Pre-diagnosis thyroid dysfunction and ovarian cancer risk and survival: a prospective cohort study

Thyroid hormones influence reproductive and metabolic pathways that may affect ovarian cancer development and progression. However, epidemiological evidence is limited and inconsistent. We examined the association between physician-diagnosed thyroid dysfunction and ovarian cancer risk and survival in a large prospective cohort.

We included 80,348 women from the E3N cohort who completed at least one biennial questionnaire enquiring about physician-diagnosed thyroid dysfunction (hyperthyroidism or hypothyroidism) between 1992 and 2014. We used Cox regression models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer incidence through 2018 and, among women diagnosed with ovarian cancer, for overall survival through 2024. Models were adjusted for established ovarian cancer risk or prognostic factors.

During follow-up (up to 2018), 589 ovarian cancer cases were identified. Overall, pre-diagnostic thyroid dysfunction was not associated with ovarian cancer risk. However, hypothyroidism diagnosed ≥5 years earlier was associated with reduced risk (HR = 0.65, 95% CI = 0.45-0.95) and hyperthyroidism diagnosed ≥5 years earlier and not using levothyroxine was associated with increased risk (HR = 1.70, 95%CI = 1.04-2.78). We found no meaningful association between pre-diagnostic thyroid dysfunction and survival following an ovarian cancer diagnosis.

Hypothyroidism may be associated with decreased ovarian cancer risk, and hyperthyroidism with increased ovarian cancer risk. Neither hyperthyroidism nor hypothyroidism appeared to affect survival. Whether these associations are causal or whether levothyroxine use plays a role in the development of cancer should be investigated further.