{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:39:40Z","timestamp":1781285980558,"version":"3.54.1"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Programs of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404278"],"award-info":[{"award-number":["82404278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Programs of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404365"],"award-info":[{"award-number":["82404365"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0513200"],"award-info":[{"award-number":["2023ZD0513200"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M730317"],"award-info":[{"award-number":["2023M730317"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023T160066"],"award-info":[{"award-number":["2023T160066"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["3332023042"],"award-info":[{"award-number":["3332023042"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Project of Hebei Key Laboratory of Environment and Human Health","award":["202301"],"award-info":[{"award-number":["202301"]}]},{"name":"Open Project of Hebei Key Laboratory of Environment and Human Health","award":["202303"],"award-info":[{"award-number":["202303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The effect of heavy metals on male hormonal regulation\u2014particularly the hypothalamic\u2013pituitary\u2013testicular (HPT) axis\u2014remains poorly characterized. We aim to investigate associations between heavy metal exposure and HPT axis-related hormones. We analyzed data, including male participants aged 3\u201380 years, from a nationally representative survey. Five metals and twelve sex hormones were measured. We used multivariate linear regression and restricted cubic splines to assess associations and dose\u2013response relationships. Mixture effects were quantified using quantile-based g computation. The modifying effects of vitamin D and folate were examined. The underlying mechanisms were explored through a narrative review and integrative bioinformatics analysis. A total of 6547 males were included. Metal exposure was predominantly associated with hormonal perturbations in adolescents and older adults. Specifically, metal mixture was associated with hormones in adolescent males [effect range: \u22125.10% (95% CI: \u22129.24, \u22120.76) to 18.12% (95% CI: 9.80, 27.07)] and older males [effect range: 3.17% (95% CI: 0.07, 6.37) to 10.94% (95% CI: 4.82, 17.43)]. Effect modifications were observed for vitamin D in children and adolescents, and for folate across all age groups. The PI3K-Akt signaling pathway was identified as a potential mechanism. Our findings provide novel insights into the association and potential pathway between heavy metals and male hormonal disturbance.<\/jats:p>","DOI":"10.3390\/toxics14010055","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:43Z","timestamp":1767786403000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Dependent Effects of Heavy Metals on the Hypothalamic\u2013Pituitary\u2013Testicular Axis-Related Hormones in Men"],"prefix":"10.3390","volume":"14","author":[{"given":"Yayuan","family":"Mei","sequence":"first","affiliation":[{"name":"Big Data Center, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing 100045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfu","family":"Yan","sequence":"additional","affiliation":[{"name":"Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglan","family":"Ke","sequence":"additional","affiliation":[{"name":"Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihui","family":"Su","sequence":"additional","affiliation":[{"name":"Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangjia","family":"Luo","sequence":"additional","affiliation":[{"name":"Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobao","family":"Chen","sequence":"additional","affiliation":[{"name":"Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Big Data Center, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing 100045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Su","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, China"},{"name":"Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jinorgbio.2019.03.013","article-title":"The essential metals for humans: A brief overview","volume":"195","author":"Zoroddu","year":"2019","journal-title":"J. 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