{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:45:08Z","timestamp":1787316308684,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Foundation for Dietetic Research","award":["512663"],"award-info":[{"award-number":["512663"]}]},{"name":"Canadian Foundation for Dietetic Research","award":["510543"],"award-info":[{"award-number":["510543"]}]},{"name":"Allen Foundation Inc.","award":["512663"],"award-info":[{"award-number":["512663"]}]},{"name":"Allen Foundation Inc.","award":["510543"],"award-info":[{"award-number":["510543"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Approximately 16% of North American couples are affected by infertility, with 30% of cases being attributable to male factor infertility. The regulation of reproductive hormones via the hypothalamic\u2013pituitary\u2013gonadal axis is important for spermatogenesis and subsequently male fertility. Maintaining iron homeostasis is critical to normal reproductive physiological function. This cross-sectional study\u2019s objective was to determine the association between serum biomarkers of iron and reproductive hormones. Men experiencing infertility (n = 303) were recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for iron and ferritin as biomarkers of iron status and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin), which were the primary outcome. Associations were determined using non-parametric Spearman\u2019s rank correlation coefficient, linear regressions, and logistic regressions. A significant independent monotonic inverse relationship between serum iron and prolactin (p = 0.0002) was found. In linear regression analyses, iron was inversely associated with luteinizing hormone (unadjusted p = 0.03, adjusted p = 0.03) and prolactin (unadjusted p = 0.001 and adjusted p = 0.003). Serum ferritin was inversely associated with both gonadotropins, follicle-stimulating hormone (adjusted p = 0.03), and luteinizing hormone (adjusted p = 0.02). These findings suggest that biomarkers of iron are associated with pituitary-produced reproductive hormones, which play a role in the hypothalamic\u2013pituitary\u2013gonadal signaling pathway involved in spermatogenesis, testicular testosterone production, and male fertility.<\/jats:p>","DOI":"10.3390\/nu16020290","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T03:50:56Z","timestamp":1705549856000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Biomarkers of Iron Are Associated with Anterior-Pituitary-Produced Reproductive Hormones in Men with Infertility"],"prefix":"10.3390","volume":"16","author":[{"given":"Matineh","family":"Rastegar Panah","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Medical Sciences Building, 5th Floor, Room 5326A, 1 King\u2019s College Circle, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Jarvi","sequence":"additional","affiliation":[{"name":"Murray Koffler Urologic Wellness Centre, Department of Urology, Mount Sinai Hospital, 60 Murray Street, 6th Floor, Toronto, ON M5T 3L, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Lo","sequence":"additional","affiliation":[{"name":"Murray Koffler Urologic Wellness Centre, Department of Urology, Mount Sinai Hospital, 60 Murray Street, 6th Floor, Toronto, ON M5T 3L, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8877-6414","authenticated-orcid":false,"given":"Ahmed","family":"El-Sohemy","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Medical Sciences Building, 5th Floor, Room 5326A, 1 King\u2019s College Circle, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","unstructured":"Public Health Agency of Canada (2020, January 13). \u201cFertility,\u201d aem. Available online: https:\/\/www.canada.ca\/en\/public-health\/services\/fertility\/fertility.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1210\/jc.2006-1375","article-title":"A Population-Level Decline in Serum Testosterone Levels in American Men","volume":"92","author":"Travison","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal trends in sperm count: A systematic review and meta-regression analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.euf.2020.02.006","article-title":"Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA","volume":"7","author":"Lokeshwar","year":"2021","journal-title":"Eur. Urol. Focus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0094-0143(02)00117-9","article-title":"Endocrine causes of male infertility","volume":"30","author":"Jarow","year":"2003","journal-title":"Urol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/00325481.1987.11699712","article-title":"Male infertility. 3. Endocrine causes","volume":"81","author":"McNally","year":"1987","journal-title":"Postgrad. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/01485010701271786","article-title":"Genetic risk factors in male infertility","volume":"53","author":"Krausz","year":"2007","journal-title":"Arch. Androl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.smrv.2018.07.006","article-title":"Linking sleep disturbance to idiopathic male infertility","volume":"42","author":"Palnitkar","year":"2018","journal-title":"Sleep Med. