Metformin increases mammographic breast density: a randomized controlled trial

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 in women who attended the Breast Clinic for opportunistic BC screening or mild breast symptoms. A total of 151 premenopausal women received 500 mg metformin tablets or a placebo made by the same company, twice a day for 6 months, . All the mammograms were evaluated by two expert radiologists. 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. Conclusion: This clinical trial showed that consumption of metformin 500 mg twice daily for 6 months is associated with a higher mammographic breast density as com- pared 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.