gestodene and Thromboembolism

Topics: Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Meta-Analysis as Topic; Norpregnenes; Risk Factors; Thromboembolism; Venous Thrombosis

Research on the relationship between venous thromboembolism and the progestagen content of combined oral contraceptives has pointed to an increase in risk associated with products containing desogestrel and gestodene. Although many biases must have been at play in these nonexperimental studies, the errors that have been suggested and examined are not of a sufficient magnitude to account for the observed results. The most plausible explanation of the available data is that combined oral contraceptives containing desogestrel and gestodene carry a very small risk of venous thromboembolism, which exceeds the even smaller risk carried by products containing levonorgestrel. The position of norgestimate is uncertain.. In October 1995, the UK Committee on the Safety of Medicines announced, in response to still unpublished studies, that third-generation oral contraceptives (OCs) carried an elevated risk of venous thromboembolism. The research motivating this announcement was subsequently published and criticized widely for its methodology. These critiques have focused on the possibility of selective prescribing of third-generation OCs to high-risk women, preferential diagnosis of venous thromboembolism in mildly symptomatic users of these OCs, and a tendency of high-risk women to shift from older to newer products. This article reviews the available data (World Health Organization Collaborative Study, General Practice Research Data Base, Leiden Thrombophilia Study, and the Transnational Study), evaluates competing explanations, and offers a summary interpretation. Overall, the review suggests that the errors identified are not of sufficient magnitude to account for the observed results. The preponderance of scientific evidence supports the proposition that desogestrel and gestodene do, in fact, carry a very small risk of venous thromboembolism that exceeds that associated with levonorgestrel.

Topics: Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Norpregnenes; Progesterone Congeners; Risk Factors; Thromboembolism; World Health Organization

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

Topics: Adult; Desogestrel; Female; Humans; Incidence; Norpregnenes; Progesterone Congeners; Thromboembolism

To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism.. Matched case-control study.. 10 centres in Germany and United Kingdom.. Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting.. Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables.. Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year.. Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Topics: Adolescent; Adult; Case-Control Studies; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Female; Germany; Humans; Norpregnenes; Odds Ratio; Risk Factors; Thromboembolism; United Kingdom

In the present study the effect of oral contraceptive (OC) treatment on selected factors involved in the activation, i.e. circulating activated factor VII (cFVIIa), and in the inhibition of blood coagulation, i.e. plasma protein S activity and circulating thrombomodulin (cTM), were for the first time measured in OC users in a prospective study. Beside other coagulation variables, these parameters were measured during treatment with three low estrogen formulations containing different gestagen components (norgestimate, gestodene). During OC treatment increases in the activation markers prothrombin fragment F1 + 2 and D-Dimer were found, suggesting an increased activation of blood coagulation and fibrinolysis. Along with elevated plasma levels of FVII antigen, cFVIIa was also found increased in all three treatment groups, while inhibitory components of blood coagulation, plasma protein S activity and cTM, significantly and similarly decreased during treatment in all three treatment groups. We conclude that low dose estrogen pills induce similar changes in the plasma levels of main regulatory components of blood coagulation, despite differences in their gestagen components. Increased levels of activators and decreased activities of inhibitors may contribute to arterial and venous thrombotic complications seen in predisposed OC users.. The effect of oral contraceptive (OC) treatment on selected factors involved in the activation and inhibition of blood coagulation was measured in a prospectively randomized parallel-group centralized-center study. These were circulating activated factor VII (cFVIIa) as well as plasma protein S activity and circulating thrombomodulin (cTM). In addition to other coagulation variables these parameters were measured during treatment with 3 low-estrogen formulations containing different gestagen components (norgestimate, gestodene). 60 healthy women 19-37 years old were included. The women in Group I used Cileste tablets containing 35 mcg ethinyl estradiol (EE) and 250 mcg norgestimate (NG). Group II women used the 3-phase preparation Tri-Cileste containing EE and different doses of NG; and Group II women used the 3-phase preparation Triodena containing different doses of EE and gestodene (GS). 21 days on treatment were followed by 7 days off of treatment before the next cycle was started. Participants were treated for 6 cycles. Blood samples were obtained during the luteal phase before treatment and on days 18-22 of the 3rd and 6th treatment cycle. The plasma levels of various coagulation parameters, such as fibrinogen (Cileste, Tri-Cileste p 0.05; Triodena p 0.0005); fibrin-split product D-Dimer (Cileste p 0.05; Tri-Cileste, Triodena p 0.005), prothrombin fragment F1+2 (Cileste p 0.0005); Tri-Cileste, Triodena p 0.05); Factor VII antigen (Cileste, Triodena p 0.0005; Tri-Cileste p 0.005); FVII clotting activity (Cileste p 0.0005; Tri-Cileste p 0.05; Triodena p 0.005), and activated factor VII (Cileste p 0.0005; Tri-Cileste p 0.05; Triodena p 0.005) were significantly higher during the 3rd treatment cycle compared with the pretreatment values. A significant decrease was also found in the plasma levels of total and free protein S antigen (total protein S: Cileste p 0.05; Tri-Cileste, Triodena p 0.005; free protein S: Cileste, Tri-Cileste p 0.0005; Triodena p 0.05) and circulating thrombomodulin (Cileste p 0.05; Tri-Cileste p 0.0005; Triodena p 0.005).

