A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones

Cancer Causes Control. 1999 Apr;10(2):157-66. doi: 10.1023/a:1008832513932.


Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe.

Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity.

Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment.

Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma, Papillary / epidemiology*
  • Adenocarcinoma, Papillary / etiology*
  • Adolescent
  • Adult
  • Age Distribution
  • Age of Onset
  • Aged
  • Asia / epidemiology
  • Case-Control Studies
  • Confidence Intervals
  • Contraceptives, Oral / adverse effects*
  • Europe / epidemiology
  • Female
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Incidence
  • Logistic Models
  • Middle Aged
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Thyroid Neoplasms / epidemiology*
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / pathology
  • United States / epidemiology


  • Contraceptives, Oral