{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T23:12:24Z","timestamp":1774653144544,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T00:00:00Z","timestamp":1687564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia in Katowice"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Metformin has been found to reduce elevated gonadotropin levels. Hashimoto\u2019s 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\u2019s thyroiditis (group A) and 35 without thyroid disorders (group B). Throughout the study, all participants received oral metformin (2.55\u20133 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.<\/jats:p>","DOI":"10.3390\/ph16070922","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T05:39:13Z","timestamp":1687757953000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impaired Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women with Autoimmune Thyroiditis: A Pilot Study"],"prefix":"10.3390","volume":"16","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, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0674-5612","authenticated-orcid":false,"given":"Marcin","family":"Basiak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Machnik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, 40-752 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, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhou, J., Massey, S., Story, D., and Li, L. (2018). Metformin: An old drug with new applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102863"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jcph.373","article-title":"The effect of metformin on the hypothalamic-pituitary-thyroid axis in women with polycystic ovary syndrome and subclinical hypothyroidism","volume":"55","author":"Krysiak","year":"2015","journal-title":"J. Clin. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E143","DOI":"10.1210\/jc.2013-2965","article-title":"Effects of treatment with metformin on TSH levels: A meta-analysis of literature studies","volume":"99","author":"Lupoli","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s12020-014-0428-2","article-title":"The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: A pilot study","volume":"49","author":"Krysiak","year":"2015","journal-title":"Endocrine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.psychres.2016.01.031","article-title":"Adjunctive metformin for antipsychotic- induced hyperprolactinemia: A systematic review","volume":"237","author":"Bo","year":"2016","journal-title":"Psychiatry Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1055\/a-0584-0006","article-title":"The effect of metformin on serum gonadotropin levels in postmenopausal women with diabetes and prediabetes: A pilot study","volume":"126","author":"Krysiak","year":"2018","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_7","first-page":"1432","article-title":"The impact of metformin on prolactin levels in postmenopausal women","volume":"46","author":"Krysiak","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"180","DOI":"10.17305\/bjbms.2013.2359","article-title":"Evaluation of endocrine changes in women with the polycystic ovary syndrome during metformin treatment","volume":"13","year":"2013","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/09513590902770172","article-title":"Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome","volume":"25","author":"Billa","year":"2009","journal-title":"Gynecol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/fcp.12600","article-title":"Plasma gonadotropin levels in metformin-treated men with prediabetes: A non-randomized, uncontrolled pilot study","volume":"35","author":"Krysiak","year":"2021","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S1734-1140(10)70357-1","article-title":"Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide","volume":"62","author":"Labuzek","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.2174\/092986707780597943","article-title":"Molecular anatomy of the brain endothelial barrier: An overview of the distributional features","volume":"14","author":"Ueno","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1095\/biolreprod.110.087023","article-title":"Metformin decreases GnRH- and activin-induced gonadotropin secretion in rat pituitary cells: Potential involvement of adenosine 5\u2032 monophosphate-activated protein kinase (PRKA)","volume":"84","author":"Tosca","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/BOR.0b013e3280113d1a","article-title":"Autoimmune thyroid diseases","volume":"19","author":"Caturegli","year":"2007","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-3-642-30726-3_17","article-title":"Thyroid disorders","volume":"214","author":"Gessl","year":"2012","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s12020-012-9703-2","article-title":"The incidence and prevalence of thyroid autoimmunity","volume":"42","author":"McLeod","year":"2012","journal-title":"Endocrine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/MED.0000000000000500","article-title":"Thyroid disease and the metabolic syndrome","volume":"26","author":"Mehran","year":"2019","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1258\/mi.2011.011003","article-title":"Insulin resistance and management of the menopause: A clinical hypothesis in practice","volume":"17","author":"Whitcroft","year":"2011","journal-title":"Menopause Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000445173","article-title":"Growth hormone and insulin-like growth factor-1","volume":"47","author":"Nicholls","year":"2016","journal-title":"Front. Horm. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fendo.2019.00136","article-title":"FSH beyond fertility","volume":"10","author":"Lizneva","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41586-022-04463-0","article-title":"FSH blockade improves cognition in mice with Alzheimer\u2019s disease","volume":"603","author":"Xiong","year":"2022","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1385\/ENDO:29:2:257","article-title":"The role of gonadotropins in Alzheimer\u2019s disease: Potential neurodegenerative mechanisms","volume":"29","author":"Barron","year":"2006","journal-title":"Endocrine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jbspin.2018.08.002","article-title":"Bone disorders associated with diabetes mellitus and its treatments","volume":"86","author":"Cortet","year":"2019","journal-title":"Jt. Bone Spine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.irn.2020.02.010","article-title":"Antidiabetic drugs for Alzheimer\u2019s and Parkinson\u2019s diseases: Repurposing insulin, metformin, and thiazolidinediones","volume":"155","author":"Cardoso","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Erge, E., Kiziltunc, C., Balci, S.B., Atak Tel, B.M., Bilgin, S., Duman, T.T., and Aktas, G. (2023). A novel inflammatory marker for the diagnosis of Hashimoto\u2019s thyroiditis: Platelet-count-to-lymphocyte-count ratio. Diseases, 11.","DOI":"10.3390\/diseases11010015"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1055\/s-0035-1564073","article-title":"Different