{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:13:34Z","timestamp":1790864014135,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Junior Project Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["12\/22"],"award-info":[{"award-number":["12\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg\/kg, 15 mg\/kg, and 45 mg\/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.<\/jats:p>","DOI":"10.3390\/pathophysiology31040041","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:54:09Z","timestamp":1728546849000},"page":"559-582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model"],"prefix":"10.3390","volume":"31","author":[{"given":"Dejana","family":"Rakic","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-8376","authenticated-orcid":false,"given":"Vladimir","family":"Jakovljevic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Human Pathology, I.M. Sechenov First Moscow State Medical University, 119146 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacology, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Jakovljevic Uzelac","sequence":"additional","affiliation":[{"name":"Institute of Medical Physiology \u201cRichard Burian\u201d, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Jovic","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Muric","sequence":"additional","affiliation":[{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7603-5865","authenticated-orcid":false,"given":"Bozidar","family":"Pindovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Dimitrijevic","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Arsenijevic","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovan","family":"Rakic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodanka","family":"Mitrovic","sequence":"additional","affiliation":[{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"},{"name":"Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Vulovic","sequence":"additional","affiliation":[{"name":"University Clinical Center Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"},{"name":"Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-0626","authenticated-orcid":false,"given":"Jovana","family":"Joksimovic Jovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1007\/s10815-022-02625-7","article-title":"A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS)","volume":"39","author":"Siddiqui","year":"2022","journal-title":"J. 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