Topics: Adult; Blood Coagulation; Blood Proteins; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Ethinyl Estradiol; Factor VIIa; Female; Humans; Norgestrel; Norpregnenes; Prospective Studies; Protein S; Risk Factors; Thromboembolism; Thrombomodulin

Efficacy, cycle control, tolerance, and adverse events were studied in a clinical Phase IV study using a new progestogen, gestodene, in an amount of 75 micrograms combined with 30 micrograms ethinylestradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. Half of the patients taking the new preparation were first-time OC users, the other half switched from another OC. With regard to contraceptive efficacy, the life-table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl-Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in the trial. Dysmenorrhea present in the "switchers" mostly disappeared on the new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behaviour is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favourable effect on dysmenorrhea. The number of clinically diagnosed thrombotic events documented in this study was 0.65 per 1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using non-hormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).. Efficacy, cycle control, tolerance, and adverse events were studied in a clinical phase IV study using a new progestogen, gestodene, in an amount of 75 mcg combined with 30 mcg ethinyl estradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. 1/2 of the patients taking the new preparation were 1st-time OC users, the other 1.2 switched from another OC. With regard to contraceptive efficacy, the life table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in this trial. Dysmenorrhea present in those who switched disappeared for the most part with this new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behavior is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favorable effect on dysmenorrhea. The number of clinically diagnoses thrombotic events documented in this study was 0.65/1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using nonhormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).

Topics: Adult; Blood Pressure; Body Weight; Contraceptives, Oral, Combined; Dose-Response Relationship, Drug; Drug Evaluation; Dysmenorrhea; Ethinyl Estradiol; Female; Humans; Norpregnenes; Ovulation; Thromboembolism

The monophasic combination preparation containing 30 micrograms ethinyl estradiol and 75 micrograms gestodene was tested for contraceptive reliability, cycle control and tolerability in a total of seven phase III clinical studies. A total of 6,854 women were included in these studies, and 69,978 cycles were monitored. Following the commercial introduction of the preparation, further clinical data were obtained with a broader user population. In Germany it was possible to implement an extraordinarily extensive phase IV study in a very short period of time. A total of 523,477 treatment cycles in 95,906 women were included in the analysis. So, for what is probably the first time, a prospective general clinical study for an oral contraceptive was conducted of the same magnitude as the biggest cohort epidemiologic studies. The results of the various phase III and phase IV studies are in close agreement. The combination preparation containing gestodene proved to have high contraceptive reliability and gave excellent cycle control. It was well tolerated and the frequency of adverse reactions was low. To summarize, the monophasic gestodene completely fulfills the demands made of oral contraceptives today.

