Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Department of Pediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
J Clin Pharm Ther. 2021 Oct;46(5):1349-1356. doi: 10.1111/jcpt.13447. Epub 2021 Jun 2.
Metformin was found to normalize secretory function of overactive pituitary cells. Its effect on circulating thyrotropin levels was more pronounced in women receiving exogenous vitamin D. The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia.
The study population consisted of three groups of women with prediabetes and elevated prolactin levels: vitamin D-naïve women with vitamin D insufficiency (group 1; n = 19), women receiving vitamin D preparations because of vitamin D deficiency (group 2 n = 20), as well as vitamin D-naïve women with normal vitamin D status (group 3 n = 23). All participants were then treated with metformin (2.55-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin were determined at baseline and six months later.
At baseline, prolactin levels were higher in group 1 than in the remaining groups of patients. Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3. Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels. The impact on prolactin levels correlated with 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin D.
The results of the current study suggest that the impact of metformin on secretory function of overactive lactotropes depends on the vitamin D status of patients.
二甲双胍被发现可使过度活跃的垂体细胞的分泌功能正常化。在接受外源性维生素 D 的女性中，其对循环促甲状腺激素水平的影响更为明显。本研究的目的是研究维生素 D 状态是否决定二甲双胍对患有高催乳素血症的绝经前妇女催乳素水平的影响。
研究人群由三组患有糖尿病前期和催乳素水平升高的妇女组成：维生素 D 缺乏的维生素 D 不足的妇女（第 1 组；n=19），因维生素 D 缺乏而接受维生素 D 制剂的妇女（第 2 组 n=20），以及维生素 D 正常的维生素 D 状态的妇女（第 3 组 n=23）。然后，所有参与者均接受二甲双胍（每天 2.55-3g）治疗。在基线和六个月后测定血糖、胰岛素、催乳素、促甲状腺激素、游离甲状腺激素、促性腺激素、雌二醇、钙和 25-羟维生素水平。
在基线时，第 1 组的催乳素水平高于其余两组患者。尽管二甲双胍降低了所有治疗组的血糖水平并改善了胰岛素敏感性，但这种作用在第 2 组和第 3 组更为明显。仅在 25-羟维生素 D 水平处于参考范围内的受试者中，二甲双胍降低了催乳素水平。对催乳素水平的影响与 25-羟维生素 D 水平以及胰岛素敏感性的改善相关。该药物对循环促甲状腺激素、游离甲状腺激素、促性腺激素、雌二醇、钙和 25-羟维生素 D 水平无影响。
本研究结果表明，二甲双胍对过度活跃的催乳素细胞分泌功能的影响取决于患者的维生素 D 状态。
