title: Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study.
abstract: This is a randomized controlled trial to test the effect of different doses of metformin in patients with breast cancer and without diabetes, with the aim of modifying the hormonal and metabolic parameters linked to breast cancer prognosis. Analysis of the results suggest that the dose of 1500 mg/d of metformin causes a significant reduction of insulin and testosterone serum levels.
  
  
  BACKGROUND
  Serum levels of insulin and testosterone may affect both breast cancer (BC) incidence and prognosis. Metformin reduces hyperglycemia and insulin levels in patients with diabetes. In women without diabetes and with polycystic ovary syndrome, metformin lowers both insulin and testosterone levels. Patients with diabetes who are treated with metformin showed a lower risk of cancer; a protective effect of metformin also was observed for BC. Recently, studies on metformin use for prevention or treatment of BC have been proposed in patients who are not diabetic. The aim of the present study was to test the effect of different doses of metformin on serum levels of insulin and testosterone in those postmenopausal patients with breast cancer and without diabetes who have basal testosterone levels ≥0.28 ng/mL (median value).
  
  
  METHODS
  A total of 125 eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months were invited to continue the study with metformin 1000 mg/d (500 mg twice a day [b.i.d.]) for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose by taking metformin 1500 mg/d (500 mg 3 times a day [t.i.d.]), and the other group continued with metformin 1000 mg /d (500 [b.i.d.]).
  
  
  RESULTS
  A total of 96 women completed the study: 43 women received 1500 mg/d, and 53 women received 1000 mg/d. The women who took 1500 mg/d showed a significant reduction of insulin level, HOMA-IR index (homeostasis model assessment-insulin resistance index), testosterone level, and free androgen index compared with women treated with 1000 mg/d. After treatment with 1500 mg/d, the insulin level decreased by 25% and the testosterone level decreased by 23%.
  
  
  CONCLUSIONS
  Both these changes might have a prognostic importance.
authors.affiliation: Unit of Endocrinological Gynecology, Azienda Ospedaliera OIRM-Sant'Anna Torino, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Campagnoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pasanisi
authors.forename: Chiara
authors.initials: C
authors.lastname: Abbà
authors.forename: Simona
authors.initials: S
authors.lastname: Ambroggio
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.forename: Tiziana
authors.initials: T
authors.lastname: Brucato
authors.forename: Raffaella
authors.initials: R
authors.lastname: Colombero
authors.forename: Saverio
authors.initials: S
authors.lastname: Danese
authors.forename: Michela
authors.initials: M
authors.lastname: Donadio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Venturelli
authors.forename: Gianna
authors.initials: G
authors.lastname: Zito
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D013739:Testosterone / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013739:Testosterone; D008687:Metformin