Hormone replacement therapy and venous thromboembolism

J Steroid Biochem Mol Biol. 2014 Jul;142:76-82. doi: 10.1016/j.jsbmb.2013.08.016. Epub 2013 Sep 3.


Hormone replacement therapy (HRT) for post-menopausal women is known to promote venous thromboembolism (VTE), i.e., deep venous thrombosis and pulmonary embolism, though the absolute risk for a given patient is very small. The risk of VTE appears to be greatest soon after the initiation of HRT and returns to the baseline level of risk of non-HRT users after discontinuation. There is inconsistent data about whether estrogen-only or combined estrogen-progestin HRT are associated with similar VTE risk. Retrospective analyses suggest that transdermal HRT is not as prothrombotic as oral HRT, though this has not been evaluated in randomized clinical trials. Increasing age and weight further promote HRT's VTE risk. Some studies have investigated whether prothrombotic combinations may increase HRT's VTE risk and there is evidence that Factor V Leiden may do this. However, no benefit to screening prospective HRT users has been described, yet. Advanced proteomic and genomic studies may hold promise in the future for better elucidating which HRT users are at highest risk for VTE. Presently, physicians and prospective HRT users should discuss the potential risks and benefits for the individual patient, acknowledging there is no way to fully mitigate the risk of VTE. This article is part of a Special Issue entitled 'Menopause'.

Keywords: Deep venous thrombosis; Hormone replacement therapy; Venous thromboembolism, Pulmonary embolism, Factor V Leiden.

MeSH terms

  • Age Factors
  • Aged
  • Estrogen Replacement Therapy / adverse effects*
  • Factor V / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Obesity / complications
  • Retrospective Studies
  • Risk
  • Thrombophilia / complications
  • Thrombophilia / genetics
  • Venous Thromboembolism / chemically induced*
  • Venous Thromboembolism / genetics


  • factor V Leiden
  • Factor V

Supplementary concepts

  • Thrombophilia, hereditary