Share this article on:

00005768-199601000-0000500005768_1996_28_11_burkman_cardiovascular_1miscellaneous< 41_0_3_0 >Medicine & Science in Sports & Exercise©1996The American College of Sports MedicineVolume 28(1)January 1996pp 11,12Oral contraceptive use and coronary and cardiovascular risk[Roundtable Discussion]BURKMAN, RONALD T.Section Editor(s): Wenger, Nanette K.; Drinkwater, Barbara L.Oral contraception is the most popular nonpermanent contraceptive approach, with about 49% of women intending to have a future pregnancy relying on this method in the United States (6). Oral contraceptives have undergone substantial change since their introduction in the early 1960s. Most utilized ethinyl estradiol as the estrogen; the progestins varied, but all have been 19-nortestosterone derivatives. This derivation of the progestins has led to the inherent androgenicity in many preparations. Although the structural content has varied during the past two decades, the most substantive change has been the reduction of dosages by a factor of three- to four-fold for both the estrogen and progestin components(6,10). These changes have had significant impact both on cardiovascular risk and overall safety. However, at the same time, there have been substantial demographic changes in the United States. The number of U.S. women in their 30s and 40s is greater than any time in history(4). Further, as women age, they may acquire risk factors for cardiovascular disease such as diabetes and hypertension, or may experience increased cardiovascular risk due to lifestyle habits such as cigarette smoking that interact adversely with oral contraceptive use(10,11). Thus, these interactions pose potential concerns when one examines the risk of cardiovascular sequelae with oral contraception for these women.Thromboembolism was the first major sequela identified in association with oral contraceptive use (6). Early research demonstrated an estrogen dose effect, with the higher dose preparations showing significantly more risk of thromboembolism than medium dose preparations. More recent literature suggests that, with the further estrogen dosage reduction in current formulations to 35 μg of ethinyl estradiol or less, the overall risk of thromboembolism has been further reduced to the extent that it is of little consequence for most users (5). Although the risk of thrombotic stroke persists, dosage reduction has led to some reduction of risk for some oral contraceptive users (9). In most analyses of hemorrhagic stroke, oral contraceptive use is no longer a significant risk factor (9,10).Coronary atherosclerotic heart disease has also been extensively studied in regard to these agents. Most of the attention was initially focused on the effects these agents had on lipid and lipoprotein levels(8). The estrogen component exerts primarily a favorable effect on lipid and lipoprotein levels, that is, HDL-C levels rise and LDL-C levels fall. Although triglyceride levels also rise, they seldom reach levels considered to be of clinical significance (4). In contrast, most progestins, particularly 19-nortestosterone derivatives, have an opposite effect, e.g., LDL-C levels rise while HDL-C levels fall(8). It appears that both the structure and dose of the progestin determine the extent of this effect; further, the positive estrogen effects counterbalance the negative progestin effects in given preparations. The newest generation of oral contraceptives containing desogestrel, gestodene, or norgestimate as the progestin appear to have neutral and even some favorable effects on key lipid and lipoprotein levels; these preparations have less effect on the lipid/lipoprotein system in the usual doses utilized in oral contraceptives (13). Moreover, recent contraceptive steroid research with cynomolgus monkeys indicates that direct effects of estrogen on arterial vessel walls leads to less atherosclerotic changes in treated animals compared with controls, even where lipid and lipoprotein changes may be in an adverse direction(1,2). Additional experiments with this primate model have suggested that a major action of estrogen in oral contraceptive preparations is to inhibit the uptake of cholesterol into blood vessel walls(2). This latter effect may ultimately be more important than the changes in