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Estrogen and progestin components of oral contraceptives: relationship to vascular disease.
Contraception. 1997 May; 55(5):267-72.C

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.

Authors+Show Affiliations

UT Southwestern Medical Center at Dallas, Department of Obstetrics and Gynecology 75235-9032, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

9220222

Citation

Carr, B R., and H Ory. "Estrogen and Progestin Components of Oral Contraceptives: Relationship to Vascular Disease." Contraception, vol. 55, no. 5, 1997, pp. 267-72.
Carr BR, Ory H. Estrogen and progestin components of oral contraceptives: relationship to vascular disease. Contraception. 1997;55(5):267-72.
Carr, B. R., & Ory, H. (1997). Estrogen and progestin components of oral contraceptives: relationship to vascular disease. Contraception, 55(5), 267-72.
Carr BR, Ory H. Estrogen and Progestin Components of Oral Contraceptives: Relationship to Vascular Disease. Contraception. 1997;55(5):267-72. PubMed PMID: 9220222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen and progestin components of oral contraceptives: relationship to vascular disease. AU - Carr,B R, AU - Ory,H, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez KW - Biology KW - Blood Coagulation Effects KW - Cardiovascular Effects KW - Contraception KW - Contraceptive Methods--pharmacodynamics KW - Diseases KW - Embolism KW - Evaluation KW - Family Planning KW - Heart Diseases KW - Hematological Effects KW - Hemic System KW - Literature Review KW - Myocardial Infarction KW - Oral Contraceptives, Combined--pharmacodynamics KW - Oral Contraceptives--pharmacodynamics KW - Physiology KW - Risk Assessment KW - Thromboembolism KW - Vascular Diseases SP - 267 EP - 72 JF - Contraception JO - Contraception VL - 55 IS - 5 N2 - 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. SN - 0010-7824 UR - https://www.unboundmedicine.com/medline/citation/9220222/Estrogen_and_progestin_components_of_oral_contraceptives:_relationship_to_vascular_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0010782497000292 DB - PRIME DP - Unbound Medicine ER -