Topics: Adolescent; Adult; Blood Pressure; Body Weight; Contraceptives, Oral, Combined; Ethinyl Estradiol; Evaluation Studies as Topic; Female; Humans; Menstrual Cycle; Norpregnenes; Thromboembolism

Topics: Adolescent; Contraceptive Agents, Female; Female; France; Humans; Jurisprudence; Norpregnenes; Stroke; Thromboembolism

Oral contraceptives (OC) are a definite risk for venous thrombosis. It is commonly accepted that they cause a fourfold increased risk of thrombosis compared to non-users. The prescription patterns were evaluated from 1990 to 2000 in a northern Italian province (province of Padua). This province is typical of other northern Italian provinces. As a consequence, it can be safely assumed that the observations gathered may apply to the entire north of Italy. During these years, a sharp increase in the use of OC was noted. Furthermore, around 1995 to 1996, a marked switch toward the use of preparations containing third-generation progestins was noted. During the past few years of the observation period, approximately 80% of women use preparations containing third-generation progestins. During the same period, an increased incidence of episodes of venous thromboembolism (VTE) was noted. The increase in the prevalence of VTE episodes appeared to be proportional to the increased use of OC, regardless of the type of progestin contained in the oral contraceptive preparations.

Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Drug Prescriptions; Drug Utilization; Female; Humans; Incidence; Italy; Middle Aged; Norpregnenes; Progesterone Congeners; Risk Factors; Thromboembolism; Thrombophilia; Venous Thrombosis

To estimate the risk of venous thromboembolism among women prescribed the oral contraceptive pill who have acute clinical conditions such as lower limb fractures, compared with women with idiopathic venous thromboembolism.. A nested case-control analysis using the General Practice Research Database, January 1993 to December 1999 was carried out. The participants were women aged 15-39 years, prescribed third generation oral contraceptives (gestodene and desogestrel) or oral contraceptives containing levonorgestrel. The main outcome measures were odds ratios as a measure of the relative risk estimate for venous thromboembolism in women with clinical conditions that predispose to VTE.. The adjusted relative risk estimate for venous thromboembolism among patients with the acute clinical conditions, compared with those without such illness, and adjusted for oral contraceptive use, was 17 (95% CI 6.5, 46).. This paper documents the strong independent association between certain acute clinical conditions and venous thromboembolism in women prescribed oral contraceptives. Failure to accurately identify and exclude such patients from a study of the effect of oral contraceptives on the risk of venous thromboembolism would result in an underestimate of the risk of venous thromboembolism associated with oral contraceptives.

Topics: Adolescent; Adult; Case-Control Studies; Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Levonorgestrel; Norpregnenes; Odds Ratio; Risk Factors; Thromboembolism; Venous Thrombosis

Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Desogestrel; Humans; Levonorgestrel; Norpregnenes; Progesterone Congeners; Risk Factors; Thromboembolism; Venous Thrombosis

Topics: Activated Protein C Resistance; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Norpregnenes; Progesterone Congeners; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism

Recent data indicate that users of third-generation oral contraceptives, those containing the new progestins desogestrel, gestodene, and norgestimate, have 2 to 3 times the risk of venous thromboembolism faced by users of second-generation oral contraceptives. The risk of development of deep vein thrombosis was also found to be 2 to 5 times greater with a low-estrogen, desogestrel-containing oral contraceptive than with second-generation monophasic and triphasic preparations. Investigators point to an acquired resistance to the anticoagulation effects of activated protein C, the most common cause of hereditary thrombophilia, as a possible mechanism. The American College of Obstetrics and Gynecology's Committee on Gynecologic Practice reconfirms the increased risk of venous thromboembolism associated with third-generation progestins versus other progestins. Because the third-generation oral contraceptives may have benefit for some patients, however, it defers to the individual clinician's and patient's judgment regarding the use of a desogestrel-containing formulation (the only third-generation progestin available in the United States).

