Abstract
This is the first double-blind, controlled, randomized study comparing the effect
of different estrogen components in oral contraceptives (OCs) on hemostasis variables.
Four groups of 25 women each were treated for six cycles with monophasic combinations
containing 21 tablets with either 30 μg ethinylestradiol (EE) + 2 mg dienogest (DNG)
(30EE/DNG), 20 μg EE + 2 mg DNG (20EE/DNG), 10 μg EE + 2 mg estradiol valerate (EV)
+ 2 mg DNG (EE/EV/DNG) or 20 μg EE + 100 μg levonorgestrel (LNG) (EE/LNG). Blood samples
were taken on Days 21–26 of the control cycle and on Days 18–21 of the first, third
and sixth treatment cycle. Treatment with all four OCs caused an increase in levels
of fibrinogen, prothrombin fragment 1+2, D-dimer, plasminogen, plasmin-antiplasmin
complex and an increase in protein C activity, a decrease in antithrombin activity,
tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), and
a slight decrease in the sensitivity to activated protein C, but no significant change
in that of the thrombin-antithrombin complex. In users of the DNG-containing OCs,
the reduction in total and free protein S, and in t-PA and PAI was dependent on the
EE dose, while factor VII activity was elevated, but not significantly different from
EE/LNG. The results are in agreement with those of previous studies. The effects of
EE/EV/DNG on total and free protein S and on t-PA and PAI were lower than those of
20EE/DNG, suggesting that the impact of 2 mg EV on several hemostasis variables is
less than that of 10 μg EE. The results show an antagonistic effect of LNG on the
EE-induced rise of factor VII activity and fragment 1+2 and on the EE-dependent reduction
of total and free protein S.
Keywords
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Article info
Publication history
Accepted:
March 11,
2004
Received in revised form:
March 11,
2004
Received:
December 30,
2003
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
