Biological effects of progestins: focus on deep venous thrombosis risk

Abstract

Combined hormonal contraception containing estrogen and progestin and menopausal hormone therapy with estrogen plus progestins or estrogen alone are consistently reported risk factors for deep venous thrombosis (DVT) and, with less certainty, arterial thrombosis. The DVT risk associated with combined hormonal contraceptives (CHCs) appears to vary by route of administration, estrogen dose and type of progestin. CHCs containing low-dose estrogen (< 35 microgram ethinyl estradiol) combined with “newer generations” of progestins (e.g., desogestrel, gestodene and drospironone) may have a higher DVT risk than those containing low-dose estrogen combined with the older (second) generation progestin types (e.g., levonorgestrel). Among postmenopausal women, DVT risk also varies by estrogen type and mode of delivery. Among combined oral contraception (COC) users, the variation in DVT risk can be at least partially explained by differences in resistance to activated protein C (APC) as measured by thrombin generation based on the APC resistance test and quantified by means of a normalized APC sensitivity ratio. The net estrogenicity of COC may also serve as a risk marker for DVT as several studies have shown an association between clinical risk and levels of sex hormone-binding globulin during COC use. Similar findings have been obtained using measurements of factor VII-activating protease. Limited evidence suggests increased odds of DVT with the use of injectables and oral use of progestin-only contraception. Of note, however, even with the most expressed DVT risk demonstrated during COC use, any increase in relative risk translates to a small increase in absolute numbers of thrombotic events.

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