Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial.
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 randomized 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).
Kemmeren
Jeanet M
JM
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Room D.01.335, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Algra
Ale
A
Meijers
Joost C M
JC
Tans
Guido
G
Bouma
Bonno N
BN
Curvers
Joyce
J
Rosing
Jan
J
Grobbee
Diederick E
DE
D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects; D009154:Mutation; D011486:Protein C / Q000187:drug effects* / Q000378:metabolism; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000235:genetics
D003277:Contraceptives, Oral, Combined; D011486:Protein C; C095381:factor V Leiden; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel; D005165:Factor V