Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel

We studied 67 healthy women who were randomly allocated to receive third ge neration gestodene (Gynera(R)) or second generation levonorgestrel (Microgy non 30(R))combination of low-dose estrogen oral contraceptives (OCs) for th eir hemostatic effects over 2 years. Hemostatic changes were apparent withi n 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb ) concentration decreased by 18 months. Shortened prothrombin time CPT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the Is months of use. Enhanced thrombin-antithrombin (T AT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment (1+2) (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months wit h Micro 30. Increased protein C activity was seen at 3 months and reduced p rotein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer l evels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activ ator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enha nced u-PA activity was only seen in Gynera users. Elevated plasminogen leve ls were apparent throughout both OCs use. PAI-1 levels were significantly d ecreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at LX months and PAI-I antigen at 12 months. No change in platelets an d von Wilebrand factor (vWF) were seen in long-term OC use except that P-th romboglobulin (P-TG) showed decreased trends reaching statistical significa nce by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A f urther significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreatment le vels. Activated protein C resistance (APCR) was negative in all subjects be fore and during OC use. The study indicated dynamic balance between coagula tion and fibrinolysis with no endothelial activation. However, because some hemostatic markers showed wide fluctuations during OC use, a longer term s tudy is warranted to investigate any adverse hemostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be l ess prone to thrombosis.