{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T14:31:52Z","timestamp":1772721112939,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Low vitamin D status was found to attenuate the impact of metformin on circulating levels of anterior pituitary hormones, but this inhibitory effect was absent in vitamin D-repleted subjects. No previous study investigated the interaction between metformin and exogenous vitamin D at the pituitary levels in individuals with normal vitamin D status. Methods: Our pilot, single-center, prospective, matched-cohort study enrolled 59 postmenopausal women with subclinical hypothyroidism and 25-hydroxyvitamin D levels in the range between 75 and 150 nmol\/L. For the following six months, all the participants were treated with either metformin\/vitamin D combination therapy (group 1, n = 27) or metformin alone (group 2, n = 32). The outcomes of interest included 25-hydroxyvitamin D, fasting glucose, HOMA-IR, HbA1c, TSH, FSH, LH, prolactin, ACTH, free thyroid hormones, estradiol and IGF-1. A parallel study investigated the impact of vitamin D monotherapy on the outcome measures in insulin-resistant women meeting the remaining inclusion criteria. Results: No differences in baseline biomarker values were observed between groups 1 and 2. Ninety-three percent of the patients completed the study. The increase in 25-hydroxyvitamin D levels was observed exclusively in group 1. Although glucose homeostasis markers and post-treatment levels of TSH and FSH were lower at the end of the study than at baseline in both groups, the effect of treatment was more pronounced in group 1 than in group 2. Metformin\/vitamin D combination therapy, but not metformin alone, reduced LH and prolactin levels. In both groups, the TSH- and gonadotropin-lowering effects of metformin correlated with baseline levels of these pituitary hormones. Levels of ACTH, free thyroxine, free triiodothyronine, estradiol and IGF-1 remained stable throughout the study. The effects of vitamin D monotherapy were confined to an increase in plasma 25-hydroxyvitamin D concentrations and a modest enhancement in insulin sensitivity. Conclusions: Exogenous vitamin D potentiates the pituitary effects of metformin in postmenopausal women with subclinical hypothyroidism.<\/jats:p>","DOI":"10.3390\/nu18050838","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:11:22Z","timestamp":1772716282000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Exogenous Vitamin D on Pituitary Effects of Metformin in Postmenopausal Women with Subclinical Hypothyroidism and Normal Vitamin D Status: A Pilot Study"],"prefix":"10.3390","volume":"18","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, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-4563","authenticated-orcid":false,"given":"Karolina","family":"Kowalcze","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Academy of Silesia, Rolna 43, 40-555 Katowice, Poland"},{"name":"Department of Pediatrics in Bytom, Faculty of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-5262","authenticated-orcid":false,"given":"Johannes","family":"Ott","sequence":"additional","affiliation":[{"name":"Clinical Division of Gynecologic Endocrinology and Reproductive Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-7139","authenticated-orcid":false,"given":"Simona","family":"Zaami","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-4269","authenticated-orcid":false,"given":"Giuseppe","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-2906","authenticated-orcid":false,"given":"Bogus\u0142aw","family":"Okopie\u0144","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 9. 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