effects of metformin on the hypothalamic-pituitary-thyroid axis in bromocriptine- and cabergoline-treated patients with Hashimoto\u2019s thyroiditis and glucose metabolism abnormalities","volume":"123","author":"Krysiak","year":"2015","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1111\/jcpt.13233","article-title":"The impact of combination therapy with metformin and exogenous vitamin D on hypothalamic-pituitary-thyroid axis activity in women with autoimmune thyroiditis and high-normal thyrotropin levels","volume":"45","author":"Krysiak","year":"2020","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"622262","DOI":"10.3389\/fphar.2021.622262","article-title":"Metformin: A novel weapon against inflammation","volume":"12","author":"Bai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2174\/1871530315666150316124019","article-title":"Metformin and inflammation: Its potential beyond glucose-lowering effect","volume":"15","author":"Saisho","year":"2015","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature11862","article-title":"Metabolism of inflammation limited by AMPK and pseudo-starvation","volume":"493","author":"Hardie","year":"2013","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1038\/emm.2016.81","article-title":"Regulation and function of AMPK in physiology and diseases","volume":"48","author":"Jeon","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jim.2009.10.001","article-title":"Detection of AMP-activated protein kinase in human sera by immuno-isoelectric focusing","volume":"351","author":"Malvoisin","year":"2009","journal-title":"Immunol. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.tips.2022.04.007","article-title":"Hypothalamic AMPK as a possible target for energy balance-related diseases","volume":"43","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.brainres.2010.10.026","article-title":"Neurobiological mechanisms underlying GnRH pulse generation by the hypothalamus","volume":"1364","author":"Maeda","year":"2010","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1095\/biolreprod.106.050831","article-title":"Metformin-induced stimulation of adenosine 5\u2032 monophosphate-activated protein kinase (PRKA) impairs progesterone secretion in rat granulosa cells","volume":"75","author":"Tosca","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"691432","DOI":"10.3389\/fendo.2021.691432","article-title":"Challenges in measuring AMH in the clinical setting","volume":"12","author":"Li","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10549-010-0834-y","article-title":"Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMP-activated protein kinase","volume":"123","author":"Brown","year":"2010","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/0974-1208.147490","article-title":"Gonadotrophins: The future","volume":"7","author":"Patil","year":"2014","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","article-title":"Clinical pharmacokinetics of metformin","volume":"50","author":"Graham","year":"2011","journal-title":"Clin. Pharmacokinet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4103\/2230-8210.146874","article-title":"Assessment of insulin sensitivity\/resistance","volume":"19","author":"Gutch","year":"2015","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Diabetes Prevention Program Research Group. Reduction the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2007.03.006","article-title":"The GLUT4 glucose transporter","volume":"5","author":"Huang","year":"2007","journal-title":"Cell Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/en.2006-0692","article-title":"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression","volume":"148","author":"Jager","year":"2007","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1023\/A:1006865715292","article-title":"TNF-alpha and insulin resistance: Summary and future prospects","volume":"182","author":"Peraldi","year":"1998","journal-title":"Mol. Cell Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00384-015-2490-5","article-title":"Induction of GLUT4 by inhibiting IFN-\u03b3: A winning move to halt type 2 diabetes?","volume":"31","author":"Mormile","year":"2016","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1210\/jc.2010-2986","article-title":"The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto\u2019s thyroiditis","volume":"96","author":"Krysiak","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.bbi.2014.03.008","article-title":"Cognitive and affective dysfunctions in autoimmune thyroiditis","volume":"41","author":"Leyhe","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12020-018-1649-6","article-title":"Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement","volume":"62","author":"Djurovic","year":"2018","journal-title":"Endocrine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s11154-022-09778-x","article-title":"How does Hashimoto\u2019s thyroiditis affect bone metabolism?","volume":"24","author":"Wu","year":"2023","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_50","first-page":"696","article-title":"The association of subclinical insulin resistance with thyroid autoimmunity in euthyroid individuals","volume":"59","author":"Blaslov","year":"2020","journal-title":"Acta Clin. Croat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/cen.14424","article-title":"Increased risk of dementia in hypothyroidism: A Danish nationwide register-based study","volume":"94","author":"Thvilum","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_52","first-page":"51","article-title":"A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation","volume":"20","author":"Liontiris","year":"2017","journal-title":"Hell. J. Nucl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2549491","DOI":"10.1155\/2017\/2549491","article-title":"Treatment with myo-inositol and selenium ensures euthyroidism in patients with autoimmune thyroiditis","volume":"2017","author":"Nordio","year":"2017","journal-title":"Int. J. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1385\/BTER:108:1-3:001","article-title":"Selenium levels in blood of Upper Silesian population: Evidence of suboptimal selenium status in a significant percentage of the population","volume":"108","author":"Poprzecki","year":"2005","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_55","first-page":"156","article-title":"Polish council for control of iodine deficiency disorders. Work of the Polish council for control of iodine deficiency disorders, and the model of iodine prophylaxis in Poland","volume":"63","year":"2012","journal-title":"Endokrynol. Pol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/7\/922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:59:59Z","timestamp":1760126399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/7\/922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,24]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ph16070922"],"URL":"https:\/\/doi.org\/10.3390\/ph16070922","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,24]]}}}