Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Basic Clin Pharmacol Toxicol. 2020 Feb;126(2):110-115. doi: 10.1111/bcpt.13307. Epub 2019 Aug 17.
Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case-control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55-3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone-binding globulin adrenocorticotropic hormone, insulin-like growth factor-1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment-induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.
二甲双胍被发现可降低女性升高的催乳素水平,但对男性无效。本研究旨在探究内源性睾酮是否决定了二甲双胍对男性泌乳细胞功能的影响。这项前瞻性病例对照研究纳入了 28 名新近诊断为 2 型糖尿病且伴有轻度或中度高催乳素血症的男性患者,其中 14 名患者睾酮水平较低,而其余 14 名患者的睾酮水平处于参考范围之内。所有参与者均接受了为期 4 个月的二甲双胍(2.55-3 g/d)治疗。在研究开始和结束时,测量了两组患者的血糖、胰岛素、催乳素、睾酮、雌二醇、促性腺激素、性激素结合球蛋白、促肾上腺皮质激素、胰岛素样生长因子-1、促甲状腺激素和游离甲状腺激素的循环水平。尽管二甲双胍降低了两组患者的血浆葡萄糖水平并改善了胰岛素敏感性,但在睾酮水平较低的患者中,这种作用更强。只有在睾酮水平异常低的患者中,该药物才会降低催乳素水平。这种作用伴随着黄体生成素水平的升高,与基线睾酮和计算得出的游离睾酮水平呈负相关,与治疗引起的胰岛素敏感性改善呈正相关。在两个治疗组中,二甲双胍对其余激素的血浆水平均产生了中性作用。研究结果表明,内源性睾酮可能会减弱二甲双胍对泌乳细胞的影响。