Impaired Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women with Autoimmune Thyroiditis: A Pilot Study

Abstract

Metformin has been found to reduce elevated gonadotropin levels. Hashimoto's thyroiditis is the most common thyroid disorder in iodine-sufficient areas, and it often develops in postmenopausal women. The aim of this study was to investigate whether autoimmune thyroiditis determines the impact of metformin on gonadotrope secretory function. Two matched groups of postmenopausal women were studied: 35 with euthyroid Hashimoto's thyroiditis (group A) and 35 without thyroid disorders (group B). Throughout the study, all participants received oral metformin (2.55-3 g daily). Plasma glucose, insulin, gonadotropins, estradiol, progesterone, thyrotropin, free thyroid hormones, prolactin, adrenocorticotropic hormone, insulin-like growth factor-1, hsCRP, thyroid peroxidase, and thyroglobulin antibody titers were measured at the beginning of the study and six months later. At entry, both groups differed in thyroid peroxidase antibody titers, thyroglobulin antibody titers, and hsCRP levels. In group A, baseline antibody titers correlated positively with hsCRP and negatively with insulin sensitivity. Although metformin improved glucose homeostasis and reduced hsCRP levels in both study groups, these effects were more pronounced in group B than in group A. Only in group B did metformin decrease FSH levels and tend to reduce LH levels. Thyroid antibody titers and the levels of the remaining hormones did not change throughout the study. The impact of metformin on gonadotropin levels correlated with their baseline values and the degree of improvement in insulin sensitivity, as well as with the baseline and treatment-induced reduction in hsCRP. Moreover, the impact on gonadotropins and insulin sensitivity in group A depended on baseline antibody titers. The obtained results indicate that coexisting autoimmune thyroiditis impairs the gonadotropin-lowering effects of metformin in postmenopausal women.

Keywords: FSH; LH; autoimmunity; insulin resistance; menopause; metformin; pituitary; thyroid.