Reproductive Factors and Disease Progression in Differentiated Thyroid Cancer: A Large Retrospective Cohort Study of 1,098 Chinese Women

Background: Differentiated thyroid carcinoma (DTC) shows a marked female predominance, particularly during reproductive years, implicating sex hormones and reproductive factors in its pathogenesis. However, evidence regarding the impact of reproductive variables—such as age at menarche, parity, and pregnancy history—on disease progression remains inconsistent, especially in Chinese women. Large‑scale studies addressing this issue are limited. This study aimed to evaluate the association between reproductive history and clinicopathological aggressiveness in female patients with DTC. Methods: We conducted a single‑center retrospective cohort study of 1,098 female patients with DTC who underwent surgical resection between June 2014 and February 2024. Data on reproductive history and tumor characteristics were collected. Group comparisons were performed using standard statistical tests, and multivariable logistic regression was applied to adjust for confounders and estimate odds ratios (ORs) with 95% confidence intervals (CIs). The study was performed in accordance with the ethical principles of the Declaration of Helsinki and relevant institutional guidelines.The study was approved by the Institutional Review Board of Sichuan Cancer Hospital (SCCHEC‑02‑2025‑148), with informed consent waived. Results: Multivariable analysis identified early (≤11 years) and late menarche (≥15 years) as independent predictors of advanced clinical stage (OR=7.60, 95%CI:2.76–20.92; OR=3.10, 95%CI:1.31–7.35, respectively). Parity demonstrated a dose-response relationship with disease severity, with ≥3 births being the strongest predictor of advanced stage (OR=23.19, 95%CI:11.00–59.64). Nulliparity showed protective effects against advanced staging (OR=0.03, 95%CI:0.01–0.23).Reproductive factors exhibited compartment-specific nodal metastasis patterns: nulliparity associated with central compartment involvement (OR=1.69, 95%CI:1.25–2.28), while ≥5 pregnancies linked to lateral neck metastasis (OR=2.37, 95%CI:1.29–4.36). Parity ≥3 correlated with both local invasion (T3/T4: OR=4.12, 95%CI:2.13–7.97) and metastases in central (OR=3.81, 95%CI:1.67–8.69) and lateral neck compartments (OR=4.24, 95%CI:2.24–8.00). Conclusion: Abnormal menarche timing, multiple pregnancies, and high parity independently predict more advanced and aggressive DTC in Chinese women, with clear dose–response relationships. Incorporating reproductive history into clinical risk stratification may improve identification of high‑risk patients and guide individualized management.