{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:12:41Z","timestamp":1793931161801,"version":"4.8.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Pharm Health Care Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. Crocin is known as the main component of saffron, which has antioxidant properties and has the ability to scavenge free radicals. Considering the pathophysiology of PCOS and also the anti-inflammatory and antioxidant properties of crocin in improving insulin resistance, we aimed to evaluate the efficacy of the combination of crocin and metformin compared to metformin alone in PCOS patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study is a prospective, double-blind randomized controlled clinical trial. Fifty patients with PCOS and hirsutism were included from Baqaipour Obstetrics and Gynecology Clinic in Yazd and randomly assigned into the two study arms of control group [metformin and placebo (<jats:italic>n<\/jats:italic>\u2009=\u200925)] or intervention group [metformin and crocin (<jats:italic>n<\/jats:italic>\u2009=\u200925)]. Patients were administered crocin 15\u00a0mg tablets once a day in combination with metformin 500\u00a0mg twice a day for 12 weeks to complete three full periods of the monthly cycle. The studied endpoints were evaluated at the beginning and end of the study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Crocin significantly improved the serum level of follicle-stimulating hormone (FSH) (<jats:italic>P<\/jats:italic>\u2009=\u20090.048) and Ferriman- Gallwey score (<jats:italic>P<\/jats:italic>\u2009=\u20090.042) at day 90. Furthermore, crocin group had a significant improvement in terms of acne severity at the end of the study (<jats:italic>P<\/jats:italic>\u2009=\u20090.03), so that none of the patients in the crocin group had severe acne at the end of the study. However, the comparisons between two groups were not statistically significant for other evaluated outcomes including fasting blood sugar (FBS), dihydroepiandrosterone-sulfate (DHEA-S), luteinizing hormone (LH), dermatology life quality index (DLQI), and blood pressure (BP) at the end of the study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In the present study, concurrent use of crocin along with metformin was significantly effective in ameliorating the unpleasant side effects of PCOS, including hirsutism and acne, and increasing FSH sex hormone levels in patients with PCOS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registry date<\/jats:title>\n            <jats:p>26\/08\/2021, <jats:bold>Trial Registry number<\/jats:bold>: IRCT20210730052027N1.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40780-025-00432-7","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T08:47:59Z","timestamp":1754642879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of therapeutic effects of Crocin in patients with polycystic ovary syndrome: A randomized Double-Blind clinical trial"],"prefix":"10.1186","volume":"11","author":[{"given":"Fatemeh","family":"Saghafi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atiyeh","family":"Javaheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Mohammadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nooshin","family":"Hatamizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Khanizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdieh","family":"Safakish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-1641","authenticated-orcid":false,"given":"Adeleh","family":"Sahebnasagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"432_CR1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.biopha.2018.08.135","volume":"107","author":"Q Hu","year":"2018","unstructured":"Hu Q, Jin J, Zhou H, Yu D, Qian W, Zhong Y, et al. Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising Kisspeptin neurons. Biomed Pharmacother. 2018;107:1363\u20139.","journal-title":"Biomed Pharmacother"},{"issue":"8","key":"432_CR2","first-page":"Cd005552","volume":"8","author":"E Fraison","year":"2020","unstructured":"Fraison E, Kostova E, Moran LJ, Bilal S, Ee CC, Venetis C, et al. Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome. Cochrane Database Syst Rev. 2020;8(8):Cd005552.","journal-title":"Cochrane Database Syst Rev"},{"key":"432_CR3","doi-asserted-by":"crossref","unstructured":"Zhuang S, Jing C, Yu L, Ji L, Liu W, Hu X. The relationship between polycystic ovary syndrome and infertility: a bibliometric analysis. Annals Translational Med. 2022;10(6).","DOI":"10.21037\/atm-22-714"},{"key":"432_CR4","doi-asserted-by":"crossref","unstructured":"Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J women\u2019s health. 