Thyroid hormones and epithelial ovarian cancer risk and survival: results from the European Prospective Investigation into Cancer and Nutrition study

Abstract

Background: Thyroid-stimulating hormone (TSH) and thyroid hormones (free triiodothyronine [fT3] and free thyroxine [fT4]) may influence cancer outcomes, but evidence for ovarian cancer is limited.

Methods: We conducted a nested case-control study comparing 578 epithelial ovarian cancer (EOC) cases with matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). To examine associations between circulating TSH, fT3, and fT4 levels and EOC risk, we estimated risk ratios (RRs) and 95% confidence intervals (CIs) per SD using conditional logistic regression. Among cases, we evaluated all-cause and EOC-specific survival by prediagnostic hormone levels. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable Cox regression. We also estimated covariate-adjusted restricted mean survival time (RMST) and survival probabilities at 5 and 10 years.

Results: Thyroid hormones were not associated with EOC risk (RR [95% CI] per SD increase: TSH = 0.99 [0.87 to 1.12], fT3 = 1.12 [0.70 to 1.79], and fT4 = 1.08 [0.56 to 2.07]) levels. However, higher TSH levels were associated with better survival (HR [95% CI] per SD: all-cause death = 0.90 [0.82 to 0.99], EOC-specific = 0.88 [0.79 to 0.97]), whereas higher fT4 levels were associated with worse survival (all-cause = 1.10 [1.00 to 1.22], EOC-specific = 1.17 [1.05 to 1.30]), but no association for fT3. RMST and survival probabilities showed similar patterns: for TSH, 10-year RMST and survival increased from 5.3 years and 42.2% in Quartile 1 (Q1) to 6.4 years and 50.7% in Q4. Conversely, for fT4, 10-year RMST declined from 5.6 years (Q1) to 5.1 years Q4, and survival from 46.3% to 37.8%.

Conclusion: TSH and thyroid hormones might not affect ovarian cancer risk. However, high fT4 and low TSH concentrations may be associated with poorer survival. Further evaluation is suggested in other populations.