Metformin-induced reduction in prolactin levels is more pronounced in users of hormonal contraception than in non-users. The current study was aimed at investigating whether physiological concentrations of estradiol determine the impact of metformin on lactotrope secretory function.
We studied two matched groups of postmenopausal women with elevated prolactin levels. Twenty-three women were on hormone replacement therapy (group 1), while the remaining ones (group 2, n = 23) did not use sex hormones. Because of coexistent prediabetes, all individuals received metformin (2.55-3 g daily) for the following six months. Circulating levels of total prolactin, monomeric prolactin, thyrotropin, gonadotropins, free thyroid hormones and estradiol were determined at the beginning and at the end of the study.
Compared with group 1, group 2 was characterized by higher gonadotropin levels and lower estrogen levels. Although metformin reduced monomeric prolactin levels in both study groups, this effect was more pronounced in group 1 than in group 2. Only in group 1, metformin decreased total prolactin levels, while only in group 2 the drug reduced FSH levels. Metformin treatment did not affect circulating levels of the remaining hormones. The impact of metformin on total and monomeric prolactin levels correlated with baseline prolactin levels and with the degree of improvement in insulin sensitivity.
The obtained results indicate that the impact of metformin on lactotrope secretory function is partially determined by the estrogen status of patients.

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