Krysiak Robert, Kowalcze Karolina, Szkróbka Witold, Okopień Bogusław
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.
Department of Pediatrics in Bytom, Faculty of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland.
Pharmaceutics. 2025 Mar 30;17(4):442. doi: 10.3390/pharmaceutics17040442.
The gonadotropin-lowering effects of metformin were found to be more pronounced in the case of coexisting hyperthyroidism and absent in patients with hypovitaminosis D. Thus, the aim of the current study was to determine whether vitamin D status determines pituitary effects of metformin in individuals with thyroid hyperfunction and elevated gonadotropin levels. This prospective cohort study included three matched groups of postmenopausal women with hyperthyroidism and prediabetes: women with 25-hydroxyvitamin D levels between 50 and 75 nmol/L (uncompensated vitamin D insufficiency), women with 25-hydroxyvitamin D levels between 75 and 150 nmol/L receiving exogenous calciferol due to previously diagnosed vitamin D deficiency/insufficiency (compensated vitamin D deficiency/insufficiency), and calciferol-naïve subjects with 25-hydroxyvitamin D levels between 75 and 150 nmol/L (the control group). Over the entire study period (six months), all the women were treated with metformin. At the beginning and at the end of this study, we determined 25-hydroxyvitamin D, glucose homeostasis markers, gonadotropins, estradiol, progesterone, TSH, free thyroid hormones, prolactin, ACTH, and IGF-1. Before metformin treatment, except for the 25-hydroxyvitamin D levels, there were no between-group differences in the investigated markers. In all the study groups, metformin reduced plasma glucose, HOMA1-IR, glycated hemoglobin, and FSH, but these effects were more pronounced in both groups of women with normal vitamin D status than in women with uncompensated vitamin D insufficiency. The decrease in LH concentration was observed only in patients with compensated vitamin D deficiency/insufficiency and in the control group. There were no differences between the baseline and follow-up levels of the remaining hormones. The impact of metformin on gonadotropin concentrations positively correlated with their baseline values, free thyroid hormone levels, 25-hydroxyvitamin D levels, and metformin-induced changes in HOMA1-IR. Our findings suggest that low vitamin D status impairs the gonadotropin-lowering effects of metformin in individuals with hyperthyroidism.
研究发现，二甲双胍降低促性腺激素的作用在合并甲状腺功能亢进的情况下更为明显，而在维生素D缺乏的患者中则不存在。因此，本研究的目的是确定维生素D状态是否决定二甲双胍对甲状腺功能亢进和促性腺激素水平升高个体的垂体作用。这项前瞻性队列研究纳入了三组匹配的患有甲状腺功能亢进和糖尿病前期的绝经后女性：25-羟基维生素D水平在50至75 nmol/L之间的女性（未补偿的维生素D不足）、因先前诊断为维生素D缺乏/不足而接受外源性钙化醇治疗的25-羟基维生素D水平在75至150 nmol/L之间的女性（补偿的维生素D缺乏/不足）以及25-羟基维生素D水平在75至150 nmol/L之间未服用钙化醇的受试者（对照组）。在整个研究期间（六个月），所有女性均接受二甲双胍治疗。在本研究开始和结束时，我们测定了25-羟基维生素D、葡萄糖稳态指标、促性腺激素、雌二醇、孕酮、促甲状腺激素、游离甲状腺激素、催乳素、促肾上腺皮质激素和胰岛素样生长因子-1。在二甲双胍治疗前，除了25-羟基维生素D水平外，所研究的指标在组间没有差异。在所有研究组中，二甲双胍降低了血糖、HOMA1-IR、糖化血红蛋白和促卵泡激素，但这些作用在维生素D状态正常的两组女性中比在未补偿维生素D不足的女性中更为明显。仅在补偿的维生素D缺乏/不足患者和对照组中观察到促黄体生成素浓度的降低。其余激素的基线水平和随访水平之间没有差异。二甲双胍对促性腺激素浓度的影响与其基线值、游离甲状腺激素水平、25-羟基维生素D水平以及二甲双胍引起的HOMA1-IR变化呈正相关。我们的研究结果表明，低维生素D状态会损害二甲双胍对甲状腺功能亢进个体降低促性腺激素的作用。