circulating lipid and lipoprotein levels in determining coronary atherosclerotic heart disease risk (or even protection) with these drugs.Clinical data document some risk of coronary heart disease among some users of oral contraceptives (3,6,11,12). The vast majority of cases are confined to older users who also smoke more than one pack of cigarettes per day or who have other cardiovascular risk factors. The risk of myocardial infarction essentially disappears once smoking is stopped; this finding suggests that myocardial infarctions experienced by current users of oral contraceptives are perhaps more thromboembolic than atherosclerotic. Among women who are former oral contraceptive users and who are now in their 50s, there is no evidence that prior oral contraceptive use increases future risk of coronary disease (14). This finding lends support to the primate data previously discussed. Finally, there are emerging data that suggest oral contraceptive use may even protect against the development of coronary heart disease; this finding, if confirmed in additional studies, could have significant public health impact(7).In summary, today's oral contraceptives are exceeding safe and effective. The concerns about cardiovascular risks which were prevalent in the 1970s and 1980s have substantially been put to rest for the vast majority of users. Although aging of women in the contraceptive use group has raised theoretical concerns about cardiovascular risk, there is no evidence of undue clinical sequelae. Further, if one interjects the significant noncontraceptive benefits such as reduction of endometrial and ovarian cancer, the benefit-risk ratio clearly is heavily weighted on the benefit side for most oral contraceptive users (10).REFERENCES1. Adams, M. R., T. B. Clarkson, D. R. Koritnik, et al. Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. Fertil. Steril. 47:1010-1018, 1987. [Medline Link] [Context Link]2. Clarkson, T. B., C. A. Shively, T. M. Morgan, et al. Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys.Obstet. Gynecol. 75:217-222, 1990. [Full Text] [Medline Link] [Context Link]3. Croft, P. and P. C. Hannaford. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. Br. Med. J. 298:165-168, 1989. [CrossRef] [Medline Link] [Context Link]4. Forrest, J. D. and S. Singh. The sexual and reproductive behavior of American women, 1982-1988. Fam. Plann. Perspect. 22:206-214, 1990. [CrossRef] [Medline Link] [Context Link]5. Gerstman, B. B., J. M. Piper, D. K. Tomita, et al. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am. J. Epidemiol. 133:32-37, 1991. [Medline Link] [Context Link]6. Harlap, S., K. Kost, and J. D. Forrest. Preventing Pregnancy, Protecting Health: A New Look at Birth Control Choices in the United States. New York: The Alan Guttmacher Institute, 1991. [Context Link]7. Hirvonen, E. and J. Idanpaan-Heikkila. Cardiovascular death among women under 40 years of age using low-estrogen oral contraceptives and intrauterine devices in Finland from 1975 to 1984. Am. J. Obstet. Gynecol. 163:281-284, 1990. [CrossRef] [Medline Link] [Context Link]8. Knopp, R. H., J. C. Larosa, and R. T. Burkman. Contraception and dyslipidemia. Am. J. Obstet. Gynecol. 168:1994-2005, 1993. [CrossRef] [Full Text] [Medline Link] [Context Link]9. Lidegaard, O. Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study. Br. Med. J. 306:956-963, 1993. [CrossRef] [Full Text] [Medline Link] [Context Link]10. Peterson, H. B. and N. C. Lee. The health effects of oral contraceptives: misconceptions, controversies, and continuing good news.Clin. Obstet. Gynecol. 32:339-355, 1989. [CrossRef] [Full Text] [Medline Link] [Context Link]11. Rosenberg, L., D. W. Kaufman, S. P. Helmrich, D. R. Miller, P. D. Stolley, and S. Shapiro. Myocardial infarction and cigarette smoking in women younger than 50 years of age. J.A.M.A. 253:2965-2969, 1985. [CrossRef] [Medline Link] [Context Link]12. Rosenberg, L., J. R. Palmer, S. M. Lesko, et al. Oral contraceptive use and the risk of myocardial infarction. Am. J. Epidemiol. 131:1009-1016, 1990. [Medline Link] [Context Link]13. Speroff, L., A. Decherney, R. T. Burkman, et al. Evaluation of a new generation of oral contraceptives. Obstet. Gynecol. 