gestodene and Myocardial-Infarction

We reviewed evidence that bears on the cardiovascular safety of combined oral contraceptives containing second- and third-generation progestogens and < 50 micrograms of estrogen. Recent epidemiologic studies indicate that current use of these formulations is associated with a smaller increase in the incidence of venous thromboembolism than earlier formulations. In some studies the increase for third-generation formulations containing desogestrel or gestodene was about 1.5 to 2 times that for second-generation formulations, but there is evidence that differences between users in underlying risk and likelihood of being diagnosed contributed to this result. Recent studies of myocardial infarction suggest a smaller increase in risk associated with modern formulations than with earlier ones; one study suggests a threefold increase for second-generation formulations and no increase for third-generation formulations, but the finding requires confirmation. Recent studies of stroke indicate little or no increase in risk for modern formulations among women without risk factors. We conclude that modern combined oral contraceptives are safer than earlier formulations with respect to cardiovascular disease, which occurs rarely in young women.. This review of the research literature on the cardiovascular safety of oral contraceptives (OCs) containing less than 50 mcg of estrogen and second- or third-generation progestins suggests that these formulations are safer than earlier OCs were. Although some recent studies detected an increased risk of venous thromboembolism of 1.5-2.0 in users of OCs containing desogestrel or gestodene compared with second-generation progestins, these studies are marred by detection bias and the tendency for high-risk women to be prescribed third- rather than second-generation OCs. Studies of the association between combined OCs and myocardial infarction have yielded discrepant results; one found an increased risk with second- but not third-generation OCs. Studies on stroke indicate little or no increase in risk in users of modern OCs without other cardiovascular risk factors. Overall, the available research indicates that use of second- or third-generation OCs carries less risk of venous thromboembolism than pregnancy. In addition to the prevention of pregnancy and its attendant risks, low-dose OCs confer additional health benefits such as reductions in the incidence of ovarian and endometrial cancer.

Topics: Cardiovascular Diseases; Case-Control Studies; Cerebrovascular Disorders; Contraceptives, Oral, Combined; Desogestrel; Estrogens; Female; Follow-Up Studies; Humans; Incidence; Myocardial Infarction; Norpregnenes; Risk Factors; Thromboembolism; United States; United States Department of Agriculture; World Health Organization

The aim of this prospective cross-over study was to investigate the effect of two low-dosed oral contraceptives on markers of endothelial function and plasma lipids. Twelve healthy, nonsmoking women (mean age: 21.7 years) were recruited from the family planning clinic of the university hospital Zurich. For 6 months the participants received a treatment with two contraceptive pills containing 30 microg ethinyl estradiol/150 microg levonorgestrel (three cycles) and 30 microg ethinyl estradiol/75 microg gestodene (three cycles). Plasma levels of endothelin-1, nitric oxide, cholesterol, and HDL were measurement before and during treatment with both oral contraceptive treatments. No significant changes in the plasma levels of nitric oxide and endothelin-1, both important regulators of the vascular tone, were observed during oral contraceptive use. A significant negative correlation was found between nitric oxide and endothelin-1 and nitric oxide and cholesterol. There was a positive correlation between endothelin-1 and cholesterol. In conclusion, the investigated contraceptive pills did not cause major changes in circulating nitric oxide and endothelin-1 plasma levels.

Topics: Adult; Cholesterol, HDL; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Cross-Over Studies; Endothelin-1; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Myocardial Infarction; Nitric Oxide; Norpregnenes; Premenopause; Prospective Studies; Statistics, Nonparametric; Time Factors

-Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid arteries. Carotid IMT is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. This randomized, controlled, observer-blind, clinical, single-center trial enrolled 321 healthy postmenopausal women with increased IMT in >/=1 segment of the carotid arteries. For a period of 48 weeks, subjects received either 1 mg/d 17ss-estradiol continuously plus 0.025 mg gestodene for 12 days every month (standard-progestin group), or 1 mg 17ss-estradiol plus 0.025 mg gestodene for 12 days every third month (low-progestin group), or no HRT. Maximum IMT in 6 carotid artery segments (common, bifurcation, and internal, both sides) was measured by B-mode ultrasound before and after intervention. HRT did not slow IMT progression in carotid arteries. Mean maximum IMT in the carotid arteries increased by 0.02+/-0.05 mm in the no HRT group and by 0.03+/-0.05 and 0.03+/-0.05 mm, respectively, in the HRT groups (P:>0.2). HRT significantly decreased LDL cholesterol, fibrinogen, and follicle-stimulating hormone. In conclusion, 1 year of HRT was not effective in slowing progression of subclinical atherosclerosis in postmenopausal women at increased risk.

