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Contraception. 1997 May;55(5):267-72.

Estrogen and progestin components of oral contraceptives: relationship to vascular disease.

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  • 1UT Southwestern Medical Center at Dallas, Department of Obstetrics and Gynecology 75235-9032, USA.

Abstract

Recently, new information has been published about: a) the relationship between combination oral contraceptives (OCs), estrogen dose, cigarette smoking, and the risk of myocardial infarction (MI) and stroke; and b) the effect of different progestins on the risk of venous thromboembolism (VTE). We review the epidemiologic data. Regardless of age, in the absence of smoking, use of sub-50 micrograms OCs is not associated with any meaningful increase in risk of MI or stroke. If the small, statistically nonsignificant elevations in risk for these diseases are assumed (for the sake of argument) to be causal, then the incidence of MI and stroke associated with use of OCs containing less than 50 micrograms ethinyl 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 history 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 nonhormonal contraceptive. There are now two reports, from jick et al. and Lewis et al., that demonstrate that the relative risk of MI is certainly no greater for users of OCs containing desogestrel or gestodene than for users of OCs containing older progestins. In fact, both show reduced relative risks for the newer progestins compared to the older ones. With respect to progestins, four recent epidemiologic studies have indicated a twofold increased risk of nonfatal VTE with use of OCs containing desogestrel or gestodene compared with levonorgestrel. A fifth report, which showed an increased relative risk for norgestimate, is based on use among only 19 cases and 31 controls and is not statistically significant. As the authors themselves caution and as subsequent follow-up analyses and editorials conclude, these studies do not provide evidence for a cause-and-effect relationship between OCs containing desogestrel or gestodene, and VTE. The recommendation with respect to desogestrel- and gestodene-containing OCs is that no change in prescribing practices is warranted for either current or new-start patients. There is a growing body of evidence demonstrating that OCs containing 30 or 35 micrograms of EE have lower risks of MI, stroke, and VTE than higher dose OCs. However, there is no epidemiologic study that demonstrates a greater risk of vascular events among women using OCs containing 30 or 35 micrograms EE compared with preparations containing 20 micrograms EE. Users of sub-50 micrograms OCs of any age have no clinically meaningful increase in incidence of MI or stroke compared with non-OC users. This is also true 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. Sub-50 micrograms 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 explanation of the twofold greater risk of VTE in users of OCs containing desogestrel or gestodene compared with users of those containing older progestins, this association should not be accepted as one of cause and effect.

PIP:

A review of the recent epidemiologic evidence indicates that use of low-dose combined oral contraceptives (OCs) is not associated with any clinically significant increase in risk of myocardial infarction (MI) or stroke, including for smokers under 35 years of age. Even if the small elevation in risk for these diseases is assumed to be causal, the incidence of both MI and stroke associated with use of OCs containing under 50 mcg of ethinyl estradiol would be only 2 per 100,000 events per year. This risk would be even lower for women under 35 years of age who do not smoke and have no history of hypertension. Two new reports have identified even lower relative risks of MI and stroke among users of OCs containing the progestins desogestrel and gestodene compared with users of second-generation OCs. However, four additional epidemiologic studies have revealed a two-fold increased risk of non-fatal venous thromboembolism for OCs containing desogestrel or gestodene compared to levonorgestrel; the excess risk is about 15 per 100,000 events per year. Until there is a biologic explanation of the greater thromboembolism risk in users of third-generation OCs, this association should not be viewed as causal and no change in OC prescribing practices is warranted for either current or new acceptors. However, smokers over 35 years of age should not use any combination OCs.

PMID:
9220222
[PubMed - indexed for MEDLINE]
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