{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:11Z","timestamp":1787026391366,"version":"build-2736575974"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Hypothyroidism, a common endocrine disorder, has a high incidence in women and increases with age. Levothyroxine (LT4) is the standard therapy; however, achieving clinical and biochemical euthyroidism is challenging. Therefore, developing an accurate model for predicting LT4 dosage is crucial. This retrospective study aimed to identify factors affecting the daily dose of LT4 and develop a model to estimate the dose of LT4 in hypothyroidism from a cohort of 1,864 patients through a comprehensive analysis of electronic medical records. Univariate analysis was conducted to explore the relationships between clinical and non-clinical variables, including weight, sex, age, body mass index, diastolic blood pressure, comorbidities, food effects, drug-drug interactions, liver function, serum albumin and TSH levels. Among the models tested, the Extra Trees Regressor (ETR) demonstrated the highest predictive accuracy, achieving an R\u00b2 of 87.37% and the lowest mean absolute error of 9.4 mcg (95% CI: 7.7\u201311.2) in the test set. Other ensemble models, including Random Forest and Gradient Boosting, also showed strong performance (R\u00b2 &amp;gt; 80%). Feature importance analysis highlighted BMI (0.516 \u00b1 0.015) as the most influential predictor, followed by comorbidities (0.120 \u00b1 0.010) and age (0.080 \u00b1 0.005). The findings underscore the potential of machine learning in refining LT4 dose estimation by incorporating diverse clinical factors beyond traditional weight-based approaches. The model provides a solid foundation for personalized LT4 dosing, which can enhance treatment precision and reduce the risk of under- or over-medication. Further validation in external cohorts is essential to confirm its clinical applicability.<\/jats:p>","DOI":"10.3389\/fendo.2025.1415206","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T01:14:12Z","timestamp":1741914852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Tran Thi","family":"Ngan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang Huong","family":"Tra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngo Thi Quynh","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang Van","family":"Dung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Van","family":"Khai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham Van","family":"Linh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Thu","family":"Phuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.680647","article-title":"Risk of all-cause mortality in levothyroxine-treated hypothyroid patients: A nationwide Korean cohort study","volume":"12","author":"Sohn","year":"2021","journal-title":"Front Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"101367","DOI":"10.1016\/j.beem.2019.101367","article-title":"Hashimotos\u2019 thyroiditis: Epidemiology, pathogenesis, clinic and therapy","volume":"33","author":"Ragusa","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1548832","article-title":"The pathogenesis of Hashimoto\u2019s thyroiditis: Further developments in our understanding","volume":"47","author":"Weetman","year":"2015","journal-title":"Hormone Metab Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01477-1","article-title":"An update on the pathogenesis of Hashimoto\u2019s thyroiditis","volume":"44","author":"Weetman","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2022.2071059","article-title":"Getting the levothyroxine (LT4) dose right for adults with hypothyroidism: opportunities and challenges in the use of modern LT4 preparations","volume":"38","author":"Gottwald-Hostalek","year":"2022","journal-title":"Curr Med Res Opinion"},{"key":"B6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s12325-019-01078-2","article-title":"Levothyroxine dose adjustment to optimise therapy throughout a patient\u2019s lifetime","volume":"36","author":"Duntas","year":"2019","journal-title":"Adv Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.clinthera.2017.01.005","article-title":"Factors affecting gastrointestinal absorption of levothyroxine: A review","volume":"39","author":"Skelin","year":"2017","journal-title":"Clin Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cen.2014.82.issue-1","article-title":"Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS)","volume":"82","author":"Irving S","year":"2015","journal-title":"Clin Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1901214","article-title":"Drug effects on the thyroid","volume":"381","author":"Burch","year":"2019","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-4-199408150-00002","article-title":"Decreased levothyroxine requirement in women with hypothyroidism during androgen therapy for breast cancer","volume":"121","author":"Arafah","year":"1994","journal-title":"Ann Intern Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.21.2822","article-title":"Effect of calcium carbonate on the absorption of levothyroxine","volume":"283","author":"Singh","year":"2000","journal-title":"JAMA"},{"key":"B12","article-title":"Goodman and Gilman\u2019s the pharmacological basis of therapeutics. Cocaine, Amphetamine and Related Psychostimulants","author":"Goodman","year":"1990"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1983.tb03211.x","article-title":"Dopaminergic modulation of tsh and its subunits: in vivo and in vitro studies","volume":"18","author":"Cooper","year":"1983","journal-title":"Clin Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/cen.2018.89.issue-3","article-title":"Preconception management of thyroid dysfunction","volume":"89","author":"Okosieme","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0457","article-title":"2017 Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum","volume":"27","author":"Alexander","year":"2017","journal-title":"Thyroid"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0609","article-title":"Thyroid laboratory testing and management in women on thyroid replacement before pregnancy and associated pregnancy