Comparative studies of 30 μg ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets

Daly, L.; Bonnar, J.

doi:10.1016/0002-9378(90)90596-y

Cited by 74 publications

(27 citation statements)

References 14 publications

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“…The effects of these OCs on platelets and hemostasis have been evaluated in various comparative clinical studies including OCs containing LNG and/or gestodene (GSD) for up to 12 cycles of treatment. In these studies, statistically significant changes in platelet count have not been reported with DSGcontaining OCs [13][14][15]. In addition, little effect on coagulation and fibrinolytic factors was found, and the occasionally reported changes were slight, remained within the normal range, were similar to those observed with LNG-and GSDcontaining OCs and were parallel to earlier reports in the literature.…”

Section: Discussionsupporting

confidence: 84%

The effects of two phasic oral contraceptives on hemostasis and platelet function

et al. 1995

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Objective." To compare the effects on hemostatic parameters of a combiphasic oral contraceptive containing desogestrel and ethinyl estradiol (DSG/EE) and a triphasic oral contraceptive containing levonorgestrel and ethinyl estradiol (LNG/EE). Methods:In an open-label, randomized, group-comparative study in 10 healthy volunteers per treatment group, the effects on parameters of coagulation, anticoagulafion, fibrinolysis, anfifibrinolysis and platelet function were determined at baseline, after three treatment cycles, and after a post-treatment cycle. Changes from baseline were analyzed using a paired t-test, whereas betweengroup differences were analyzed by means of an analysis of co-variance.Results: Both OC preparations induced modest changes of some coagulation, anticoagulation, fibrinolysis and antifibrinolysis parameters, although all mean values remained within the normal range. No significant effects were observed with either OC with respect to platelet function. Statistically significant differences between the two preparations could occasionally be observed: the concentrations of anfithrombin III (AT-III) and Factor VII were higher with the DSG/EE preparation than with the LNG/EE preparation at the end of treatment and AT-III activity, AT-III concentration, Factor X concentration, and plasminogen activity were higher with DSG/EE than with LNG/EE in the post-treatment cycle.Conclusions: Combiphasic DSG/EE and triphasic LNG/EE, both OCs with a comparable amount of EE per cycle, had no clinically significant effect on the overall hemostatic balance. 228Weinges et al.

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Section: Discussionsupporting

confidence: 84%

The effects of two phasic oral contraceptives on hemostasis and platelet function

et al. 1995

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“…The levels of FVII and the concentrations of lipids in this study are consistent with those described in other reports of women on low-dose or sequential OC pills. In fact, the increase noted in FVII levels represents a well-documented effect of OCs, 14,[25][26][27][28][29][30][31] as does that of chol, TGs, HDL-chol, and apoA1 levels. 32,59 -62 Most of the studies 14,28,[61][62][63] and a recent review 31 have described an increase in FVIIc and FVIIAg levels that was roughly related to the estrogen dose.…”

Section: Discussionmentioning

confidence: 99%

“…19 -22 The effect of OCs on hemostatis is an increase in the levels of some coagulation factors (factors II, VII [FVII], IX, X, XI, and VIII; von Willebrand factor; and fibrinogen), of protein C, and of protein complexes and fragments related to the activation of coagulation (thrombin-antithrombin complexes and D-dimer); these enhance fibrinolysis and decrease the levels of antithrombin III, protein S, and C4b-binding protein. [23][24][25][26][27][28][29][30][31] Concerning FVII, a relationship between FVII levels, the dose of estrogen, [23][24][25][26][27][28]31 and progestogen (norethisterone but not D-norgestrel 32 ) was consistently found. It is difficult, though, to pinpoint whether these changes are due to the estrogen or the progestative compound, and it is still a matter of debate whether the excess CVD risk after the use of OCs is related to the resulting dyslipidemia, the hemostasis changes, or both.…”

mentioning

confidence: 99%

Oral Contraceptives Highlight the Genotype-Specific Association Between Serum Phospholipids and Activated Factor VII

Mariani

Conard

Bernardi

et al. 1999

ATVB

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Abstract-The present analysis was undertaken to study the effect of oral contraceptive (OC) use on activated factor VII (FVIIa) in subjects characterized by FVII genotypes, with the further aim of evaluating the role of lipids in this pharmacological interaction. In OC users (nϭ42) and nonusers (nϭ130) Key Words: factor VII Ⅲ activated factor VII Ⅲ phospholipids Ⅲ factor VII genotype S ince the introduction of oral contraceptives (OCs) in the 1960s, epidemiological studies have revealed an association between their use and an increase in the risk of cardiovascular disease (CVD). [1][2][3][4][5][6] The most important cardiovascular complications noted were venous thromboembolism, myocardial infarction, and thrombotic stroke, 6 -11 with higher risk and susceptibility in female smokers in the 35ϩ age range. 12 The increased CVD risk has been attributed to the estrogenic component 7,13 : in fact, it was found to be reduced after the introduction of OCs containing a lower estrogen dose, [13][14][15][16][17][18] but recently venous thromboembolism was found to be higher in women using contraceptives containing third-generation compared with second-generation progestogens. 19 -22 The effect of OCs on hemostatis is an increase in the levels of some coagulation factors (factors II, VII [FVII], IX, X, XI, and VIII; von Willebrand factor; and fibrinogen), of protein C, and of protein complexes and fragments related to the activation of coagulation (thrombin-antithrombin complexes and D-dimer); these enhance fibrinolysis and decrease the levels of antithrombin III, protein S, and C4b-binding protein. [23][24][25][26][27][28][29][30][31] Concerning FVII, a relationship between FVII levels, the dose of estrogen, [23][24][25][26][27][28]31 and progestogen (norethisterone but not D-norgestrel 32 ) was consistently found. It is difficult, though, to pinpoint whether these changes are due to the estrogen or the progestative compound, and it is still a matter of debate whether the excess CVD risk after the use of OCs is related to the resulting dyslipidemia, the hemostasis changes, or both. Recently, a meta-analysis 33 pointed out the absence of an association between the duration of OC administration and CVD risk; the same analysis showed that the increased risk was limited to the period of OC administration.Because FVII has attracted attention owing to its association with lipids (namely triglycerides [TGs] and cholesterol

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“…Results of comparative studies using 30 /zg of ethinyl estradiol combined with either gestodene or desogestrel indicate that serum plasminogen levels and fibrinolytic activity increased with use of these preparations; moreover, the enhancement of fibrinolysis most likely counteracts the increase in fibrinogen and coagulation activity and protects the dynamic balance between these two systems. In addition, no clinically significant difference in risk of thrombotic events has been observed with use of either gestodene or desogestrel [6,8].…”

Section: Coagulationmentioning

confidence: 99%

Noncontraceptive benefits of modern low-dose oral contraceptives

Thorneycroft

1992

Adv Contracept

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Most oral contraceptive formulations in current use contain 50 micrograms or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5-1 mg), norgestrel (0.3-0.5 mg), or levonorgestrel (0.05-0.25 mg) [1]. The new generation of progestins--norgestimate, desogestrel and gestodene--are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins. Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2]. For the new formulations containing less than 50 micrograms of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent noncontraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance.

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Comparative studies of 30 μg ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets

Cited by 74 publications

References 14 publications

The effects of two phasic oral contraceptives on hemostasis and platelet function

The effects of two phasic oral contraceptives on hemostasis and platelet function

Oral Contraceptives Highlight the Genotype-Specific Association Between Serum Phospholipids and Activated Factor VII

Noncontraceptive benefits of modern low-dose oral contraceptives

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