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The aim of the present study was to determine whether physiological levels of oestradiol determine the effect of metformin on hypothalamic\u2013pituitary\u2013thyroid axis activity. The study population included 40 postmenopausal women with prediabetes and untreated non\u2010autoimmune subclinical hypothyroidism, using (group A; n\u00a0=\u00a018) or not using (group B; n\u00a0=\u00a022) oestradiol replacement therapy. Over the entire study periods, all subjects were treated with metformin (2.55\u20133.00\u00a0g 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\u00a0months 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\u2010GT, 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\u2013pituitary\u2013thyroid axis activity depends on the oestrogen status of patients.<\/jats:p>","DOI":"10.1111\/1440-1681.13542","type":"journal-article","created":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T05:23:42Z","timestamp":1624080222000},"page":"1469-1476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The impact of metformin on hypothalamic\u2013pituitary\u2013thyroid axis activity in postmenopausal women with untreated non\u2010autoimmune subclinical hypothyroidism"],"prefix":"10.1111","volume":"48","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 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Kowalcze","sequence":"additional","affiliation":[{"name":"Department of Pediatrics in Bytom School of Health Sciences in Katowice Medical University of Silesia Katowice Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogus\u0142aw","family":"Okopie\u0144","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia Katowice Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0273"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2965"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1210"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2020.1789969"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2016.01.015"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2012.11091432"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0584-0006"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12600"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986707780597943"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(10)70357-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2016.07.002"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-122224"},{"key":"e_1_2_10_14_1","first-page":"164","article-title":"The impact of testosterone on metformin action on hypothalamic\u2010pituitary\u2010thyroid axis activity in men: a pilot study","volume":"60","author":"Krysiak R","year":"2020","journal-title":"J Clin Pharm Ther"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13307"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13105"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0921-6420"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172782"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000367692"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.164"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012512"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-018-2593-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2012.06.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(13)71489-0"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2012.12.011"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu020"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03534.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00057"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0019-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.087023"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-013-0488-y"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-19-0470"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05844"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01524-8"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02763-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1201-y"},{"key":"e_1_2_10_37_1","first-page":"156","article-title":"Polish council for control of iodine deficiency disorders. 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