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The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55\u20103 g daily). Plasma glucose, insulin, thyroid\u2010stimulating hormone (TSH), total and free thyroid hormones, follicle\u2010stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin\u2010like growth factor\u20101 (IGF\u20101) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1\u2010IR], and glycated hemoglobin [HbA<jats:sub>1c<\/jats:sub>]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA<jats:sub>1c<\/jats:sub> in response to metformin treatment. Although metformin decreased HOMA1\u2010IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (\u221250 \u00b1 20% vs \u221230 \u00b1 15%). Similar relationships were observed for FSH (\u221243 \u00b1 21% vs \u221221 \u00b1 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 \u00b1 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF\u20101. The obtained results indicate that hyperthyroidism enhances the gonadotropin\u2010lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic\u2013pituitary\u2013thyroid axis in case of its overactivity.<\/jats:p>","DOI":"10.1002\/jcph.6144","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T05:20:44Z","timestamp":1728019244000},"page":"318-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Subclinical Hyperthyroidism Enhances Gonadotropin\u2010Lowering Effects of Metformin in Postmenopausal Women"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-2620","authenticated-orcid":false,"given":"Robert","family":"Krysiak","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia  Katowice 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