ESTROGEN AND PROGESTIN COMPONENTS OF ORAL-CONTRACEPTIVES - RELATIONSHIP TO VASCULAR-DISEASE

Recently, new information has been published about: a) the relationshi p between combination oral contraceptives (OCs), estrogen dose, cigare tte smoking, and the risk of myocardial infarction (MI) and stroke; an d b) the effect of different progestins on the risk of venous thromboe mbolism (VTE). We review the epidemiologic data. Regardless of age, in the absence of smoking, use of sub-50 mu g OCs is not associated with any meaningful increase in risk of MI or stroke. If the small, statis tically nonsignificant elevations in risk for these diseases are assum ed (for the sake of argument) so be causal, then the incidence of MI a nd stroke associated with use of OCs containing less than 50 mu g ethi nyl estradiol (EE) would be approximately 2 per 100,000 per year. For women less than 35 years of age who do not smoke or do not have a hist ory of hypertension, the risk would be even lower. Any woman over the age of 35 who smokes should be advised to use a non-estrogen or nonhor monal contraceptive. There are now two reports, from lick et al. and L ewis et al., that demonstrate that the relative risk of MI is certainl y no greater for users of OCs containing desogestrel or gestodene than for users of OCs containing older progestins. In fact, both show redu ced relative risks for the newer progestins compared to the older ones . With respect to progestins, four recent epidemiologic studies have i ndicated a twofold increased risk of nonfatal VTE with use of OCs cont aining desogestrel or gestodene compared with levonorgestrel. A fifth report, which showed an increased relative risk for norgestimate, is b ased on use among only 19 cases and 31 controls and is not statistical ly significant. As the authors themselves caution and as subsequent fo llow-up analyses and editorials conclude, these studies do not provide evidence for a cause-and-effect relationship between OCs containing d esogestrel or gestodene, and VTE. The recommendation with respect to d esogestrel- and gestodene-containing OCs is that no change in prescrib ing practices is warranted for either current or new-start patients. T here is a growing body of evidence demonstrating that OCs containing 3 0 or 35 mu g of EE have lower risks of MI, stroke, and VTE than higher dose OCs. However, there is no epidemiologic study that demonstrates a greaser risk of vascular events among women using OCs containing 30 or 35 mu g EE compared with preparations containing 20 mu g EE Users o f sub-50 mu g OCs of any age have no clinically meaningful increase in incidence of MI or stroke compared with non-OC users. This is also tr ue for smokers under the age of 35 years who use OCs. However, smokers over the age of 35 years who use OCs still have an unacceptably high incidence rate of MI and stroke and should not use combination OCs. Su b-50 mu g OCs of all types are associated with a small excess risk of VTE, about 15 per 100,000 events per year. Until there is biologic exp lanation of the twofold greater risk of VTE in users of OCs containing desogestrel or gestodene compared with users of those containing olde r progestins, this association should not be accepted as one of cause and effect. (C) 1997 Elsevier Science Inc. All rights reserved.