Oral Contraceptives and Venous Thromboembolism: Which Are the Safest Preparations Available?

Oral contraceptive therapy is associated with a fourfold increased risk of venous thromboembolism as compared with agematched non-users. The composition of oral contraceptives has varied considerably during the past two to three decades. The estrogen content (ethinylestradiol) has decreased and is now less than 0.03 mg/pill. This was done on the assumption that estrogen was the main culprit for thrombotic complications. Subsequently it was found that the progestins contained in the pill could also play a thrombogenic role. This was particularly maintained to be so for the third-generations progestins, namely gestodene or desogestrel. These gonane progestins have been widely used since the early 1990s, because they appeared to have a lesser androgenic effect. A careful and impartial evaluation of the literature seems to indicate that third-generation progestins are associated with a slight increase in thrombotic risk. However, the significance of this difference remains to be proven. In fact, a relative risk of only two in retrospective studies may have limited effect and disappear in prospectives studies. The role of associated risk factors, both congenital and acquired, has been often overlooked in most of the papers dealing with the subject. This may be important. Preparations containing third-generation progestins are probably associated with a slight increase in thrombosis risk. It is the responsibility of the physician to select the preparation most suited for a given patient. As a general rule it may be safe to start with a preparation containing second-generation progestins. However there is no need for “a pill scare” and it does not seem justified to have women already taking pills containing third-generation progestins to switch to other preparations. If a woman taking preparations containing third-generation progestins experience symptoms, it is probably safe to advise that patient not to take any oral contraceptive pill in the future, regardless of the type. The same is true for women who experience symptoms while taking second-generation progestins preparations.

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