Metformin decreases circulating androgen and estrogen levels in nondiabetic women with breast cancer

Carlo Campagnoli, Franco Berrino, Elisabetta Venturelli, Chiara Abbà, Nicoletta Biglia, Tiziana Brucato, Patrizia Cogliati, Saverio Danese, Michela Donadio, Gianna Zito, Patrizia Pasanisi

Research output: Contribution to journalArticlepeer-review


Introduction Diabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones. Patients and Methods One hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d. Results Ninety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (-29%) and estradiol (-38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate. Conclusion Metformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.

Original languageEnglish
Pages (from-to)433-438
Number of pages6
JournalClinical Breast Cancer
Issue number6
Publication statusPublished - 2013


  • Dehydroepiandrosterone sulfate
  • Estradiol
  • IGF1
  • Randomized trial
  • Testosterone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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