared to the placebo group. As metformin is used very commonly, we suggest that this medicine should be considered as a probable confounding factor when conducting studies about MBD. https://bccr.tums.ac.ir/index.php/bccrj/article/view/538