Effects on Hemostasis After Two-Year Use of Low Dose Combined Oral Contraceptives with Gestodene or Levonorgestrel

Abstract

We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera®) or second generation levonorgestrel (Microgynon 30®) combina tion of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were ap parent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fi brinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. En hanced thrombin-antithrombin (TAT)-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 with Micro 30. Increased protein C activity was seen at 3 months and reduced protein 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 levels for 12 months with Gynera and 6 months with Micro 30. De creased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Wil lebrand factor (vWF) were seen in long-term OC use except that β-thromboglobulin (β-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in β-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreat ment levels. Activated protein C resistance (APCR) was nega tive in all subjects before and during OC use. The study indi cated dynamic balance between coagulation and fibrinolysis with no endothelial activation. However, because some hemo static markers showed wide fluctuations during OC use, a longer term study is warranted to investigate any adverse he mostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be less prone to thrombosis. Key Words: Oral contraceptives—Hemostasis.

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