2015:745\u201363.","DOI":"10.2147\/IJWH.S70314"},{"issue":"4","key":"432_CR5","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1111\/jcmm.16205","volume":"25","author":"W Ye","year":"2021","unstructured":"Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25(4):1825\u201337.","journal-title":"J Cell Mol Med"},{"issue":"3","key":"432_CR6","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/humrep\/des463","volume":"28","author":"NK Stepto","year":"2013","unstructured":"Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic\u2013hyperinsulaemic clamp. Hum Reprod. 2013;28(3):777\u201384.","journal-title":"Hum Reprod"},{"issue":"1","key":"432_CR7","doi-asserted-by":"publisher","first-page":"e12487","DOI":"10.1002\/rmb2.12487","volume":"21","author":"M Harada","year":"2022","unstructured":"Harada M. Pathophysiology of polycystic ovary syndrome revisited: current Understanding and perspectives regarding future research. Reproductive Med Biology. 2022;21(1):e12487.","journal-title":"Reproductive Med Biology"},{"key":"432_CR8","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.diabres.2017.06.011","volume":"130","author":"D Macut","year":"2017","unstructured":"Macut D, Bjeki\u0107-Macut J, Raheli\u0107 D, Dokni\u0107 M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract. 2017;130:163\u201370.","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"432_CR9","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/ijcp.12787","volume":"70","author":"SK Graff","year":"2016","unstructured":"Graff SK, Mario FM, Ziegelmann P, Spritzer PM. Effects of Orlistat vs. metformin on weight loss-related clinical variables in women with PCOS: systematic review and meta-analysis. Int J Clin Pract. 2016;70(6):450\u201361.","journal-title":"Int J Clin Pract"},{"issue":"10","key":"432_CR10","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1093\/humrep\/des262","volume":"27","author":"AM Fulghesu","year":"2012","unstructured":"Fulghesu AM, Romualdi D, Di Florio C, Sanna S, Tagliaferri V, Gambineri A, et al. Is there a dose-response relationship of Metformin treatment in patients with polycystic ovary syndrome? Results from a multicentric study. Hum Reprod. 2012;27(10):3057\u201366.","journal-title":"Hum Reprod"},{"key":"432_CR11","unstructured":"Vakili A, Eianali MR, Bandegi AR. The protective effects of saffron against the oxidative damage in a transient model of focal cerebral ischemia in rats. Tehran Univ Med J. 2011:405\u201312."},{"issue":"16","key":"432_CR12","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1080\/10408398.2013.879467","volume":"56","author":"G Broadhead","year":"2016","unstructured":"Broadhead G, Chang A, Grigg J, McCluskey P. Efficacy and safety of saffron supplementation: current clinical findings. Crit Rev Food Sci Nutr. 2016;56(16):2767\u201376.","journal-title":"Crit Rev Food Sci Nutr"},{"key":"432_CR13","doi-asserted-by":"publisher","first-page":"111521","DOI":"10.1016\/j.fct.2020.111521","volume":"143","author":"M Hashemzaei","year":"2020","unstructured":"Hashemzaei M, Mamoulakis C, Tsarouhas K, Georgiadis G, Lazopoulos G, Tsatsakis A, et al. Crocin: A fighter against inflammation and pain. Food Chem Toxicol. 2020;143:111521.","journal-title":"Food Chem Toxicol"},{"issue":"4","key":"432_CR14","first-page":"334","volume":"22","author":"M Zeinali","year":"2019","unstructured":"Zeinali M, Zirak MR, Rezaee SA, Karimi G, Hosseinzadeh H. Immunoregulatory and anti-inflammatory properties of crocus sativus (Saffron) and its main active constituents: A review. Iran J Basic Med Sci. 2019;22(4):334.","journal-title":"Iran J Basic Med Sci"},{"issue":"1","key":"432_CR15","doi-asserted-by":"publisher","first-page":"8841726","DOI":"10.1155\/2021\/8841726","volume":"2021","author":"MA Hussain","year":"2021","unstructured":"Hussain MA, Abogresha NM, AbdelKader G, Hassan R, Abdelaziz EZ, Greish SM. Antioxidant and anti-inflammatory effects of Crocin ameliorate doxorubicin\u2010induced nephrotoxicity in rats. Oxidative Med Cell Longev. 2021;2021(1):8841726.","journal-title":"Oxidative Med Cell Longev"},{"issue":"2","key":"432_CR16","first-page":"956","volume":"43","author":"C Wang","year":"2019","unstructured":"Wang C, Cai X, Hu W, Li Z, Kong F, Chen X, et al. Investigation of the neuroprotective effects of Crocin via antioxidant activities in HT22 cells and in mice with Alzheimer\u2019s disease. Int J Mol Med. 2019;43(2):956\u201366.","journal-title":"Int J Mol Med"},{"issue":"5","key":"432_CR17","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1080\/09168451.2016.1263145","volume":"81","author":"X Li","year":"2017","unstructured":"Li X, Jiang C, Zhu W. Crocin reduces the inflammation response in rheumatoid arthritis. Biosci Biotechnol Biochem. 