outcomes","volume":"31","author":"Lemieux","year":"2021","journal-title":"Thyroid"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0028","article-title":"Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement","volume":"24","author":"Jonklaas","year":"2014","journal-title":"Thyroid"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)91192-0","article-title":"Aging and the thyroid. Decreased requirement for thyroid hormone in older hypothyroid patients","volume":"75","author":"Sawin","year":"1983","journal-title":"Am J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0314","article-title":"Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study","volume":"173","author":"Del Duca","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0380","article-title":"Stable isotope pharmacokinetic studies provide insight into effects of age, sex, and weight on levothyroxine metabolism","volume":"28","author":"Younis","year":"2018","journal-title":"Thyroid"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0029","article-title":"Levothyroxine replacement doses are affected by gender and weight, but not age","volume":"21","author":"Devdhar","year":"2011","journal-title":"Thyroid"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2021.501","article-title":"T4+T3 combination therapy: an unsolved problem of increasing magnitude and complexity","volume":"36","author":"Wiersinga","year":"2021","journal-title":"Endocrinol Metab (Seoul)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000340","article-title":"Liver injury induced by levothyroxine tablets in a patient with hypothyroidism","volume":"132","author":"Wu","year":"2019","journal-title":"Chin Med J (Engl)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.46.0086","article-title":"Liver injury induced by levothyroxine in a patient with primary hypothyroidism","volume":"46","author":"Kawakami","year":"2007","journal-title":"Intern Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1590\/2359-3997000000066","article-title":"Clinical and laboratory characteristics of patients with thyroid diseases with and without alanine aminotransferase levels above the upper tertile - Cross-sectional analytical study","volume":"60","author":"Silva Nde","year":"2016","journal-title":"Arch Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198703263161302","article-title":"Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans","volume":"316","author":"Fish","year":"1987","journal-title":"N Engl J Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/bjs.5157","article-title":"Optimization of thyroxine replacement therapy after total or near-total thyroidectomy for benign thyroid disease","volume":"93","author":"Olubowale","year":"2006","journal-title":"Br J Surg"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2012.12.002","article-title":"Using body mass index to predict optimal thyroid dosing after thyroidectomy","volume":"216","author":"Ojomo","year":"2013","journal-title":"J Am Coll Surg"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.77.2.8345037","article-title":"Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine","volume":"77","author":"Biondi","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311901","article-title":"Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons","volume":"331","author":"Sawin","year":"1994","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.81.12.8954028","article-title":"Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis","volume":"81","author":"Uzzan","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4158\/1934-2403-8.6.457","article-title":"American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism","volume":"6","author":"Baskin","year":"2002","journal-title":"Endocr Pract"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/105072503321086962","article-title":"Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease","volume":"13","author":"Baloch","year":"2003","journal-title":"Thyroid"},{"key":"B34","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1530\/EC-15-0056","article-title":"Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency","volume":"63","author":"Midgley","year":"2015","journal-title":"Endocr Connect"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2409","article-title":"The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis","volume":"99","author":"Garmendia Madariaga","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/20786204.2012.10874256","article-title":"Hypothyroidism: an update","volume":"54","author":"Gaitonde","year":"2012","journal-title":"South Afr Family Pract"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048.1681","article-title":"BMI helps to calculate the initial levothyroxine dose after total thyr oidectomy","volume":"5","author":"Correia","year":"2021","journal-title":"J Endocr Soc"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac150.1590","article-title":"ODP490 levothyroxine dosing based on BMI and different causes of hypot hyroidism","volume":"6","author":"Darquea","year":"2022","journal-title":"J Endocr Soc"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2023.1896","article-title":"Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppres sion after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer","volume":"39","author":"Ryu","year":"2024","journal-title":"Endocrinol Metab"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2015.10.005","article-title":"Prospective Intervention of a Novel Levothyroxine Dosing Protocol Base d on Body Mass Index after Thyroidectomy","volume":"222","author":"Elfenbein","year":"2016","journal-title":"J Am Coll Surge"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.06.013","article-title":"Hypothyroid symptoms fail to predict thyroid insufficiency in old people: A population-based case-control study","volume":"129","author":"Carl\u00e9","year":"2016","journal-title":"Am J Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0621","article-title":"The different requirement of L-T4 therapy in congenital athyreosis com pared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level","volume":"171","author":"Bagattini","year":"2014","journal-title":"Eur J Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040079","article-title":"Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism","volume":"351","author":"Alexander","year":"2004","journal-title":"N Engl J Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13044-023-00163-7","article-title":"Age-related