Postmenopausal hormone replacement therapy and venous thromboembolism

Gend Med. 2005:2 Suppl A:S18-27. doi: 10.1016/s1550-8579(05)80061-0.


Background: Women taking hormone replacement therapy (HRT) have a 2- to 5-fold increased risk of venous thrombosis compared with nonusers. Increasingly, evidence has suggested that the size of the risk increase varies according to related factors, such as the type of estrogen used, the mode of delivery, and the presence of other predisposing factors.

Objective: The aim of this study was to examine the current literature to assess the varying risk of venous thrombosis among women taking HRT.

Methods: An extensive search was carried out on all major electronic databases including MEDLINE 1995 to October 2005 and BIS (EMBASE) 1980 to October 2005. Relevant keywords relating to thrombosis (venous thromboembolism, venous thrombosis, deep vein thrombosis, and pulmonary embolism) combined with hormones (hormone replacement therapy and estrogen) were used to capture all potentially relevant studies.

Results: The increased risk of a first episode of venous thrombosis in women currently taking HRT compared with nonusers ranged from 1.22 (95% CI, 0.76-1.94) to 4.50 (95% CI, 1.30-15.10). Similar increases in risks for deep vein thrombosis and pulmonary embolism were found. The risk of venous thrombosis is the highest in the first year of therapy, durich which as much as a greater than 6-fold increase was found. Women taking estrogen-progestin HRT had a significantly greater risk of venous thrombosis than those using estrogen-only preparations (odds ratio [OR], 1.60; 95% CI, 1.13-2.26). Studies have also suggested a dose-related effect, suggesting high-dose estrogen therapy is associated with a greater increased risk of venous thrombosis than low-dose preparations. Comparisons between oral and transdermal HRT have shown a significant difference in the relative risk of venous thrombosis (OR, 4.0; 95% CI, 1.9-8.3) favoring the use of transdermal preparations. The presence of thrombophilia, particularly factor V Leiden, further amplifies the risk of venous thrombosis in women using HRT (OR, 13.16; 95% CI, 4.28-40.47). The presence of other risk factors, such as increasing age and being overweight, were all shown to be associated with a further increase in the risk of venous thrombosis.

Conclusions: Recent studies have confirmed that current users of HRT are at increased risk of venous thrombosis. The increase in risk has been shown to vary according to duration of use, with the risk being greatest during the first year of use. Moreover, the increased risk varies according to the type of preparation and presence of additional risk factors such as increasing age, obesity, cancer, and recent surgery. Few studies have examined the relationship between thrombophilia, HRT and venous thrombosis; thus, more research is required in this area before accurate estimates of the risk can be made.

Publication types

  • Review

MeSH terms

  • Aged
  • Confidence Intervals
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Odds Ratio
  • Postmenopause / metabolism*
  • Pulmonary Embolism / chemically induced*
  • Pulmonary Embolism / epidemiology
  • Pulmonary Embolism / prevention & control
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Venous Thrombosis / chemically induced*
  • Venous Thrombosis / epidemiology
  • Venous Thrombosis / prevention & control
  • Women's Health


  • Estrogens