{
  "abstract": "Hashimoto’s thyroiditis (HT) is markedly female predominant, but evidence for the mechanisms underlying this pattern is heterogeneous. This narrative review examines epidemiology, the clinicopathological spectrum, X-chromosome regulation, sex hormones, thyroid-local T- and B-cell responses, and environmental and life-course modifiers. To prevent disease association from being conflated with an explanation of sex bias, we distinguish (1) human HT studies reporting an explicit sex comparison (2), human HT studies without sex-stratified mechanistic analyses, and (3) non-HT human or experimental evidence used to generate hypotheses. Skewed X-chromosome inactivation has been investigated in female HT case–control studies, whereas sex-dependent downstream TLR7, CD40L and FOXP3 effects within human HT remain incompletely established. Estradiol has potentially opposing actions across immune subsets, progesterone-related tolerogenic findings are not proof of protection in human HT, and HT tissue evidence for B-cell activating factor (BAFF) and its receptor (BAFF-R) does not establish sex-specific therapeutic responsiveness. Clinical translation is therefore more limited than mechanistic plausibility. Established management remains based primarily on thyroid functional status and life-stage context, with levothyroxine as the standard treatment for overt hypothyroidism rather than a sex-specific immune intervention. Large randomized trials in euthyroid TPOAb-positive women have not shown improved live-birth outcomes with routine levothyroxine, while selenium, vitamin D and myo-inositol studies predominantly report biochemical or surrogate outcomes and do not establish sex-specific benefit. Published sex-related differences in TPOAb reference limits are method- and reference-population-dependent and should not be confused with validated HT diagnostic thresholds. Accordingly, sex-aware precision strategies are best viewed as a research framework requiring disease-specific biomarker validation, demonstration of incremental clinical utility, patient-relevant outcomes, and sex-stratified prospective trials before routine implementation.",
  "abstract_shown": true,
  "affiliations": [
    "Affiliated Central People's Hospital, China Three Gorges University",
    "Department of Endocrinology, Yichang Central People's Hospital",
    "Department of Pathology, Shantou University Medical College",
    "Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital, Southwest Medical University",
    "Department of Biliary-Pancreatic Center, The Affiliated Hospital, Southwest Medical University",
    "Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University",
    "The Third Affiliated Hospital, Qiqihar Medical University",
    "Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University",
    "Nuclear Medicine and Theranostics Key Laboratory of Sichuan Province",
    "Institute of Nuclear Medicine, Southwest Medical University",
    "Heilongjiang University of Chinese Medicine",
    "School of Basic Medical Sciences, Qiqihar Medical University",
    "Department of Oncology, Yichang Central People's Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yiwei Hou"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Yu Yang"
    },
    {
      "affs": [
        6
      ],
      "name": "Qiuyi Peng"
    },
    {
      "affs": [
        6
      ],
      "name": "Ye Liang"
    },
    {
      "affs": [
        7,
        8,
        9
      ],
      "name": "Li Yi"
    },
    {
      "affs": [
        6
      ],
      "name": "Ru Zheng"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhenjie Yang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zan Zhou"
    },
    {
      "affs": [
        10
      ],
      "name": "Dexiang Sha"
    },
    {
      "affs": [
        11
      ],
      "name": "Pengfei Liu"
    },
    {
      "affs": [
        0,
        12
      ],
      "name": "Shengyu Tang"
    },
    {
      "affs": [
        0,
        12
      ],
      "name": "Xiangyu Liao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wufei Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0m5n823by4ze0.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1924753",
  "fulltext_url": null,
  "id": "0m5n823by4ze0",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1924753/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0m5n823by4ze0.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:27Z",
      "native_id": "10.3389/fendo.2026.1924753",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1924753/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1664-2392",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Sex-related mechanisms underlying female predominance in Hashimoto’s thyroiditis: evidence gaps and implications for sex-aware clinical translation",
  "title_text": "Sex-related mechanisms underlying female predominance in Hashimoto’s thyroiditis: evidence gaps and implications for sex-aware clinical translation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:25Z",
  "url": "https://research.draconitic.com/paper/0m5n823by4ze0",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}