variation in thyroid function \u2013 a narrative review highlig hting important implications for research and clinical practice","volume":"6","author":"Taylor","year":"2023","journal-title":"Thyroid Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1515\/jpem-2017-0513","article-title":"Does initial dosing of levothyroxine in infants with congenital hypoth yroidism lead to frequent dose adjustments secondary to iatrogenic hyp erthyroidism on follow-up","volume":"31","author":"Craven","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2018.04.097","article-title":"The optimal dosing scheme for levothyroxine after thyroidectomy: A comprehensive comparison and evaluation","volume":"165","author":"Zaborek","year":"2019","journal-title":"Surgery"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00233","article-title":"Ulcerative colitis as a novel cause of increased need for levothyroxine","volume":"10","author":"Virili","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0256","article-title":"The levothyroxine absorption test: A four-year experience (2015-2018) at the mayo clinic","volume":"29","author":"Gonzales","year":"2019","journal-title":"Thyroid"},{"key":"B49","article-title":"The influence of lactose intolerance and other gastro-intestinal tract disorders on L-thyroxine absorption","volume":"4","author":"Rucha\u0142a","year":"2012","journal-title":"Endokrynol Pol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.626371","article-title":"L-T4 therapy in enteric malabsorptive disorders","volume":"12","author":"Fallahi","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-021-09691-9","article-title":"Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults","volume":"23","author":"Caron","year":"2021","journal-title":"Rev Endocr Metab Disord"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1210\/js.2019-OR19-3","article-title":"OR19-3 utility of the levothyroxine absorption test: the mayo clinic experience","volume":"3","author":"Gonzales","year":"2019","journal-title":"J Endocr Soc"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00564","article-title":"IBD and bile acid absorption: focus on pre-clinical and clinical observations","volume":"12","author":"Fitzpatrick","year":"2020","journal-title":"Front. Physiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.29252\/ijrm.14.11.677","article-title":"Thyroid hormone dysfunction during pregnancy: A review","volume":"14","author":"Alemu","year":"2016","journal-title":"IJRM"},{"key":"B55","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1093\/humupd\/dmu028","article-title":"Molecular basis of thyrotropin and thyroid hormone action during impla ntation and early development","volume":"20","author":"Colicchia","year":"2014","journal-title":"Hum Reprod Update"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2012.692001","article-title":"Thyroid disorders during pregnancy","volume":"28","author":"Parkes","year":"2012","journal-title":"Gynecol Endocrinol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0151","article-title":"Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF","volume":"173","author":"Busnelli","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1507\/endocrj.EJ14-0083","article-title":"Screening and management of hypothyroidism in pregnancy: results of an Asian survey","volume":"61","author":"Azizi","year":"2014","journal-title":"Endocr J"},{"key":"B59","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1530\/EJE-11-0729","article-title":"Treatment and screening of hypothyroidism in pregnancy: results of a European survey","volume":"166","author":"Vaidya","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1412-4","article-title":"Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care","volume":"59","author":"Guglielmi","year":"2018","journal-title":"Endocrine"},{"key":"B61","doi-asserted-by":"publisher","first-page":"100189","DOI":"10.1016\/j.jcte.2019.100189","article-title":"A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences","volume":"16","author":"Benvenga","year":"2019","journal-title":"J Clin Transl Endocrinol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0014","article-title":"Ciprofloxacin and rifampin have opposite effects on levothyroxine absorption","volume":"23","author":"Goldberg","year":"2013","journal-title":"Thyroid"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2014.926161","article-title":"Effects of zinc and selenium supplementation on thyroid function in overweight and obese hypothyroid female patients: A randomized double-blind controlled trial","volume":"34","author":"Mahmoodianfard","year":"2015","journal-title":"J Am Coll Nutr"},{"key":"B64","article-title":"Metabolism of thyroid hormone","volume-title":"Endotext","author":"Peeters","year":"2000"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.5.H1627","article-title":"Interstitial fluid pressure, composition of interstitium, and interstitial exclusion of albumin in hypothyroid rats","volume":"278","author":"Wiig","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2022.11.025","article-title":"Efficacy of machine learning to identify clinical factors influencing levothyroxine dosage after total thyroidectomy","volume":"225","author":"Zheng","year":"2023","journal-title":"Am J Surge"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1055\/a-1336-3502","article-title":"Development and prospective validation of the levothyroxine dose prediction model in primary hypothyroidism","volume":"53","author":"Singh","year":"2021","journal-title":"Hormone Metab Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1425101","article-title":"A predictive model for L-T4 dose in postoperative DTC after RAI therap y and its clinical validation in two institutions","volume":"15","author":"Liu","year":"2024","journal-title":"Front Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1415206\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T01:14:15Z","timestamp":1741914855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1415206\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":68,"alternative-id":["10.3389\/fendo.2025.1415206"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1415206","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"article-number":"1415206"}}