title: Metformin decreases circulating androgen and estrogen levels in nondiabetic women with breast cancer.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Endocrinological Gynecology, Ospedale Sant'Anna di Torino, Turin, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Campagnoli
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Venturelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Abbà
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.forename: Tiziana
authors.initials: T
authors.lastname: Brucato
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cogliati
authors.forename: Saverio
authors.initials: S
authors.lastname: Danese
authors.forename: Michela
authors.initials: M
authors.lastname: Donadio
authors.forename: Gianna
authors.initials: G
authors.lastname: Zito
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pasanisi
mesh_terms: D000368:Aged; D000728:Androgens / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D003920:Diabetes Mellitus; D004967:Estrogens / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D011379:Prognosis
chemical_list: D000728:Androgens; D004967:Estrogens; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Dehydroepiandrosterone sulfate; Estradiol; IGF1; Randomized trial; Testosterone