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

Abstract

To cite this article: Raps M, Helmerhorst F, Fleischer K, Thomassen S, Rosendaal F, Rosing J, Ballieux B, van Vliet H. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost 2012; 10: 992-7.Summary. 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.

MECHANISMS IN ENDOCRINOLOGY: Epidemiology of hormonal contraceptives-related venous thromboembolism

“…SHBG, which has been recently positively correlated with APC resistance among pill users, is another useful pharmacological marker to indirectly predict the venous thrombotic safety of a combined contraception (27,28,29). SHBG is a carrier protein synthesized by the liver.…”

“…The relationship between the effects on acquired resistance to APC in users of different types of COC parallels the effects on SHBG in users of those COCs (27). As APC-resistant SHBG appears to be higher among users of DSG, DRSP, and CPA containing pills than among users of LNG pills (27,28).…”

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial

“…containing GTD, DSG, CPA or DRSP) and oral contraceptives with a lower risk of venous thrombosis (i.e. containing LNG) [3,6,[9][10][11][12][13]15].…”

“…containing LNG) [3,6,[9][10][11][12][13]15]. Sex hormone binding globuline (SHBG) is another marker that differentiates between combined oral contraceptives with a high and low risk of venous thrombosis [15][16][17][18][19]. SHBG is a carrier protein, which is produced in the liver and binds estrogen and testosterone [20].…”

“…The effect of a hormonal contraceptive on SHBG is the net result of the estrogenic effect of estradiol and the antiestrogenic effect of the progestogen, yielding the total estrogenicity of that hormonal contraceptive. This estrogenicity serves as a marker for the thrombotic risk of a hormonal contraceptive [15][16][17][18].Recently, a new, four-phasic, combined oral contraceptive containing dienogest and estradiol valerate (Qlaira â ; Bayer Schering Pharma, Berlin, Germany) was marketed. Dienogest (DNG) is a progestogen derived from the estrane structure and has antiandrogenic and no androgenic properties [23].…”