The impact of metformin on hypothalamic-pituitary-thyroid axis activity in postmenopausal women with untreated non-autoimmune subclinical hypothyroidism.

Metformin was found to reduce elevated thyrotropin levels in subjects with hypothyroidism. The impact on thyrotropin levels was stronger in women receiving oral contraceptive pills than in women not using any contraception. The aim of the present study was to determine whether physiological levels of oestradiol determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity. The study population included 40 postmenopausal women with prediabetes and untreated non-autoimmune subclinical hypothyroidism, using (group A; n = 18) or not using (group B; n = 22) oestradiol replacement therapy. Over the entire study periods, all subjects were treated with metformin (2.55-3.00 g daily). Plasma levels of glucose, lipids, insulin, thyrotropin, free thyroxine, free triiodothyronine, prolactin, gonadotropins and oestradiol were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning of the study and 6 months later. At entry, both groups differed in gonadotropin and oestrogen levels. Despite improving insulin sensitivity, thyrotropin levels and Jostel's thyrotropin index in both study groups, these effects were stronger in group A than group B. Only in group A, metformin increased SPINA-GT, while only in group B the drug decreased FSH levels. Levels of the other variables remained at a similar level throughout the study. The effect of treatment on thyrotropin levels correlated with its baseline values, as well as with the improvement of insulin sensitivity. The results obtained suggest that the impact of metformin on hypothalamic-pituitary-thyroid axis activity depends on the oestrogen status of patients.