gestodene and Cardiovascular-Diseases

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

Progestins have played an important role in hormone replacement therapy (HRT). This article reviews the history, structure, and pharmacology of synthetic progestins, including the new progestins, norgestimate, gestodene, and desogestrel. The benefits and potential effect on carcinoma of the breast for each HRT are summarized. Current treatment alternatives are addressed.

Topics: Breast Neoplasms; Cardiovascular Diseases; Desogestrel; Endometrium; Estrogen Replacement Therapy; Female; Humans; Norgestrel; Norpregnenes; Osteoporosis, Postmenopausal; Progesterone Congeners; Risk Factors; Structure-Activity Relationship

The purpose of the study was to determine the relationship between hemorheological profile, i.e. blood viscosity, and other risk factors for cardiovascular and thrombotic diseases in women taking oral contraceptives and if blood viscosity may be considered a marker of cardiovascular risk in OC users. Plasma levels of coagulation parameters, serum lipids, blood viscosity and RBC deformability were determined in a group of 10 women taking OC vs. 10 controls. The blood parameters were evaluated before OC use and thereafter at 3 and 6 months. A significant change in the partial thromboplastin time, fibrinogen, HDL and apolipoprotein A-I was observed, while the other parameters remained unchanged. Plasma viscosity was significantly increased during OC treatment; whole blood viscosity and RBC deformability remained unchanged. However, although some parameters were significantly modified during OC treatment, all alterations remained within the normal range of laboratory values. The data confirm that low-dose triphasic OC therapy does not affect significantly the coagulation system, serum lipid metabolism and blood viscosity. Plasma viscosity measurement may be considered as a marker for monitoring women using OC because it is apparently the most sensitive parameter.. Previous studies have documented an association between blood viscosity and risk factors for cardiovascular and thromboembolic disease. The present study assessed the impact of use of a low-dose, triphasic oral contraceptive (OC) containing ethinyl estradiol in combination with gestodene on the coagulation system, serum lipid metabolism, and blood viscosity. Enrolled were 10 OC users with no history of OC use before the study and 10 non-users. At 3 and 6 months after initiation of OC use, significant changes were recorded in partial thromboplastin time, fibrinogen, high density lipoprotein, and apolipoprotein A-1. Plasma viscosity was significantly increased during OC use, while whole blood viscosity and erythrocyte deformability remained unchanged. All alterations associated with OC treatment remained within the normal range of laboratory values, however. Thus, these findings suggest an absence of any significant OC effects on the hemostatic balance or lipid metabolism that might represent a risk factor for cardiovascular disease. Moreover, the measurement of blood viscosity may be a promising marker for monitoring thrombotic risk in women taking OCs given its apparent high sensitivity.

Topics: Adolescent; Adult; Blood Coagulation; Blood Viscosity; Cardiovascular Diseases; Contraceptives, Oral, Combined; Erythrocyte Deformability; Ethinyl Estradiol; Female; Humans; Lipids; Norpregnenes; Regression Analysis; Risk Factors

This study aimed to evaluate the associated cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills (COCPs) via determination of lipids profiles, Castelli index I, leptin, adiponectin, and resistin concentrations as cardiovascular risk factors. In this cross-sectional study, the study groups consisted of control group that represented by 30 healthy married women who were not on any contraceptive mean or any hormonal therapy and had normal menstrual cycles, group two consisted of 30 women who were users of Levonorgesterl 0.15 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, group three consisted of 30 women who were users of Gestodene 0.075 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, and group four consisted of 30 women who were users of Drospirenone 3 mg plus Ethinylestradiol 0.03 mg as 21 days cycle. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. P value <0.05 was considered to be significant. The comparison of the studied groups revealed that COCPs containing levonorgestrel plus ethinylestradiol resulted in significantly lower adiponectin level, and significantly higher leptin and resistin levels with more atherogenic lipid profile presented by significantly higher LDL-C, significantly lower HDL-C concentrations, and significantly higher atherogenic index. Formulation containing ethinylestradiol combined with gestodene neither altered adipose tissue function nor showed deleterious effect on lipid panel. Formulation containing ethinylestradiol combined with drospirenone resulted in significantly higher HDL-C and adiponectin concentrations. In conclusion, the uptake of COCPs containing levonorgestrel plus ethinylestradiol is associated with high cardiovascular risk since this formulation showed significantly lower adiponectin concentration, significantly higher leptin, resistin, and atherogenic index as compared to other studied groups. By contrast, the formulations containing ethinylestradiol combined with third generation progestin gestodene or fourth generation progestin drospirenone are associated with low cardiovascular risk since they neither altered adipose tissue function nor impaired lipoprotein metabolism as experienced by their favorable effect on leptin, adiponectin, and resistin, with non-changed atherogenic index, higher HDL-C levels and lower LDL-C levels as compared to levonorgestrel plus ethinylestradiol formulation.