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3389\/fphys.2019.01356","article-title":"Relationship Between Smoking Habit and Sperm Parameters Among Patients Attending an Infertility Clinic","volume":"10","author":"Rehman","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1080\/10937400701873472","article-title":"Human exposure to endocrine disrupters and semen quality","volume":"11","author":"Phillips","year":"2008","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"490","DOI":"10.21037\/tau.2018.05.17","article-title":"Endocrine disrupting chemicals and impact on male reproductive health","volume":"7","author":"Rehman","year":"2018","journal-title":"Transl. Androl. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11934-018-0805-0","article-title":"The Role of Lifestyle in Male Infertility: Diet, Physical Activity, and Body Habitus","volume":"19","author":"Hayden","year":"2018","journal-title":"Curr. Urol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1530\/REP-17-0161","article-title":"Obesity, a serious etiologic factor for male subfertility in modern society","volume":"154","author":"Liu","year":"2017","journal-title":"Reproduction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/MOU.0000000000000417","article-title":"Obesity and male infertility","volume":"27","author":"Kahn","year":"2017","journal-title":"Curr. Opin. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"450","DOI":"10.4103\/1008-682X.148076","article-title":"Male obesity and subfertility, is it really about increased adiposity?","volume":"17","author":"McPherson","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1093\/humrep\/des311","article-title":"Intake of food groups and idiopathic asthenozoospermia: A case-control study","volume":"27","author":"Eslamian","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1093\/humrep\/des298","article-title":"Dietary patterns and semen quality in young men","volume":"27","author":"Gaskins","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1093\/humrep\/dep024","article-title":"Associations between dietary patterns and semen quality in men undergoing IVF\/ICSI treatment","volume":"24","author":"Vujkovic","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, C.-Y., Chou, Y.-C., Chao, J.C.-J., Hsu, C.-Y., Cha, T.-L., and Tsao, C.-W. (2015). The Association between Dietary Patterns and Semen Quality in a General Asian Population of 7282 Males. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134224"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.21037\/tau-20-592","article-title":"Nutrition, genetic variation and male fertility","volume":"10","author":"Vanderhout","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4103\/0974-1208.170370","article-title":"Trends of male factor infertility, an important cause of infertility: A review of literature","volume":"8","author":"Kumar","year":"2015","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S367","DOI":"10.21037\/tau.2018.03.25","article-title":"Update on male reproductive endocrinology","volume":"7","author":"Clavijo","year":"2018","journal-title":"Transl. Androl. Urol."},{"key":"ref_24","unstructured":"(2020, November 16). Hormones and Male Infertility|MetroVan Urology. Available online: https:\/\/www.metrovanurology.com\/hormones-and-male-infertility."},{"key":"ref_25","unstructured":"(2020, November 09). Male Sexual Response and Hormonal Control|SEER Training, Available online: https:\/\/training.seer.cancer.gov\/anatomy\/reproductive\/male\/response.html."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/physrev.00018.2016","article-title":"Estrogens in Male Physiology","volume":"97","author":"Cooke","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.4103\/1008-682X.173932","article-title":"The role of estradiol in male reproductive function","volume":"18","author":"Schulster","year":"2016","journal-title":"Asian J. Androl."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.aju.2017.10.002","article-title":"Hyperprolactinaemia in male infertility: Clinical case scenarios","volume":"16","author":"Dabbous","year":"2017","journal-title":"Arab. J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s11934-018-0808-x","article-title":"Iron and a Man\u2019s Reproductive Health: The Good, the Bad and the Ugly","volume":"19","author":"Gabrielsen","year":"2018","journal-title":"Curr. Urol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"568S","DOI":"10.1093\/jn\/131.2.568S","article-title":"Iron biology in immune function, muscle metabolism and neuronal functioning","volume":"131","author":"Beard","year":"2001","journal-title":"J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zeitoun, T., and El-Sohemy, A. (2023). Using Mendelian Randomization to Study the Role of Iron in Health and Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713458"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hales, K.G. (2010). Iron testes: Sperm mitochondria as a context for dissecting iron metabolism. BMC Biol., 8.","DOI":"10.1186\/1741-7007-8-79"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0098-2997(00)00006-6","article-title":"The roles of iron in health and disease","volume":"22","author":"Lieu","year":"2001","journal-title":"Mol. Aspects Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10815-014-0344-7","article-title":"Iron and copper in male reproduction: A double-edged sword","volume":"32","author":"Tvrda","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1365-2605.1987.tb00379.x","article-title":"Transport of transferrin-bound iron into rat Sertoli cells and spermatids","volume":"10","author":"Toebosch","year":"1987","journal-title":"Int. J. Androl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"503","DOI":"10.2527\/2003.812503x","article-title":"Relationships of testicular iron and ferritin concentrations with testicular weight and sperm production in boars","volume":"81","author":"Wise","year":"2003","journal-title":"J. Anim. