A comparison of the effects of two triphasic oral contraceptives on haemostasis

Abstract

The effects of two cyclically administered, triphasic, combined low dosage oestrogen and progestogen oral contraceptives on haemostasis have been compared in a longitudinal study, over 6 months, in 26 healthy females aged 16-30 years. Subjects received either Logynon (ethinyl oestradiol and Levonorgestrol, n = 14) or SHD 415G (Schering U.K., n = 12), which contains a similar dosage of ethinyl oestradiol, but in combination with a new progestogen, gestodene. Both groups showed increases in biological activities of procoagulant factors fibrinogen, X and XII and decreased activity of the naturally occurring coagulation inhibitor antithrombin III (AT-III). The majority of these changes were statistically significant (P less than 0.05 to less than 0.001), apparent after one cycle and maintained over the six cycle period. FVII activity increased in both groups, achieving statistical significance (P less than 0.01) by cycle 6 in the SHD 415G group but not in the females receiving Logynon. Protein C activity remained unchanged in both groups. Between-group comparisons showed no differences in the procoagulant factor changes, but protein C was lower (P less than 0.05) in the SHD 415G group after three cycles of therapy. These findings indicate that both triphasic oral contraceptives Logynon and SHD 415G induce increases in procoagulant factor activities which are not balanced by increased biological levels of the two most important physiological coagulation inhibitors AT-III and protein C. These prothrombotic changes are not modified by the new progestogen, gestodene.

The effect of oestrogen dose and progestogen type on haemostatic changes in women taking low dose oral contraceptives

“…In contrast, Basdevant et al 22 found a decrease in antithrombin III antigen activity in women using a 30 μg EE/DES combination but not in women using a 20 μg EE/DES combination. Antigenic protein C levels have been shown to be increased, but studies of protein C activity suggest that functional protein C is unaffected by oestrogen/progestogen combinations 23–25 .…”

Guidelines on the investigation and management of thrombophilia. The British Committee for Standards in Haematology.

“…Antithrombin III levels are in the normal range in normal pregnancy.4' Oral contraceptives cause a reduction in total and free PS levels,42 a reduction in ATIII levels, but no change in PC activity. 43 Wherever possible results should be confirmed when the patient is neither pregnant nor taking oral contraceptives.…”

Oral Contraceptives, Hormone Replacement Therapy and Haemostasis

“…Few studies have compared the haemostasis changes of different progestogens combined with the same dose of ethinyl estradiol. No clear difference in levels of fibrinogen and coagulation factors II, VIII or X, or anti‐thrombin and fibrinolytic activity has been observed (32–36). However, a tendency to lower levels of anti‐thrombin and higher levels of coagulation factors was seen with the third generation progestogens (Table 4).…”