***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: A plausible mechanism to explain thrombotic risk differences associated with the use of second- and third-generation oral contraceptives ( OCs ) , particularly in carriers of factor V(Leiden ) , is still lacking . In a double-blind trial , 51 women without and 35 women with factor V(Leiden ) were r and omized to either a second- ( 30 microg ethinylestradiol/150 microg levonorgestrel ) or third- ( 30 microg ethinylestradiol/150 microg desogestrel ) generation OC . After 2 cycles of use and a wash-out of 2 cycles , the participants continued with the corresponding progestagen-only preparation .  Hemostatic variables that probe the activity of the anticoagulant protein C system were determined . Compared with levonorgestrel , desogestrel-containing OCs significantly decreased protein S and increased activated protein C ( APC ) resistance in both groups . OCs with desogestrel had the most pronounced effects in carriers of factor V(Leiden ) . Progestagen-only preparations caused changes of anticoagulant parameters opposite to those of combined OCs , which in a number of cases were more pronounced with levonorgestrel . Our data show that progestagens in combined OCs counteract the thrombotic effect of the estrogen component . The higher thrombotic risk associated with third-generation OCs compared with second-generation OCs may be explained by the fact that desogestrel appeared less antithrombotic than levonorgestrel , especially in women with factor V(Leiden ) BACKGROUND Current use of oral contraceptives ( OCs ) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism ( PE ) . Little is known about residual effects of past OC use . Furthermore , few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease . METHODS In this prospect i ve study information was obtained through question naires sent every 2 years ( 1976 - 92 ) to 1125,93 women aged 30 - 55 in 1976 . We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period . FINDINGS From self-reports and medical records , we documented 123 cases of primary PE ( no identified antecedent cancer , trauma , surgery , or immobilisation ) . Current users of postmenopausal hormones had an increased risk of primary PE ( relative risk adjusted for multiple risk factors 2.1 [ 95 % CI 1.2 - 3.8 ] ) . However , past use showed no relation to PE ( 1.3 [ 0.7 - 2.4 ] ) . In current users of OCs the risk of primary PE was about twice that in non-users ( 2.2 [ 0.8 - 5.9 ] ) , but this finding was based on only five cases who were current OC users . Users of OCs in the past had no increase in risk of PE ( 0.8 [ 0.5 - 1.2 ] ) . These relations were consistent irrespective of cigarette-smoking status . INTERPRETATION Primary PE was uncommon in this cohort . The risk was increased by current though not past use of postmenopausal hormones or OCs The objective of this study was to assess the influence of oral contraceptives ( OCs ) on the risk of venous thromboembolism ( VTE ) in young women . A 5-year case-control study including all Danish hospitals was conducted . All women 15 - 44 years old , suffering a first ever deep venous thrombosis or a first pulmonary embolism ( PE ) during the period January 1 , 1994 , to December 30 , 1998 , were included . Controls were selected annually , 600 per year in 1994 - 1995 and 1200 per year 1996 - 1998 . Response rates for cases and controls were 87.2 % and 89.7 % , respectively . After exclusion of nonvalid diagnoses , pregnant women , and women with previous thrombotic disease , 987 cases and 4054 controls were available for analysis . A multivariate , matched analysis was performed . Controls were matched to cases within 1-year age b and s. Adjustment was made for confounding influence ( if any ) from the following variables : age , year , body mass index , length of OC use , family history of VTE , cerebral thrombosis or myocardial infa rct ion , coagulopathies , diabetes , years of schooling , and previous birth . The risk of VTE among current users of OCs was primarily influenced by duration of use , with significantly decreasing odds ratios ( OR ) over time : < 1 year , 7.0 ( 5.1 - 9.6 ) ; 1 - 5 years , 3.6 ( 2.7 - 4.8 ) ; and > 5 years , 3.1 ( 2.5 - 3.8 ) , all compared with nonusers of OCs . After adjustment for confounders , current use of OCs with second- ( levonorgestrel or norgestimate ) and third- ( desogestrel or gestodene ) generation progestins when compared with nonuse result ed in ORs for VTE of 2.9 ( 2.2 - 3.8 ) and 4.0 ( 3.2 - 4.9 ) , respectively . After adjusting for progestin types and length of use , the risk decreased significantly with decreasing estrogen dose . With 30 - 40 microg as reference , 20 and 50 microg products implied ORs of 0.6 ( 0.4 - 0.9 ) and 1.6 ( 0.9 - 2.8 ) , respectively ( p(trend ) = 0.02 ) . After correction for duration of use and differences in estrogen dose , the third/second-generation risk ratio was 1.3 ( 1.0 - 1.8 ; p < 0.05 ) . In conclusion , use of OCs was associated significantly to the risk of VTE . The risk among current users was reduced by more than 50 % during the first years of use . The risk increased more than 100 % with increasing estrogen dose , and the difference in risk between users of third- and second-generation OCs , after correction for length of use and estrogen dose , was 33 % Third-generation oral contraceptives ( OC ) have been associated with an increased risk of venous thrombosis compared with second-generation OC . To find an explanation for this increased risk , the effect of a second- and third-generation OC and of the progestagens used in these pills on several fibrinolytic parameters was studied in the absence or presence of the factor V Leiden mutation . In a