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0002-9378(96)70325-3","article-title":"Increased levels of redox-active iron in follicular fluid: A possible cause of free radical-mediated infertility in beta-thalassemia major","volume":"174","author":"Reubinoff","year":"1996","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chao, K.-C., Chang, C.-C., Chiou, H.-Y., and Chang, J.-S. (2015). Serum Ferritin Is Inversely Correlated with Testosterone in Boys and Young Male Adolescents: A Cross-Sectional Study in Taiwan. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144238"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/geronj\/30.5.531","article-title":"The pathogenesis of hypophyseal fibrosis in aging: Its relationship to tissue iron deposition","volume":"30","author":"Greenberg","year":"1975","journal-title":"J. Gerontol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ajh.22247","article-title":"Pituitary iron and volume predict hypogonadism in transfusional iron overload","volume":"87","author":"Noetzli","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E190","DOI":"10.1002\/ajh.24083","article-title":"Fertility in transfusion-dependent thalassemia men: Effects of iron burden on the reproductive axis","volume":"90","author":"Singer","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_42","first-page":"295","article-title":"Pituitary siderosis. A histologic, immunocytologic, and ultrastructural study","volume":"93","author":"Bergeron","year":"1978","journal-title":"Am. J. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF02739976","article-title":"The Anterior Pituitary in Hemochromatosis","volume":"7","author":"Kontogeorgos","year":"1996","journal-title":"Endocr. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1046\/j.1365-2265.2000.00962.x","article-title":"Reversible hypogonadotrophic hypogonadism in sexually infantile male thalassaemic patients with transfusional iron overload","volume":"53","author":"Chatterjee","year":"2000","journal-title":"Clin. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/oxfordjournals.humrep.a019515","article-title":"Pituitary-testicular axis in men with beta-thalassaemia major","volume":"11","author":"Papadimas","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.bcp.2017.12.001","article-title":"Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages","volume":"148","author":"Dichtl","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","unstructured":"(2023, May 24). Prolactin and Dopamine: What Is the Connection? A Review Article\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/18477617\/."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mce.2017.06.019","article-title":"Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms","volume":"454","author":"Macchi","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1143579","DOI":"10.3389\/frph.2023.1143579","article-title":"Ascorbic acid is associated with favourable hormonal profiles among infertile males","volume":"5","author":"Tahir","year":"2023","journal-title":"Front. Reprod. Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1600-0609.2004.00371.x","article-title":"Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients","volume":"74","author":"Shalitin","year":"2005","journal-title":"Eur. J. Haematol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2147\/JBM.S232562","article-title":"The Effect of Serum Ferritin Level on Gonadal, Prolactin, Thyroid Hormones, and Thyroid Stimulating Hormone in Adult Males with Sickle Cell Anemia","volume":"11","author":"Mostafa","year":"2020","journal-title":"JBM"},{"key":"ref_52","unstructured":"(2021, February 16). The Association between the Levels of Serum Ferritin and Sex Hormones in a Large Scale of Chinese Male Population. Available online: https:\/\/journals.plos.org\/plosone\/article?id=10.1371\/journal.pone.0075908."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.tjnut.2023.03.012","article-title":"Population Iron Status in Canada: Results from the Canadian Health Measures Survey 2012\u20132019","volume":"153","author":"Cooper","year":"2023","journal-title":"J. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/2\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:49:32Z","timestamp":1760104172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/2\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,18]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["nu16020290"],"URL":"https:\/\/doi.org\/10.3390\/nu16020290","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,18]]}}}