81:1034-1047, 1993. [Full Text] [Medline Link] [Context Link]14. Stampfer, M. J., W. C. Willett, G. A. Colditz, et al. Past use of oral contraceptives and cardiovascular disease: a meta-analysis in the context of the Nurses' Health Study. Am. J. Obstet. Gynecol. 163:285-291, 1990. [CrossRef] [Medline Link] [Context Link]Section DescriptionExercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors Nanette K. Wenger: Preventive Coronary Interventions for Women Udho Thadani: Hypertension and Cardiovascular Disease Risk in Women Steven N. Blair: Physical Inactivity and Cardiovascular Disease Risk in Women Ronald T. Burkman: Oral Contraceptive Use and Coronary and Cardiovascular Risk Margo A. Denke: Lipids, Estrogen Status, and Coronary Heart Disease Risk in Women Caren Solomon: Diabetes Mellitus and Risk of Cardiovascular Disease in Women Murray Freedman: Postmenopausal Hormone Replacement Therapy and Cardiovascular Disease RiskThis mongraph is based on the proceedings of an ACSM Roundtable entitled“Exercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors,” held June 21-22, 1994, in Indianapolis, Indiana.The Exercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors Roundtable was funded through a grant from Wyeth-Ayerst|00005768-199601000-00005#xpointer(id(R1-5))|11065405||ovftdb|SL00003748198747101011065405P15[Medline Link]|00005768-199601000-00005#xpointer(id(R2-5))|11065404||ovftdb|00006250-199002000-00018SL0000625019907521711065404P16[Full Text]|00005768-199601000-00005#xpointer(id(R2-5))|11065405||ovftdb|00006250-199002000-00018SL0000625019907521711065405P16[Medline Link]|00005768-199601000-00005#xpointer(id(R3-5))|11065213||ovftdb|SL00002591198929816511065213P17[CrossRef]|00005768-199601000-00005#xpointer(id(R3-5))|11065405||ovftdb|SL00002591198929816511065405P17[Medline Link]|00005768-199601000-00005#xpointer(id(R4-5))|11065213||ovftdb|SL0000371819902220611065213P18[CrossRef]|00005768-199601000-00005#xpointer(id(R4-5))|11065405||ovftdb|SL0000371819902220611065405P18[Medline Link]|00005768-199601000-00005#xpointer(id(R5-5))|11065405||ovftdb|SL0000042919911333211065405P19[Medline Link]|00005768-199601000-00005#xpointer(id(R7-5))|11065213||ovftdb|SL00000447199016328111065213P21[CrossRef]|00005768-199601000-00005#xpointer(id(R7-5))|11065405||ovftdb|SL00000447199016328111065405P21[Medline Link]|00005768-199601000-00005#xpointer(id(R8-5))|11065213||ovftdb|00000447-199306001-00005SL000004471993168199411065213P22[CrossRef]|00005768-199601000-00005#xpointer(id(R8-5))|11065404||ovftdb|00000447-199306001-00005SL000004471993168199411065404P22[Full Text]|00005768-199601000-00005#xpointer(id(R8-5))|11065405||ovftdb|00000447-199306001-00005SL000004471993168199411065405P22[Medline Link]|00005768-199601000-00005#xpointer(id(R9-5))|11065213||ovftdb|00002591-199304100-00007SL00002591199330695611065213P23[CrossRef]|00005768-199601000-00005#xpointer(id(R9-5))|11065404||ovftdb|00002591-199304100-00007SL00002591199330695611065404P23[Full Text]|00005768-199601000-00005#xpointer(id(R9-5))|11065405||ovftdb|00002591-199304100-00007SL00002591199330695611065405P23[Medline Link]|00005768-199601000-00005#xpointer(id(R10-5))|11065213||ovftdb|00003081-198906000-00019SL0000308119893233911065213P24[CrossRef]|00005768-199601000-00005#xpointer(id(R10-5))|11065404||ovftdb|00003081-198906000-00019SL0000308119893233911065404P24[Full Text]|00005768-199601000-00005#xpointer(id(R10-5))|11065405||ovftdb|00003081-198906000-00019SL0000308119893233911065405P24[Medline Link]|00005768-199601000-00005#xpointer(id(R11-5))|11065213||ovftdb|SL000054071985253296511065213P25[CrossRef]|00005768-199601000-00005#xpointer(id(R11-5))|11065405||ovftdb|SL000054071985253296511065405P25[Medline Link]|00005768-199601000-00005#xpointer(id(R12-5))|11065405||ovftdb|SL000004291990131100911065405P26[Medline Link]|00005768-199601000-00005#xpointer(id(R13-5))|11065404||ovftdb|00006250-199306000-00027SL00006250199381103411065404P27[Full Text]|00005768-199601000-00005#xpointer(id(R13-5))|11065405||ovftdb|00006250-199306000-00027SL00006250199381103411065405P27[Medline Link]|00005768-199601000-00005#xpointer(id(R14-5))|11065213||ovftdb|SL00000447199016328511065213P28[CrossRef]|00005768-199601000-00005#xpointer(id(R14-5))|11065405||ovftdb|SL00000447199016328511065405P28[Medline Link]2142573Oral contraceptive use and coronary and cardiovascular riskBURKMAN, RONALD T.Roundtable Discussion128