Topics: Clinical Trials as Topic; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Levonorgestrel; Norpregnenes; Risk Factors; Thromboembolism; Venous Thrombosis

The aim of this study was to assess preferential prescribing of OC according to different thrombotic risk factors.. The control group in an ongoing Danish case-control study on stroke and OCs collected in 1994 and 1995 underwent a control-only analysis concerning the occurrence of thrombotic risk factors among users of different types of OC. Specific attention was given to differences between OCs with second and third generation progestagens. The association between specific risk factors and the pill types was assessed crude and after multivariate analysis with confounder control for age and other risk factors, in order to identify risk factors, which after these corrections still had a significant confounding influence on the prescribing of OC.. Users of OCs with third generation progestagens had a significantly higher proportion of familial thrombotic disposition (23.1%) than users of OCs with second generation progestagens (7.1%) (p = 0.01). After correction for age and other risk factors this difference was still highly significant (p = 0.002). Among users of third generation pills the proportion of short time users (< 1 year) (22.4%) was significantly higher than the per cent among users of OCs with second generation progestagens (5.5%) (p < 0.001). This difference was still significant after correction for age and other risk factors (p < 0.001). Smoking, years of schooling, migraine, and body mass index did not differ significantly between the two pill groups.. In Denmark, women with familial thrombotic disposition are four times more likely being prescribed OCs with third versus second generation progestagens compared with women without such a disposition. At the same time users of OCs with third generation progestagens include significantly more short time users than users of OCs with second generation progestagens. For thrombotic diseases where familial disposition or duration of use of OCs play a role for the pill-associated risk, these differences may significantly influence the thrombotic risk measures in case-control studies and non-randomized cohort studies unless confounder control is conducted for this selection.. An analysis of the occurrence of thrombotic risk factors among users of different types of combined oral contraceptives (OCs) revealed the existence of differential prescribing patterns based on these risk factors. The 206 study participants were among the 1200 controls in a 1994-95 Danish case-control study on stroke and OCs. The 118 users of third-generation OCs containing the progestins desogestrel or gestodene had a significantly higher rate of familial thrombotic disposition (23.1%) than the 56 users of second-generation OCs containing levonorgestrel, norgestrel, and norgestimate (7.1%). Even after adjustment for age and other risk factors, this trend remained significant (p = 0.002). This finding suggests that general practitioners are asking women about thrombotic familial disposition before prescribing OCs and basing the OC type on this information. In addition, there were significantly more short-time users (under 1 year) among users of third-generation OCs (22.4%) than of second-generation OCs (5.5%). This difference also remained significant after adjustment for age and other risk factors (p 0.001). There were no differences between the OC groups in terms of smoking, educational attainment, migraine, and body mass index. Since both thrombotic disposition and duration of OC use may influence the risk of thrombotic diseases, these potential confounders should be controlled in epidemiologic analyses of OC-related thromboembolic risks.

Topics: Adolescent; Adult; Body Mass Index; Case-Control Studies; Causality; Contraceptives, Oral; Denmark; Desogestrel; Dose-Response Relationship, Drug; Female; Humans; Levonorgestrel; Migraine Disorders; Multivariate Analysis; Norgestrel; Norpregnenes; Risk Factors; Smoking; Socioeconomic Factors; Thromboembolism

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

Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Drug Prescriptions; Humans; Norpregnenes; Practice Guidelines as Topic; Risk; Thromboembolism

Topics: Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Norpregnenes; Progesterone Congeners; Thromboembolism; Thrombophlebitis

Topics: Adult; Blood Coagulation Factors; Contraceptives, Oral, Combined; Cross-Sectional Studies; Desogestrel; Female; Fibrinolysis; Humans; Lipids; Middle Aged; Norgestrel; Norpregnenes; Progesterone Congeners; Thromboembolism

