Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer
Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer
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DOI：
10.1016/j.clbc.2013.08.012
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发表时间：
2013-12-01
影响因子：
3.1
通讯作者：
Pasanisi, Patrizia
中科院分区：
文献类型：
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作者：
Campagnoli, Carlo;Berrino, Franco;Pasanisi, Patrizia
这些是来自一项随机对照试验的进一步数据，该试验旨在测试不同剂量的二甲双胍对乳腺癌（BC）和非糖尿病患者的影响，目的是修改与BC预后相关的激素参数。二甲双胍1500 mg/d的剂量导致游离睾酮和雌二醇水平显著降低。简介：二甲双胍治疗的糖尿病患者发生BC的风险较低或BC预后较好。二甲双胍可能通过直接的抗增殖作用或通过间接的机制，特别是减少胰岛素，来减少癌症的生长。在一项对自然绝经且睾酮水平较高的非糖尿病BC患者进行的随机研究中，我们观察到二甲双胍1500 mg/d与1000 mg/d相比，胰岛素和睾酮水平显著降低。我们提出了一个新的分析我们的研究二甲双胍对性激素的生物利用度的影响的结果。患者和方法：124名符合条件的女性最初被邀请服用二甲双胍500 mg/d，持续3个月。完成前3个月的108名女性继续使用1000 mg/d的研究1个月。然后将这些妇女随机分为2组，在随后的5个月里，一组将剂量增加到1500 mg/d，另一组继续1000 mg/d。结果：96名女性完成了研究，43名接受二甲双胍1500 mg/天，53名接受1000 mg/天。接受1500 mg/d的女性显示游离睾酮（-29%）和雌二醇（-38%）的更大和显著降低，雌酮和胰岛素样生长因子-1的边缘显著降低，雄烯二酮的降低不显著。他们还显示硫酸脱氢表雄酮无显著增加。结论：二甲双胍不干扰硫酸脱氢表雄酮的合成。此外，它降低雌二醇水平，基本上是通过减少睾酮。这些激素变化可能具有临床意义。(C)2013 Elsevier Inc. All rights reserved.
These are further data from a randomized controlled trial designed to test the effect of different doses of metformin in patients with breast cancer (BC) and without diabetes, with the aim of modifying the hormonal parameters linked to BC prognosis. A dose of 1500 mg/d of metformin causes significant reductions of the levels of free testosterone and estradiol.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. (C) 2013 Elsevier Inc. All rights reserved.