Topics: Adiponectin; Adipose Tissue; Adult; Androstenes; Anthropometry; Cardiovascular Diseases; Chemistry, Pharmaceutical; Cholesterol, HDL; Cholesterol, LDL; Contraceptives, Oral, Combined; Cross-Sectional Studies; Drug Combinations; Egypt; Ethinyl Estradiol; Female; Humans; Leptin; Levonorgestrel; Norpregnenes; Resistin; Risk Factors

This study examined the association between estrogen receptor α gene (ESR1) polymorphisms and blood pressure (BP), heart rate (HR) and autonomic modulation of HR in a sample population.. Two hundred thirty-two young healthy women were selected, and those using oral contraceptives (OC) were compared with nonusers (control group). Short-term HR variability (HRV) was evaluated in both the supine and sitting positions using temporal indices rMSSD [square root of the mean squared differences of successive R-R intervals (RRi) divided by the number of RRi minus one], SDNN (root mean square of differences from mean RRi, divided by the number of RRi) and frequency domain methods. Power spectral components were reported at low frequency (LF) and high frequency (HF) and as LF/HF ratio. ESR1 c.454-397T>C (rs2234693) and c.454-351A>G (rs9340799) polymorphisms were determined by polymerase chain reaction and fragment restriction analysis.. The ESR1 T>C and A>G polymorphisms had no effect on HR, rMSSD, SDNN, LF, HF or LF/HF ratio (supine or sitting), independently of OC use. The ESR1 T-A, T-G, C-A and C-G haplotypes were not associated with HR, BP or HRV.. ESR1 variants had no effect on the autonomic modulation of HR in young women users and nonusers of OC and may not be implicated in cardiovascular risk in young women.

Topics: Adult; Autonomic Nervous System; Blood Pressure; Brazil; Cardiovascular Diseases; Contraceptives, Oral, Combined; Desogestrel; Estrogen Receptor alpha; Estrogens; Ethinyl Estradiol; Female; Genetic Association Studies; Heart Rate; Humans; Introns; Levonorgestrel; Norpregnenes; Polymorphism, Single Nucleotide; Progestins; Risk Factors

Topics: Adolescent; Adult; Cardiovascular Diseases; Case-Control Studies; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Europe; Female; History, 20th Century; Humans; Multicenter Studies as Topic; Norpregnenes; Risk; Young Adult

To analyze the relationship between third generation oral contraceptive (OC) use and various cardiovascular risk factors--including markers of inflammation--in a population-based sample.. Data on OC use were obtained from women, aged 25-44 years participating in the MONICA Augsburg survey 1994-1995. Complete data were available from 841 women. Third generation OCs were defined as OCs containing desogestrel or gestodene, the remaining OC products were summarized in the group "other OC.". Women taking third generation OCs had significantly higher C-reactive protein, fibrinogen, plasma viscosity, and HDL-cholesterol concentrations compared to the "other OC" group and non-users. In contrast, LDL-cholesterol was identical in the three groups. The analyses of interaction between smoking and OC use revealed that smoking women taking third generation pills had a less favourable pattern concerning inflammatory markers compared to women not on OC or using other products.. Potentially harmful effects of OCs may arise from their positive association with the acute phase response. There is a close relationship with inflammatory markers in particular in women taking third generation OCs, which may, at least in part, contribute to the increased atherothrombotic risk, reported specifically in these women.