2017;81(5):891\u20138.","journal-title":"Biosci Biotechnol Biochem"},{"key":"432_CR18","doi-asserted-by":"crossref","unstructured":"Colapietro A, Mancini A, D\u2019Alessandro AM, Festuccia C. Crocetin and Crocin from saffron in cancer chemotherapy and chemoprevention. Anti-Cancer agents in medicinal chemistry (Formerly current medicinal chemistry-Anti-Cancer agents). 2019;19(1):38\u201347.","DOI":"10.2174\/1871520619666181231112453"},{"issue":"7","key":"432_CR19","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/ptr.4836","volume":"27","author":"S Shirali","year":"2013","unstructured":"Shirali S, Zahra Bathaie S, Nakhjavani M. Effect of Crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res. 2013;27(7):1042\u20137.","journal-title":"Phytother Res"},{"key":"432_CR20","doi-asserted-by":"publisher","first-page":"103238","DOI":"10.1016\/j.etap.2019.103238","volume":"72","author":"MM Samaha","year":"2019","unstructured":"Samaha MM, Said E, Salem HA. A comparative study of the role of Crocin and sitagliptin in Attenuation of STZ-induced diabetes mellitus and the associated inflammatory and apoptotic changes in pancreatic \u03b2-islets. Environ Toxicol Pharmacol. 2019;72:103238.","journal-title":"Environ Toxicol Pharmacol"},{"issue":"4","key":"432_CR21","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1016\/j.foodchem.2012.06.092","volume":"135","author":"C Kang","year":"2012","unstructured":"Kang C, Lee H, Jung E-S, Seyedian R, Jo M, Kim J, et al. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms. Food Chem. 2012;135(4):2350\u20138.","journal-title":"Food Chem"},{"issue":"1","key":"432_CR22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jnutbio.2006.03.010","volume":"18","author":"L Xi","year":"2007","unstructured":"Xi L, Qian Z, Xu G, Zheng S, Sun S, Wen N, et al. Beneficial impact of Crocetin, a carotenoid from Saffron, on insulin sensitivity in fructose-fed rats. J Nutr Biochem. 2007;18(1):64\u201372.","journal-title":"J Nutr Biochem"},{"issue":"2","key":"432_CR23","first-page":"198","volume":"17","author":"S Sadoughi","year":"2017","unstructured":"Sadoughi S. Effects of Crocin on ovarian follicle and serum sex hormone in letrozole-induced polycystic ovarian syndrome in rat model. J Ardabil Univ Med Sci. 2017;17(2):198\u2013210.","journal-title":"J Ardabil Univ Med Sci"},{"issue":"1","key":"432_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13098-020-00568-6","volume":"12","author":"V Behrouz","year":"2020","unstructured":"Behrouz V, Dastkhosh A, Hedayati M, Sedaghat M, Sharafkhah M, Sohrab G. The effect of Crocin supplementation on glycemic control, insulin resistance and active AMPK levels in patients with type 2 diabetes: a pilot study. Diabetol Metab Syndr. 2020;12(1):1\u20139.","journal-title":"Diabetol Metab Syndr"},{"key":"432_CR25","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.jff.2014.03.017","volume":"8","author":"M Mashmoul","year":"2014","unstructured":"Mashmoul M, Azlan A, Yusof BNM, Khaza\u2019ai H, Mohtarrudin N, Boroushaki MT. Effects of saffron extract and Crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. J Funct Foods. 2014;8:180\u20137.","journal-title":"J Funct Foods"},{"issue":"December","key":"432_CR26","first-page":"5237","volume":"87","author":"MN ELHAM","year":"2019","unstructured":"ELHAM MN, YASMIN M. Effect of Crocin on Letrozole-Induced polycystic ovarian syndrome. Med J Cairo Univ. 2019;87(December):5237\u201343.","journal-title":"Med J Cairo Univ"},{"key":"432_CR27","doi-asserted-by":"crossref","unstructured":"Moshfegh F, Balanejad SZ, Shahrokhabady K, Attaranzadeh A. Investigating the effect of crocus sativus (Saffron) petal Hydro-alcoholic extract on ovarian follicle, inflammatory markers, and antioxidant enzymes in mice model of polycystic ovary syndrome. Journal of Reproduction & Infertility; 2022.","DOI":"10.18502\/jri.v23i1.8447"},{"issue":"1","key":"432_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2288-4-26","volume":"4","author":"M Saghaei","year":"2004","unstructured":"Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Methodol. 