single-center , double-blind trial , 51 women without and 35 women with the factor V Leiden mutation were r and omized to either a second-generation ( 30 μg ethinylestradiol/150 μg levonorgestrel ) or a third-generation ( 30 μg ethinylestradiol/150 μg desogestrel ) oral contraceptive . After two menstrual cycles of use and a wash-out period of two cycles , the participants received the corresponding progestagen-only preparation containing 150 μg levonorgestrel or 150 μg desogestrel . D-Dimers , thrombin-activatable fibrinolysis inhibitor ( TAFI ) and the clot lysis time in the absence ( LYSmin ) or the presence ( LYSplus ) of a blocking anti-factor XI antibody were determined in plasmas of the participating women , and the mean difference in changes between the OC were calculated . Both combined OC induced increased plasma levels of D-dimers and TAFI , and induced a prolongation of LYSplus , whereas LYSmin hardly changed . Virtually no changes in fibrinolytic parameters were observed for the progestagen-only preparations . No differential effects between levonorgestrel- and desogestrel-containing OC were found in women without factor V Leiden . Women with the mutation on levonorgestrel-containing OC showed an increased LYSplus compared with desogestrel containing OC ( 3.9 ; 95 % confidence interval , 0.1–7.7 ) . When using progestagen-only preparations , no differential effect on the fibrinolytic parameters were found , except for non-carriers on levonorgestrel who showed a reduced LYSmin compared with non-carriers on desogestrel ( −4.0 ; 95 % confidence interval , −7.8 to −0.2 ) . In conclusion , the effect of oral contraceptives on fibrinolytic parameters is largely independent of the type of progestagen . The increased fibrinolytic activity during OC use appears to be induced by the estrogen component and may be counteracted by increased TAFI activation . This may result in an enhanced downregulation of fibrinolysis Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone  , relative to current users of preparations containing levonorgestrel .  Design Nested case-control study . Setting UK General Practice Research Data base . Participants Women aged 15 - 44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009 . Cases were women with a first diagnosis of venous thromboembolism ; up to four controls , matched by age , duration of recorded information , and general practice , were r and omly selected for each case . Main outcome measures Odds ratios and 95 % confidence intervals estimated with conditional logistic regression ; age adjusted incidence rate ratio estimated with Poisson regression . Results 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified . In the case-control analysis , current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use ; the odds ratio adjusted for body mass index was 3.3 ( 95 % confidence interval 1.4 to 7.6 ) . Subanalyses suggested that referral , diagnostic , first time user , duration of use , and switching biases were unlikely explanations for this finding . The crude incidence rate was 23.0 ( 95 % confidence interval 13.4 to 36.9 ) per 100 000 woman years in current users of drospirenone and 9.1 ( 6.6 to 12.2 ) per 100 000 woman years in current users of levonorgestrel oral contraceptives . The age adjusted incidence rate ratio was 2.7 ( 1.5 to 4.7 ) . Conclusions These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel OBJECTIVE This study aim ed to compare the effects on hemostasis variables of a contraceptive vaginal ring with those of an oral contraceptive . STUDY DESIGN Twenty-three and 22 healthy premenopausal women were  r and omized to the contraceptive vaginal ring ( 150 microg Nestorone and 15 microg ethinyl estradiol ) or Stediril 30 during 3 cycles . Analysis of covariance was performed with baseline values as covariate . RESULTS The contraceptive vaginal ring changed most hemostasis variables similarly but raised ( 95 % confidence intervals of percent treatment differences ) Factor VIIt ( 28 % to 49 % ) , extrinsic activated protein C resistance ( 14 % to 65 % ) , and sex hormone-binding globulin ( 117 % to 210 % ) and lowered Protein S ( -32 % to -16 % ) and the global activated partial thromboplastin time-based activated protein C resistance ( -12 % to -2 % ) more than the oral contraceptive . CONCLUSION The contraceptive vaginal ring affected some measured hemostasis variables and sex hormone-binding globulin differently from the oral contraceptive , most likely because of difference in and rogenicity of the progestins . The results suggest that the contraindications for oral contraceptive use would also apply to the tested contraceptive vaginal ring Compared to second generation , the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis  especially in women with the factor V Leiden mutation . To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation . In a single center , double blind trial , 51 women without and 35 women with the factor V Leiden mutation were r and omized to either a second generation ( 30 microg ethinylestradiol/150 microg levonorgestrel ) or a third generation ( 30 microg ethinylestradiol/150 microg desogestrel ) oral contraceptive . After two cycles of use and a wash-out period of 2 menstrual cycles , the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel . In plasmas of the participating women fragment 1 + 2 , factor V , VII , VIII , IX , X and XI were determined . Both combined oral contraceptives induced a decrease in factor V , whereas the levels of all other coagulant parameters increased . However , 
    Output:
    
All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis .
The effect size depended both on the progestogen used and the dose of ethinylestradiol .