Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a random
From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands; the Department of Neurology and the Department of Haematology, University Medical Center Utrecht, The Netherlands; the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands; and the Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.5ti, http://www.100md.com
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 VLeiden, is still lacking. In a double-blind trial, 51 women without and 35 women with factor VLeiden were randomized to either a second- (30 µg ethinylestradiol/150 µg levonorgestrel) or third- (30 µg ethinylestradiol/150 µg 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 VLeiden. 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 VLeiden. (Blood. 2004;103:927-933)(Jeanet M. Kemmeren Ale Algra, Joost C. M. Meijers Guido Tans Bonno N. Bouma Joyce Curvers Jan Rosing)
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 VLeiden, is still lacking. In a double-blind trial, 51 women without and 35 women with factor VLeiden were randomized to either a second- (30 µg ethinylestradiol/150 µg levonorgestrel) or third- (30 µg ethinylestradiol/150 µg 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 VLeiden. 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 VLeiden. (Blood. 2004;103:927-933)(Jeanet M. Kemmeren Ale Algra, Joost C. M. Meijers Guido Tans Bonno N. Bouma Joyce Curvers Jan Rosing)