Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives

J Thromb Haemost. 2012 Jun;10(6):992-7. doi: 10.1111/j.1538-7836.2012.04720.x.


Background: It takes many years to obtain reliable values for the risk of venous thrombosis of hormonal contraceptive users from clinical data. Measurement of activated protein C (APC) resistance via thrombin generation is a validated test for determining the thrombogenicity of hormonal contraceptives. Sex hormone-binding globulin (SHBG) might serve as a marker for the risk of venous thrombosis, and can be easily and rapidly measured in routine laboratories.

Objective: To determine whether SHBG is a useful marker for the thrombotic risk of hormonal contraceptive users by comparing plasma SHBG levels with normalized APC sensitivity ratio (nAPCsr) values and thrombosis risks reported in the recent literature.

Methods: We conducted an observational study in 262 users of different contraceptives, and measured nAPCsr and SHBG levels.

Results: Users of contraceptives with a higher risk of causing venous thrombosis, i.e. combined hormonal contraceptives containing desogestrel, cyproterone acetate or drospirenone, and the transdermal patch, had higher SHBG levels than users of combined hormonal contraceptives containing levonorgestrel, which carry a lower thrombosis risk. Users of the patch had the highest SHBG levels, with a mean difference of 246 nmol L(-1) (95% confidence interval 179-349) from that in users of levonorgestrel-containing combined hormonal contraceptives. SHBG levels were positively associated with both the nAPCsr and the risks of venous thrombosis reported in the recent literature.

Conclusion: SHBG is a useful marker with which to estimate the thrombotic safety of a preparation.

Publication types

  • Comparative Study

MeSH terms

  • Activated Protein C Resistance / blood
  • Activated Protein C Resistance / chemically induced
  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Biomarkers / blood
  • Blood Coagulation / drug effects*
  • Blood Coagulation Tests
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects*
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Hormonal / adverse effects
  • Female
  • Humans
  • Intrauterine Devices
  • Middle Aged
  • Netherlands
  • Odds Ratio
  • Predictive Value of Tests
  • Protein C / metabolism
  • Regression Analysis
  • Risk Assessment
  • Risk Factors
  • Sex Hormone-Binding Globulin / metabolism*
  • Thrombin / metabolism
  • Transdermal Patch
  • Venous Thrombosis / blood
  • Venous Thrombosis / chemically induced*
  • Young Adult


  • Biomarkers
  • Contraceptive Agents, Female
  • Contraceptives, Oral, Combined
  • Contraceptives, Oral, Hormonal
  • Protein C
  • Sex Hormone-Binding Globulin
  • Thrombin