Thyroid function and epithelial ovarian cancer risk and survival: evidence from two large prospective European cohorts — The Association Specialists
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  3. Thyroid function and epithelial ovarian cancer risk and survival: evidence from two large prospective European cohorts

Thyroid function and epithelial ovarian cancer risk and survival: evidence from two large prospective European cohorts (23597)

Azam Majidi 1 2 , Sabina Rinaldi 2 , Agnes Fournier 3 , Laure Dossus 2
  1. The Daffodil Centre, The University of Sydney, and Cancer Council NSW, Sydney, NSW, Australia
  2. Hormones and Metabolism team, Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), Lyon, , Lyon, France
  3. Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France

Background: Thyroid hormones influence cellular proliferation, metabolism, and apoptosis, and their receptors are expressed in ovarian tissue. Epidemiological evidence linking thyroid function with epithelial ovarian cancer (EOC) risk or survival has been inconsistent, partly due to differing approaches to assessing thyroid status. We examined both circulating hormone concentrations and clinically diagnosed thyroid dysfunction to provide an integrated evaluation of thyroid function in EOC aetiology and prognosis.

Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC; 578 cases and 1,135 matched controls), pre‑diagnostic circulating thyroid‑stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were analysed using conditional logistic regression for EOC risk and Cox regression and restricted mean survival time for overall and cancer‑specific survival. In the Étude Épidémiologique auprès de femmes de l’Éducation Nationale (E3N; 84,348 women, 589 cases, 391 deaths), physician‑diagnosed hyperthyroidism and hypothyroidism were modelled as time‑varying exposures, with secondary five‑year lagged analyses (not updating thyroid status during the five years before diagnosis to prevent bias due to reverse causation) and stratification by levothyroxine use to distinguish treated from persistent dysfunction.

Results: In EPIC (1), circulating TSH, fT3, and fT4 were not associated with EOC risk. However, higher pre‑diagnostic TSH was associated with improved survival, while higher fT4 predicted poorer survival. In E3N (2), no overall associations with EOC risk were observed. In lagged analyses, long‑standing hypothyroidism was associated with reduced risk (HR=0.65, 95%CI=0.45–0.95), and persistent, untreated hyperthyroidism with increased risk (HR=1.70, 95%CI=1.04–2.78). No meaningful associations with survival were identified in E3N.

Conclusion: Across these complementary cohorts, circulating thyroid hormone levels carried prognostic information for women with EOC, whereas sustained clinical thyroid dysfunction appeared more relevant to cancer risk. Together, these findings help clarify inconsistencies in prior evidence and highlight thyroid‑related pathways as potentially modifiable influences on EOC development and progression.

  1. 1. Azam Majidi, Sabina Rinaldi, [other authors], Agnès Fournier, Laure Dossus, Thyroid hormones and epithelial ovarian cancer risk and survival: results from the European Prospective Investigation into Cancer and Nutrition study, JNCI: Journal of the National Cancer Institute, Volume 117, Issue 11, November 2025, Pages 2343–2351, https://doi.org/10.1093/jnci/djaf222
  2. 2. Azam Majidi, Sabina Rinaldi, Therese Truong, Laure Dossus, Agnès Fournier, Pre-diagnosis thyroid dysfunction and ovarian cancer risk and survival: a prospective cohort study, JNCI: Journal of the National Cancer Institute, 2026;, djag055, https://doi.org/10.1093/jnci/djag055