Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens

Epidemiological studies have shown that both the estrogen dose and progestogen type of oral contraceptives contribute to the increased risk of thrombosis in oral contraceptive users. Thrombin generation-based activated protein C (APC) sensitivity is a global test for the net prothrombotic effect of oral contraceptives and predicts the thrombotic risk. Our objective was to test the usefulness of sex hormone-binding globulin (SHBG) as a marker for the thrombotic risk of an oral contraceptive.We measured SHBG and APC resistance in 156 healthy users of various types of oral contraceptives.Users of oral contraceptives with a moderately increased risk of thrombosis (gestodene and desogestrel pills) had higher SHBG levels than users of low-risk oral contraceptives containing levonorgestrel. Similarly, for higher doses of estrogen in oral contraceptives we found higher SHBG levels. Women using oral contraceptives with the highest thrombotic risk (cyproterone acetate pills) rendered the highest SHBG levels. Users of oral contraceptives containing gestodene, desogestrel or cyproterone acetate were more resistant to APC than users of levonorgestrel pills. SHBG levels were positively associated with the increased APC resistance.Our findings support the hypothesis that the effect of an oral contraceptive on SHBG levels might be a marker for the thrombotic risk.