Metformin as a New Perspective in the Medical Management of Breast Fibroadenoma; A Randomized Clinical Trial Study

Background: Fibroadenoma (FA) is the most common benign solid breast mass in women with no definite method of management. Because fibroadenoma is dependent on female sex hormones, we investigated the effects of metformin, a safe hypoglycemic agent with anti-estrogenic and anti-proliferative properties, in the management of fibroadenoma. Methods: In this randomized clinical trial study, eligible women with fibroadenomas were assigned randomly to the metformin (1000 mg daily), or the placebo group. Breast physical and ultrasound exam was performed before and after the intervention, and the changes in the size of fibroadenomas were compared in the two groups. Results: Overall, 83 patients in the treatment, and 92 in the placebo group completed the study. The mean age of participants was 39.65±10.30 years. The amount of reduction in the size of FA was two-fold in the treatment than placebo group. We categorized size changes of FAs into < 20% enlargement (success) and ≥ 20% enlargement (failure). The odds ratio (OR) for success was 1.48 (95% CI=1.10-1.99) in the treatment group in comparison with the placebo group; and the odds for success was higher in women with multiples fibroadenomas (OR=4.67, 95% CI: 1.34-16.28). Also, the rate of disappearance of fibroadenomas in the treatment group was two-fold higher than the placebo group, although the difference was not statistically significant. Conclusion: This is the first study that evaluates the effect of MF on the management of fibroadenoma, and the results suggest a favorable effect. Larger studies including only large lesions and using higher doses of metformin are suggested to confirm these results. Trial Registration: This trial (IRCT20100706004329N7) was retrospectively registered on 2018-10-07.