Topics: Adult; Blood Viscosity; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Contraceptives, Oral, Synthetic; Desogestrel; Female; Fibrinogen; Humans; Norpregnenes; Risk Factors; Smoking

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

The European Society of Contraception developed a survey to examine birth control methods in the 12 countries++ of the European Community. Responses to those questions relating to prescribing++ practices of oral contraceptives (OCs) are presented herein. The survey was sent to 400 physicians. One hundred two responded, most from France, Belgium, and the United Kingdom. The responses revealed that the most popular OCs are modern combined formulations containing low doses of ethinyl estradiol and progestogens such as norgestimate, desogestrel, gestodene, and levonorgestrel. More than half of physicians prescribe a particular formulation because of its tolerability and 20% because of its hormonal content. More than 90% prescribe OCs to healthy, nonsmoking women over 40. However, three fourths will not prescribe OCs to smokers over 35. Half of physicians recommend mammography for their older OC patients. Half also recommend cholesterol screening, but 8% only for women over 30. Most physicians are no longer reluctant to prescribe OCs to their diabetic patients: 61% prescribe OCs for women with non-insulin-dependent diabetes, 56% for those with insulin-dependent diabetes, and 85% for those with a history of gestational diabetes. Despite recent studies showing no relation between past OC use and cardiovascular disease, 42% of physicians said that their greatest OC-related health concern is cardiovascular disease. One third cited noncompliance as their greatest concern. These results reveal inhomogeneous prescribing practices for OCs among European physicians. ¿Over-screening¿--not prescribing the pill because of perceived (but not necessarily real) health risks--may be depriving many women of the contraceptive and noncontraceptive benefits of OCs. Complete and accurate information--as promoted by the European Society of Contraception--is one way to combat such overscreening.. Findings are presented from the 1993 European Society of Contraception Oral Contraceptive Survey conducted in 12 member countries among 102 physicians. Findings are considered suggestive because of the low response rate of 25% to the mailed questionnaire to 400 physicians. The aim is to determine the prescribing practices of oral contraceptives. Over 50% of physicians prescribed the following modern, low-dose combined formulations: Marvelon, Mercilon, Minulet, Gynera, Cilest, and Femodene. 66% of physicians prescribed monophasic pills containing 20-30 mcg of ethinyl estradiol and low doses of desogestrel, gestodene, levonorgestrel, or norgestimate. 58% preferred oral pills because of their tolerability. Other desirable features were the cost, hormonal content, and other factors. 94% prescribed oral pills for women aged over 40 years who were healthy and did not smoke. 75% would not prescribe oral pills to women who were over the age of 35 years and who smoked. Over 50% of physicians recommended mammograms for women aged over 35 years who used oral pills. 45% routinely performed lipoprotein screening of oral pill users. 8% did so only for patients aged over 30 years. 42 physicians out of the 102 responding had a protocol based on the total cholesterol level. 61% prescribed oral pills for women with non-insulin-dependent diabetes. The majority prescribed oral pills for women with insulin-dependent diabetes. 38% of physicians who prescribed oral pills for women with diabetes prescribed very-low-dose monophasic oral contraceptives. 85% prescribed oral pills for women with gestational diabetes. 42% were concerned about patient risk of cardiovascular disease. The study revealed a range of practices among physicians.

Topics: Adult; Aging; Cardiovascular Diseases; Contraception; Contraceptives, Oral; Data Collection; Desogestrel; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Estradiol Congeners; Ethinyl Estradiol; Europe; Female; Humans; Levonorgestrel; Norgestrel; Norpregnenes; Progesterone; Progesterone Congeners; Risk Factors; Smoking; Surveys and Questionnaires