2004;4(1):1\u20136.","journal-title":"BMC Med Res Methodol"},{"issue":"7","key":"432_CR29","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/S1701-2163(16)32202-2","volume":"28","author":"KE Liu","year":"2006","unstructured":"Liu KE, Tataryn IV, Sagle M. Use of Metformin for ovulation induction in women who have polycystic ovary syndrome with or without evidence of insulin resistance. J Obstet Gynecol Can. 2006;28(7):595\u20139.","journal-title":"J Obstet Gynecol Can"},{"key":"432_CR30","doi-asserted-by":"crossref","unstructured":"Sohrevardi SM, Heydari B, Azarpazhooh MR, Teymourzadeh M, Simental-Mend\u00eda LE, Atkin SL, et al. Therapeutic effect of Curcumin in women with polycystic ovary syndrome receiving metformin: a randomized controlled trial. Pharmacol Prop Plant-Derived Nat Prod Implications Hum Health. 2021;109:17.","DOI":"10.1007\/978-3-030-64872-5_9"},{"issue":"5","key":"432_CR31","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1016\/j.fertnstert.2008.02.101","volume":"91","author":"K Brennan","year":"2009","unstructured":"Brennan K, Huang A, Azziz R. Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril. 2009;91(5):1848\u201352.","journal-title":"Fertil Steril"},{"issue":"4","key":"432_CR32","first-page":"001","volume":"10","author":"P Yann","year":"2021","unstructured":"Yann P, Marion S. Comparison between calculated bioavailable testosterone level with radio-immunoassay result. J Biol. 2021;10(4):001\u20135.","journal-title":"J Biol"},{"issue":"6","key":"432_CR33","doi-asserted-by":"publisher","first-page":"631","DOI":"10.5114\/ada.2018.77615","volume":"35","author":"BG Lumezi","year":"2018","unstructured":"Lumezi BG, Berisha VL, Pupovci HL, Go\u00e7i A, Hajrushi AB. Grading of hirsutism based on the Ferriman-Gallwey scoring system in Kosovar women. Adv Dermatology Allergology\/Post\u0119py Dermatologii I Alergologii. 2018;35(6):631\u20135.","journal-title":"Adv Dermatology Allergology\/Post\u0119py Dermatologii I Alergologii"},{"key":"432_CR34","doi-asserted-by":"crossref","unstructured":"Vasileva M, Boskovski Briskoska V, Majhosheva M, Vasileva S, Vasilev S, Drakalska E. Quality of life in patients with psoriasis vulgaris uality of life in patients with psoriasis vulgaris during the COVID-19 pandemic. Our Dermatology Online J. 2020.","DOI":"10.7241\/ourd.2020S2.1"},{"issue":"7","key":"432_CR35","doi-asserted-by":"publisher","first-page":"505","DOI":"10.3109\/09513590.2014.895983","volume":"30","author":"AY Shahin","year":"2014","unstructured":"Shahin AY, Mohammed SA. Adding the phytoestrogen cimicifugae racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates\u2013a randomized trial. Gynecol Endocrinol. 2014;30(7):505\u201310.","journal-title":"Gynecol Endocrinol"},{"issue":"5","key":"432_CR36","first-page":"77","volume":"21","author":"F Rooshenas","year":"2018","unstructured":"Rooshenas F, Ashrafi M, Nazifi S, Aminlari M, Talebanzadeh S. Evaluation the effect of saffron aqueous extract on oxidative stress parameters and important biochemical enzymes of liver tissue in Streptozotocin-Induced diabetic rats. J Arak Univ Med Sci. 2018;21(5):77\u201387.","journal-title":"J Arak Univ Med Sci"},{"issue":"6","key":"432_CR37","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1002\/ptr.7474","volume":"36","author":"G Rahimi","year":"2022","unstructured":"Rahimi G, Shams S, Aslani MR. Effects of Crocin supplementation on inflammatory markers, lipid profiles, insulin and cardioprotective indices in women with PCOS: A randomized, double-blind, placebo-controlled trial. Phytother Res. 2022;36(6):2605\u201315.","journal-title":"Phytother Res"},{"issue":"3","key":"432_CR38","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.3390\/ijms23031264","volume":"23","author":"R Herman","year":"2022","unstructured":"Herman R, Kravos NA, Jensterle M, Jane\u017e A, Dol\u017ean V. Metformin and insulin resistance: a review of the underlying mechanisms behind changes in GLUT4-mediated glucose transport. Int J Mol Sci. 2022;23(3):1264.","journal-title":"Int J Mol Sci"},{"key":"432_CR39","unstructured":"Johnson NP. Metformin use in women with polycystic ovary syndrome. Annals Translational Med. 2014;2(6)."