The risk of venous thrombosis in women over 50 years old using oral contraception or postmenopausal hormone therapy

J Thromb Haemost. 2013 Jan;11(1):124-31. doi: 10.1111/jth.12060.


Background: Oral contraception (OC) and postmenopausal hormone therapy (HT) can be used to alleviate menopausal symptoms. However, the risk of venous thrombosis (VT) associated with OC use in women over 50 years old has never been assessed and the two preparations have not been directly compared.

Objectives: To determine and compare the risk of VT associated with OC and HT use.

Methods: From a large case-control study, 2550 women aged over 50 years old, 1082 patients with a first VT and 1468 controls, were included. Odds ratios (ORs) and 95% confidence intervals for VT were calculated for OC-users (164 patients and 54 controls) and HT-users (88 patients and 102 controls) compared with non-hormone users (823 patients and 1304 controls).

Results: OC-users had a 6.3-fold (4.6-9.8) increased risk of VT. This ranged from 5.4 (3.3-8.9) for preparations containing levonorgestrel to 10.2 (4.8-21.7) for desogestrel. The VT-risk associated with oral HT use was 4.0 (1.8-8.2) for conjugated equine estrogen combined with medroxyprogesterone acetate and 3.9 (1.5-10.7) for micronized estradiol combined with norethisterone acetate. Non-oral HT did not increase the risk of VT: OR 1.1 (0.6-1.8). Relative risk estimates were further increased in hormone users with factor V Leiden, prothrombin G20210A or blood group non-O and hormone users with a family history of VT.

Conclusions: In this study, non-oral HT seemed to be the safest hormonal preparation in women over 50 years old. OC use increased the VT risk the most, especially in women with inherited thrombophilia or a family history of VT.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Age Factors
  • Aged
  • Case-Control Studies
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Desogestrel / adverse effects
  • Estradiol / adverse effects
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / administration & dosage
  • Estrogens / adverse effects*
  • Estrogens, Conjugated (USP) / adverse effects
  • Female
  • Humans
  • Levonorgestrel / adverse effects
  • Logistic Models
  • Medroxyprogesterone Acetate / adverse effects
  • Middle Aged
  • Netherlands / epidemiology
  • Norethindrone / adverse effects
  • Norethindrone / analogs & derivatives
  • Norethindrone Acetate
  • Odds Ratio
  • Postmenopause
  • Progestins / administration & dosage
  • Progestins / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Transdermal Patch
  • Venous Thrombosis / chemically induced*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / epidemiology


  • Contraceptives, Oral, Hormonal
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progestins
  • Estradiol
  • Levonorgestrel
  • Desogestrel
  • Norethindrone Acetate
  • Medroxyprogesterone Acetate
  • Norethindrone