Vitamin D Status Determines Metformin Action on Gonadotropin Levels in Postmenopausal Women with Subclinical Hyperthyroidism

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> Our findings suggest that low vitamin D status impairs the gonadotropin-lowering effects of metformin in individuals with hyperthyroidism.