},{"issue":"8","key":"432_CR40","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1002\/ptr.5638","volume":"30","author":"S Samarghandian","year":"2016","unstructured":"Samarghandian S, Azimi-Nezhad M, Borji A, Farkhondeh T. Effect of Crocin on aged rat kidney through Inhibition of oxidative stress and Proinflammatory state. Phytother Res. 2016;30(8):1345\u201353.","journal-title":"Phytother Res"},{"key":"432_CR41","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.biopha.2017.12.077","volume":"98","author":"H Yaribeygi","year":"2018","unstructured":"Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333\u20137.","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"432_CR42","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.jssas.2018.03.007","volume":"18","author":"SM Jadouali","year":"2019","unstructured":"Jadouali SM, Atifi H, Mamouni R, Majourhat K, Bouzouba\u00e2 Z, Laknifli A, et al. Chemical characterization and antioxidant compounds of flower parts of Moroccan crocus sativus L. J Saudi Soc Agricultural Sci. 2019;18(4):476\u201380.","journal-title":"J Saudi Soc Agricultural Sci"},{"key":"432_CR43","doi-asserted-by":"publisher","first-page":"395","DOI":"10.12659\/MSM.912341","volume":"25","author":"Y Hong","year":"2019","unstructured":"Hong Y, Yin Y, Tan Y, Hong K, Zhou H. The Flavanone, naringenin, modifies antioxidant and steroidogenic enzyme activity in a rat model of Letrozole-Induced polycystic ovary syndrome. Med Sci Monit. 2019;25:395\u2013401.","journal-title":"Med Sci Monit"},{"key":"432_CR44","doi-asserted-by":"publisher","first-page":"113297","DOI":"10.1016\/j.biopha.2022.113297","volume":"153","author":"S Bastani","year":"2022","unstructured":"Bastani S, Vahedian V, Rashidi M, Mir A, Mirzaei S, Alipourfard I, et al. An evaluation on potential anti-oxidant and anti-inflammatory effects of Crocin. Biomed Pharmacother. 2022;153:113297.","journal-title":"Biomed Pharmacother"},{"key":"432_CR45","unstructured":"MOSHFEGH F, ZAFAR BS, SHAHROKHABADI K. ATTARANZADEH A. Evaluation of anti-inflammatory and antioxidant effects of hydroalcoholic extract of saffron petals on polycystic ovary syndrome in mice."},{"issue":"5","key":"432_CR46","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1080\/09513590.2020.1859474","volume":"37","author":"F Ramezani Tehrani","year":"2021","unstructured":"Ramezani Tehrani F, Behboudi-Gandevani S, Bidhendi Yarandi R, Saei Ghare Naz M, Carmina E. Prevalence of acne vulgaris among women with polycystic ovary syndrome: a systemic review and meta-analysis. Gynecol Endocrinol. 2021;37(5):392\u2013405.","journal-title":"Gynecol Endocrinol"},{"issue":"2","key":"432_CR47","first-page":"38","volume":"18","author":"J Qar","year":"2022","unstructured":"Qar J, Al-Trad B, Al Zoubi MS, Fayyad D, Aljabali AA, Omari S, et al. Crocin treatment improves testosterone induced benign prostatic hyperplasia in rats. J Men\u2019s Health. 2022;18(2):38.","journal-title":"J Men\u2019s Health"},{"issue":"1","key":"432_CR48","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1016\/j.ijwd.2017.02.007","volume":"3","author":"J Mihailidis","year":"2017","unstructured":"Mihailidis J, Dermesropian R, Taxel P, Luthra P, Grant-Kels JM. Endocrine evaluation of hirsutism. Int J Women\u2019s Dermatology. 2017;3(1):S6\u201310.","journal-title":"Int J Women\u2019s Dermatology"},{"key":"432_CR49","unstructured":"Fatemeh T, Zahra S, Mahboobe B, Elham A. G. Assessment of crocin toxicity on the rat liver. 2014."}],"container-title":["Journal of Pharmaceutical Health Care and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00432-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40780-025-00432-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00432-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T19:14:07Z","timestamp":1757358847000},"score":1,"resource":{"primary":{"URL":"https:\/\/jphcs.biomedcentral.com\/articles\/10.1186\/s40780-025-00432-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["432"],"URL":"https:\/\/doi.org\/10.1186\/s40780-025-00432-7","relation":{},"ISSN":["2055-0294"],"issn-type":[{"value":"2055-0294","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"assertion":[{"value":"1 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Study protocols were approved by the local Ethics Committee of Shahid Sadoughi University of Medical Sciences (Ethics ID: IR.SSU.MEDICINE.REC.1399.220). Following a health-screening questionnaire, all volunteers provided a written informed consent. Before the intervention, study protocol, benefits, and possible side effects were described for patients. Understandable written informed consent was obtained for all patients prior to participation in the study. This trial was performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent for publication was agreed upon in the written consent forms signed by all subjects for publication of identifying information\/images in a publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests regarding the publication of this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"69"}}