Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study

J Thromb Haemost. 2012 Nov;10(11):2277-86. doi: 10.1111/j.1538-7836.2012.04919.x.


Background: Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk.

Methods: A total of 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).

Results: During 3.3 million years of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years after last reporting HT use. RRs in current vs. never users at last reporting varied by HT formulation: the risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91 [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first 2 years after starting HT than later (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate.

Conclusions: The risk of VTE varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate.

Keywords: cohort study; deep vein thrombosis; hormone therapy; progestagens; pulmonary embolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Drug Combinations
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / administration & dosage
  • Female
  • Hormones / therapeutic use*
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage
  • Middle Aged
  • Postmenopause
  • Progestins / administration & dosage
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • United Kingdom
  • Venous Thromboembolism / diagnosis*
  • Venous Thromboembolism / physiopathology*


  • Drug Combinations
  • Estrogens
  • Hormones
  • Progestins
  • Medroxyprogesterone Acetate