{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:54:37Z","timestamp":1789934077688,"version":"4.0.1"},"reference-count":32,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for PCOS. Methods: Thirty-two female Wistar Albino rats were randomly assigned into four groups: control (I), PCOS (II), PCOS + metformin (III), and PCOS + Thymoquinone (IV). PCOS was induced using 1 mg\/kg\/day letrozole for 21 days, followed by treatment with either metformin (500 mg\/kg\/day) or thymoquinone (50 mg\/kg\/day) for 30 days. Metabolic (glucose, insulin, HOMA-IR, lipid profile), hormonal (estrone, estradiol, testosterone, androstenedione), and histopathological parameters were assessed. Results: PCOS induction resulted in significant metabolic, hormonal, and ovarian dysfunctions. Final body weight was significantly higher in PCOS (309.0 \u00b1 7.5 g) vs. control (275.3 \u00b1 8.2 g, p &lt; 0.001), but reduced by metformin (294.0 \u00b1 7.4 g, p &lt; 0.01) and thymoquinone (305.7 \u00b1 7.5 g, p &lt; 0.01). Glucose levels were significantly elevated in PCOS (341.8 \u00b1 16.8 mg\/dL) vs. control (260.0 \u00b1 15.8 mg\/dL, p &lt; 0.01), while metformin (290.2 \u00b1 19.7 mg\/dL, p &lt; 0.05) and thymoquinone (320.3 \u00b1 13.7 mg\/dL, p &lt; 0.05) reduced glucose levels. Insulin and HOMA-IR were significantly increased in PCOS (p &lt; 0.001), but reduced by both treatments (p &lt; 0.01). Lipid profile improvements were observed, with significant reductions in TG and LDL-C and increases in HDL-C in both treatment groups (p &lt; 0.05\u20130.01). PCOS induced hyperandrogenism, with increased testosterone and androstenedione (p &lt; 0.05), and a decreased E2\/E1 ratio (p &lt; 0.001), which were significantly improved by metformin and thymoquinone (p &lt; 0.01). Ovarian histopathology showed increased cystic and atretic follicles and reduced corpus luteum in PCOS (p &lt; 0.05\u20130.01), which were significantly improved by both treatments. Conclusions: TMQ exerts metabolic, hormonal, and ovarian protective effects comparable to metformin, supporting its potential as a natural therapeutic alternative for PCOS management. Given that metformin is already established as a first-line pharmacological therapy, our findings suggest that TMQ may provide a promising complementary or alternative approach. Further clinical studies are warranted to evaluate its safety and efficacy in human PCOS patients.<\/jats:p>","DOI":"10.3390\/jcm14186561","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T09:32:32Z","timestamp":1758187952000},"page":"6561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Thymoquinone Versus Metformin in Letrozole-Induced PCOS: Comparative Insights into Metabolic, Hormonal, and Ovarian Outcomes"],"prefix":"10.3390","volume":"14","author":[{"given":"Onder","family":"Ercan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sular Academy Hospital, 46000 Kahramanmara\u015f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6837-3477","authenticated-orcid":false,"given":"Recep","family":"Dokuyucu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Specialization Training Center (TUSMER), 06230 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ergun","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, 06010 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tumay","family":"Ozgur","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Mustafa Kemal University, 31040 Hatay, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-024-00511-3","article-title":"Polycystic ovary syndrome","volume":"10","author":"Teede","year":"2024","journal-title":"Nat. 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