A matched case-control study was undertaken in 10 centers in Germany and the United Kingdom to explore the association of current use of major combination oral contraceptives with the occurrence of venous thromboembolism. The cases recruited were 505 women aged 16-44 years with venous thromboembolism, controls were 1877 women (at least 3 controls per case) matched for 5-year age group and region without VTE. The main outcome measures were odds ratios derived by comparing current use of a specific oral contraceptive or group of OC against current use of other groups or against no current use of OC. The odds ratios (95% confidence intervals) for venous thromboembolism were: for third generation products (low dose ethinyloestradiol, gestodene and desogestrel) versus second generation products (low dose ethinyloestradiol, no gestodene and desogestrel, 1.5 (1.1 to 2.0), for third versus second generation products with norgestimate included in third generation, 1.6 (1.2 to 2.2). The odds ratios for current use for women aged 16-44 of specific progestagens versus levonorgestrel-containing compounds were 1.7 (1.1 to 2.6) for gestodene, 1.8 (1.2 to 2.6) for desogestrel, 1.9 (1.0 to 3.6) for norgestimate and 1.3 (0.7 to 2.5) for progestagen-only pills. For women aged 25 to 44 likely to be exposed to any of these progestagens, odds ratios for the comparison of progestagens versus levonorgestrel showed a successive increase by market introduction ranging from 1.5 (0.9 to 2.5) for desogestrel with 30 micrograms oestrogen content (introduced 1981) to 2.8 (1.3 to 6.5) for desogestrel with 20 micrograms oestrogen content (introduced 1992) significant in linear trend analysis (p = 0.00012). The influence of norgestimate classification as third or second generation product does not significantly alter the results regarding the association of third generation products and venous thromboembolism. A direct comparison of current use of norgestimate (which is primarily metabolized to levonorgestrel) versus levonorgestrel shows an increased odds ratio. The trend of increasing risk of progestagens by recency of market introduction when compared with levonorgestrel is strongly indicative of the existence of external bias due to attrition of susceptibles.

Topics: Adolescent; Adult; Bias; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Levonorgestrel; Norgestrel; Norpregnenes; Odds Ratio; Progesterone Congeners; Risk Factors; Thromboembolism

Topics: Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Norpregnenes; Thromboembolism

Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Norpregnenes; Progesterone Congeners; Thromboembolism

Topics: Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Norpregnenes; Progesterone Congeners; Thromboembolism

Several studies suggest an association between the use of third-generation oral contraceptives (OCs) containing either desogestrel or gestodene and an increased risk of venous thromboembolism. Current users of third-generation OCs faced about a two-fold increased risk of thromboembolism than users of other OCs, even after researchers controlled for possible confounding factors that increase the risk for thromboembolism, e.g., smoking. These latest findings suggest that these OCs actually induce the increased risk of thromboembolism. One study showed that body mass index did not account for the added risk of thromboembolism to users of third-generation OCs. Another study found that family history of venous thrombosis did not increase the risk in third-generation OC users. It did find that nulligravidity and the factor V Leiden mutation contributed to the increased risk of venous thromboembolism in third-generation OC users. Health professionals should consider the size of both risks and benefits linked to various OCs when advising women to discontinue or not to begin using third-generation OCs. The increased risk of venous thromboembolism linked to a third generation OC, beyond that linked to the use of an earlier OC, is 10-15/100,000 woman-years of use. Assuming a typical case fatality rate of around 1%, the increased rate of fatal thromboembolism would range from 1 to 1.5/million woman-years. One study found that mortality from vascular diseases among current users of third-generation OCs is essentially the same as that of users of other OCs. No studies have examined any possible benefits from third-generation OC use in terms of incidence and mortality related to myocardial infarction or diabetes mellitus. Women and their health providers need to make their decision by weighing an increase, albeit small, in thromboembolism-related death against a possible decrease in the risk of other serious conditions.