Topics: Carotid Arteries; Carotid Artery Diseases; Estradiol; Estrogen Replacement Therapy; Female; Humans; Myocardial Infarction; Norpregnenes; Risk Factors; Tunica Intima

An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations. In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls. The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation. The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.

Topics: Adolescent; Adult; Case-Control Studies; Contraceptives, Oral; Desogestrel; Ethinyl Estradiol; Factor V; Female; Humans; Levonorgestrel; Logistic Models; Middle Aged; Myocardial Infarction; Norpregnenes; Odds Ratio; Point Mutation; Prothrombin; Risk Factors; Smoking

Topics: Adolescent; Adult; Case-Control Studies; Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Myocardial Infarction; Norpregnenes; Risk Factors; Thromboembolism

The objective of this study was to assess the risk of myocardial infarction (MI) associated with the use of new and old combination oral contraceptives (OC). A matched case-control study in 16 centers in Germany, the United Kingdom, France, Austria, and Switzerland explored the association of current use of combination OC with the occurrence of MI. Our subjects were 182 women aged 16-44 years with MI; the controls were 635 women without MI (at least one hospital control and one community control per case) matched for 5-year age group and region. The main outcome measures were odds ratios comparing current use of a specific group of OC against current use of other groups or against no current use. The adjusted overall odds ratio (OR; 95% confidence intervals) for MI for second generation OC versus no current use was 2.35 (1.42 to 3.89) and 0.82 (0.29 to 2.31) for third generation OC (low dose ethinyl estradiol, gestodene, and desogestrel). A direct comparison of third generation users with second generation users yielded an OR of 0.28 (0.09 to 0.86). In subgroup analyses, the odds ratio for the UK alone was 1.25 (0.36 to 4.29), while for continental Europe it was 0.10 (0.02 to 0.48). For hospital controls, the risk estimated was 0.98 (0.22 to 4.44), and 0.18 (0.04 to 0.65) for community controls. The independent risk of MI among current smokers adjusted for OC use was 7.21 (4.58 to 11.36). Among users of third generation OC, the OR for current smokers was 3.75 (0.65 to 21.74) and among users of second generation it was 9.50 (2.93 to 30.96). A comparison of OC use in the UK for the time before and after regulatory action was taken in October 1995 shows that the likelihood of a control (last control accrued June 1996) being treated with second generation OC is seven times higher after 1 November 1995 than it was before. Third generation OC are the first to be associated with no excess risk of MI. A significantly lower risk of MI is found when comparing use of third generation OC with use of second generation OC. There seems to be an impressive amelioration of risk among smokers using newer OC. An impact of regulatory action in the UK was found in the OC use spectrum of controls.. The risk of myocardial infarction associated with use of second- and third-generation oral contraceptives (OCs) was investigated in a matched case-control study conducted at 16 centers in Germany, the UK, France, Austria, and Switzerland. 182 women 18-44 years old with myocardial infarction were matched for 5-year age group and region with 635 controls (at least 1 hospital control and 1 community control per case). 57 cases and 156 controls reported exposure to OCs, of whom 7 cases and 49 controls had taken third-generation formulations. The adjusted overall odds ratio (OR) for myocardial infarction was 2.35 (95% confidence interval [CI], 1.42-3.89) for second-generation OC use versus no use but only 0.82 (95% CI, 0.29-2.31) for third-generation OC use versus no use. A direct comparison of third-generation and second-generation OC users yielded an OR of 0.28 (95% CI, 0.09-0.86). 80% of cases, compared with 37% of controls, were current smokers. The independent risk of myocardial infarction among current smokers adjusted for OC use was 7.21 (95% CI, 4.58-11.36). The OR for current smokers was 3.75 (95% CI, 0.65-21.74) among users of third-generation OCs and 9.50 (95% CI, 2.93-30.96) among users of second-generation formulations. These Transnational Study findings indicate that third-generation formulations are the first OCs to be associated with no excess risk of myocardial infarction; moreover, they substantially reduce this risk among smokers. The reduced risk of myocardial infarction associated with OCs containing desogestrel and gestodene compared with levonorgestrel may reflect the failure of third-generation progestins to inhibit the estrogen-related increase in sex hormone binding globulin.

Topics: Adolescent; Adult; Austria; Case-Control Studies; Contraceptives, Oral; Desogestrel; Ethinyl Estradiol; Female; France; Germany; Humans; Myocardial Infarction; Norpregnenes; Odds Ratio; Progesterone Congeners; Risk Factors; Smoking; Switzerland; United Kingdom

Topics: Adult; Case-Control Studies; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Levonorgestrel; Myocardial Infarction; Norpregnenes; Progesterone Congeners; Risk; Smoking