Menstrual and reproductive factors in the risk of thyroid cancer in Japanese women: the Japan Public Health Center-Based Prospective Study

Eur J Cancer Prev. 2018 Jul;27(4):361-369. doi: 10.1097/CEJ.0000000000000338.


The aim of this study was to evaluate the associations between menstrual and reproductive factors and thyroid cancer risk among Japanese women. A total 54 776 women aged 40-69 years completed a self-administered questionnaire, which included menstrual and reproductive history. During 1990-2012, 187 newly diagnosed cases of thyroid cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for menstrual and reproductive factors and incidence of thyroid cancer were estimated using Cox proportional hazards regression. Postmenopausal women who had natural menopause were at reduced risk of thyroid cancer than premenopausal women in the age-area-adjusted model (HR: 0.62 per 1 year increase, 95% CI: 0.39-0.99), but this association was slightly attenuated and no longer statistically significant in the multivariable-adjusted model. On analysis by menopausal status, an inverse association between age at menarche and risk of thyroid cancer was observed for premenopausal women (HR: 0.83 per 1 year increase, 95% CI: 0.70-0.98, P trend=0.03), but not for postmenopausal women. The risk of thyroid cancer increased with surgical menopause compared with natural menopause (HR: 2.34, 95% CI: 1.43-3.84). Although increasing age at menopause and duration of fertility were associated with an increased risk of thyroid cancer, this association was not observed among postmenopausal women. This study confirmed that early age at menarche for premenopausal women and surgical menopause and late age at natural menopause for postmenopausal women were associated with the development of thyroid cancer. Our results support the hypothesis that exposure to estrogens increases the risk of thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / drug therapy
  • Adenocarcinoma, Follicular / etiology*
  • Adenocarcinoma, Follicular / pathology
  • Adult
  • Aged
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Papillary / etiology*
  • Carcinoma, Papillary / pathology
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Japan
  • Menopause*
  • Menstruation
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Reproductive History*
  • Risk Factors
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / pathology