Topics: Contraceptives, Oral; Desogestrel; Female; Humans; Norpregnenes; Risk Factors; Thromboembolism

A multinational hospital-based case-control study of the risk of venous thromboembolic disease associated with combined oral contraceptives (OCs) done in 1989-93 prompted a separate inquiry comparing the risk of venous thromboembolism (VTE) associated with low oestrogen (< 35 micrograms ethinyloestradiol) OCs containing levonorgestrel with risks in low oestrogen preparations containing the third-generation progestagens desogestrel or gestodene. This analysis of data from 9 countries, involved 769 cases and 1979 age matched hospital controls and, in one centre, 246 community controls matched on age and general practice. 137 cases and 203 controls were current users of levonorgestrel (odds ratio [OR with 95% confidence interval] 3.5 [2.6-4.7]), with non-users as the reference; 35 cases and 28 controls were current users of desogestrel (9.1 [4.9-17.0]), and 36 cases and 28 controls were current users of gestodene (9.1 [4.9-16.7]). The ratios of these risks, compared with levonorgestrel, were 2.6 (1.4-4.8) for both products separately. Risk estimates adjusted for body mass index (BMI) were 3.4, 7.3, and 10.2 for levonorgestrel, desogestrel, and gestodene, respectively, compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene, respectively, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls exposed to desogestrel or gestodene were from the UK (Oxford region). In this centre risk estimates compared with non-users, adjusted for BMI, were 2.6, 5.3, and 5.7 for levonorgestrel, desogestrel, and gestodene, respectively. Current users of low oestrogen dose combined OCs containing desogestrel or gestodene appear to be at higher risk of VTE than users of combined OCs containing levonorgestrel. The possibility that these unexpected results on a secondary study objective are due to chance, bias, or residual confounding cannot be excluded entirely and the results need to be confirmed by independent studies. They are at variance with the apparently more favourable metabolic effects of the newer progestagens. Whether the new progestagens are associated with lower risk of arterial disease (stroke and myocardial infarction) must be evaluated further.

Topics: Adult; Age Factors; Body Mass Index; Case-Control Studies; Contraceptives, Oral, Combined; Desogestrel; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Norpregnenes; Progesterone Congeners; Progestins; Risk Factors; Smoking; Thromboembolism; Time Factors

Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.. In two separate studies, researchers analyzed data from the UK General Practice Research Database to compare the cardiovascular risks in healthy women using one of three oral contraceptives (OCs) containing less than 35 mcg estrogen and levonorgestrel, desogestrel, or gestodene. The first study examined unexpected idiopathic cardiovascular deaths; 15 such deaths occurred. The mortality incidence rates were 4.3/100,000 for levonorgestrel OCs, 1.5/100,000 for desogestrel OCs, and 4.8/100,000 for gestodene OCs. When compared with levonorgestrel OCs (the older generation OCs), the relative risk adjusted (ARR) for age and calendar period was 0.4 for desogestrel OCs and 1.4 for gestodene OCs. The second study (cohort and case control analyses) looked at nonfatal venous thromboembolism (VTE). The crude incidence rate for nonfatal VTE was 16.1 for levonorgestrel OCs, 29.3 for desogestrel OCs, and 28.1 for gestodene OCs. When compared with levonorgestrel OCs, the ARR was 1.9 for desogestrel OCs and 1.8 for gestodene OCs. The case control analysis found that use of desogestrel OCs and gestodene OCs increased the risk of developing nonfatal VTE (all cases and controls, ARR = 2.2 and 2.1, respectively). The researchers estimated the excess risk for nonfatal VTE linked to the new generation of OCs to be 16/100,000 woman-years.

Topics: Adult; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Contraceptives, Oral, Combined; Desogestrel; Ethinyl Estradiol; Female; Humans; Incidence; Levonorgestrel; Norpregnenes; Progestins; Risk Factors; Thromboembolism

Topics: Attitude to Health; Australia; Canada; Contraceptives, Oral, Synthetic; Desogestrel; Female; Germany; Humans; Mass Media; Netherlands; Norpregnenes; Norway; Thromboembolism; United Kingdom; United States

Topics: Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Norpregnenes; Thromboembolism