Unit of Endocrinological Gynecology, Azienda Ospedaliera OIRM-Sant'Anna Torino, Italy.
Clin Breast Cancer. 2012 Jun;12(3):175-82. doi: 10.1016/j.clbc.2012.03.004.
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.
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).
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.]).
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%.
Both these changes might have a prognostic importance.
本研究旨在测试不同剂量二甲双胍对患有乳腺癌且无糖尿病的患者的影响，以期改善与乳腺癌预后相关的激素和代谢参数。方法：这是一项随机对照试验，共纳入 125 名符合条件的绝经后女性患者，这些患者的基础睾酮水平≥0.28ng/mL（中位数）。最初，所有患者均被邀请服用二甲双胍 500mg/d，持续 3 个月。完成前 3 个月治疗的 108 名患者被邀请继续服用二甲双胍 1000mg/d（500mg，每日 2 次）1 个月。然后，将这些患者随机分为两组，在随后的 5 个月中，一组患者增加剂量，服用二甲双胍 1500mg/d（500mg，每日 3 次），另一组患者继续服用二甲双胍 1000mg/d（500mg，每日 2 次）。结果：共有 96 名女性完成了这项研究，其中 43 名女性接受了 1500mg/d 的治疗，53 名女性接受了 1000mg/d 的治疗。与接受 1000mg/d 治疗的女性相比，接受 1500mg/d 治疗的女性的胰岛素水平、HOMA-IR 指数（稳态模型评估-胰岛素抵抗指数）、睾酮水平和游离雄激素指数均显著降低。接受 1500mg/d 治疗后，胰岛素水平下降了 25%，睾酮水平下降了 23%。结论：这些变化可能具有预后意义。
