Effect of oral contraceptives on haemostasis variables.
Combined oral contraceptives (COCs) have effects on a large number of haemostasis variables. We have summarised literature data on effects of COCs containing 30-35 micrograms ethinyl estradiol for the third generation of progestogens (PGs): desogestrel, gestodene and norgestimate. It is concluded that about 15 variables show a shift in distribution of the order of magnitude of their interindividual variation coefficient. When comparing the third generation of PGs with the second one (norgestrel, levonorgestrel) stronger increases are noted for the former for some haemostatic variables. Also differences between desogestrel and gestodene for factor VII were apparent. It indicates that the role of PGs in the effects of COCs is significant and their design may in addition to reduction of oestrogen dosage be important in reducing haemostatic complications. The survey on molecular and cellular mechanisms by which the sex steroids might operate showed a great lack of knowledge. Only for factor XII has a functional oestrogen response element in the DNA definitely been identified. The study of molecular markers of coagulation and fibrinolysis have shown a distinct increased activation of coagulation (F 1 + 2, FPA) and fibrinolysis (PAP), and an increased fibrin turn-over (increased FDPs); platelet products are not found increased (beta TG, PF-4). The increase in fibrinolysis represent a counterforce, but individual changes in variables in coagulation and fibrinolysis do not correlate indicating independent effects and no evidence for a individually regulated balance. A first step in further research might be in understanding the increase in coagulation activation (F 1 + 2) which has so far not been satisfactorily related to changes in blood concentrations of haemostatic factors and possibly local factors.
Kluft
C
C
Gaubius Laboratory, TNO-PG, Leiden, The Netherlands. C.KLUFT@PG.TNO.NL
Lansink
M
M
D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D011372:Progestins / Q000009:adverse effects*
D015415:Biomarkers; D003277:Contraceptives, Oral, Combined; D011372:Progestins; D004997:Ethinyl Estradiol