Associations of hormonal contraceptives and infertility medications on the risk of venous thromboembolism, ischemic stroke, and cardiovascular disease in women

J Investig Med. 2019 Apr;67(4):729-735. doi: 10.1136/jim-2018-000750. Epub 2018 Nov 26.


The purpose of this study was to examine the relations of hormonal contraceptives and infertility drugs with the risk of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and cardiovascular disease. The Taiwan National Health Institute Research Database was searched for women who had taken hormonal contraceptives or infertility medications from 2000 to 2010. The two groups were age and index date matched with controls (1:4 ratios). Cox regression analysis was used to examine the risks of VTE, DTE, PE, ischemic stroke, and cardiovascular disease. A total of 32,067 women were included in the hormonal contraceptives group and 4710 in the infertility medications group (matched controls: 127,872 and 18,840, respectively). After adjustment for age, comorbidities, and other confounders, the contraceptives group had a higher risk of VTE (adjusted HR 1.14, 95% CI 1.004 to 1.30) and cardiovascular disease (adjusted HR 1.30, 95% CI 1.26 to 1.34), and lower risk of ischemic stroke (adjusted HR 0.90, 95% CI 0.86 to 0.95). The infertility medications group had a higher risk of VTE (adjusted HR 1.996, 95% CI 1.41 to 2.72) and DVT (adjusted HR 1.86, 95% CI 1.31 to 2.63), and lower risk of ischemic stroke (adjusted HR 0.82, 95% CI 0.68 to 0.99) and cardiovascular disease (adjusted HR 0.83, 95% CI 0.74 to 0.94). Hormonal contraceptives and infertility medications appear to lower the risk of ischemic stroke and increase the risk of VTE; however, their effect on the risk of other types of cardiovascular events varies.

Keywords: cardiovascular disease; deep vein thrombosis; hormonal contraceptives; infertility; ischemic stroke; venous thromboembolism.

MeSH terms

  • Brain Ischemia / chemically induced*
  • Brain Ischemia / epidemiology
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Contraceptive Agents / adverse effects*
  • Female
  • Fertility Agents / adverse effects*
  • Humans
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / chemically induced*
  • Stroke / epidemiology
  • Venous Thromboembolism / chemically induced*
  • Venous Thromboembolism / epidemiology


  • Contraceptive Agents
  • Fertility Agents