Effects of combined oral contraceptives (OCs) and progestagen-only preparations on anticoagulant parameters in the absence or presence of the factor VLeidenmutation
. | Levonorgestrel-containing OC . | . | Desogestrel-containing OC . | . | Mean difference in change (95% CI) . | Levonorgestrel only . | . | Desogestrel only . | . | Mean difference in change (95% CI)‡ . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | No use, mean ± SD . | OC use, mean ± SD . | No use, mean ± SD . | OC use, mean ± SD . | . | No use,†mean ± SD . | OC use, mean ± SD . | No use, mean ± SD . | OC use, mean ± SD . | . | ||||
| Factor VLeiden-negative | ||||||||||||||
| Protein C | 96.0 ± 18.3 | 108.8 ± 21.7 | 92.0 ± 14.0 | 103.7 ± 17.8 | −1.1 (−7.2 to 5.0) | 96.7 ± 18.3 | 92.7 ± 18.6 | 92.0 ± 14.0 | 84.9 ± 11.5 | −3.1 (−6.8 to 0.6) | ||||
| Protein S total | 88.5 ± 13.2 | 83.4 ± 13.6 | 85.9 ± 9.9 | 71.7 ± 10.2 | − 9.1 (−13.4 to −4.7) | 88.6 ± 13.4 | 94.9 ± 13.4 | 85.9 ± 9.9 | 92.5 ± 13.2 | 0.3 (−4.2 to 4.7) | ||||
| Protein S free | 39.9 ± 7.0 | 43.9 ± 8.0 | 38.9 ± 5.8 | 33.8 ± 7.5 | −9.2 (−12.0 to −6.4) | 40.0 ± 7.1 | 47.9 ± 8.4 | 38.9 ± 5.8 | 42.7 ± 7.1 | −4.0 (−6.4 to −1.7) | ||||
| C4BP | 89.9 ± 20.1 | 77.1 ± 17.3 | 88.8 ± 15.8 | 79.1 ± 15.1 | 2.6 (−1.5 to 6.6) | 89.2 ± 20.3 | 82.0 ± 15.8 | 88.8 ± 15.8 | 87.5 ± 17.8 | 6.0 (0.03 to 12.0) | ||||
| PSAPCind | 1.32 ± 0.12 | 1.19 ± 0.08 | 1.34 ± 0.13 | 1.14 ± 0.07 | −0.08 (−0.13 to −0.02) | 1.32 ± 0.12 | 1.46 ± 0.23 | 1.34 ± 0.13 | 1.35 ± 0.13 | −0.13 (−0.20 to −0.06) | ||||
| PCI | 90.6 ± 16.6 | 101.0 ± 15.0 | 90.5 ± 13.7 | 99.5 ± 18.1 | −1.4 (−8.4 to 5.6) | 88.9 ± 14.6 | 90.4 ± 17.7 | 90.5 ± 13.7 | 90.0 ± 14.4 | −2.0 (−7.8 to 3.9) | ||||
| APC-sr | 1.92 ± 0.61 | 3.26 ± 0.72 | 2.04 ± 0.63 | 3.76 ± 0.77 | 0.38 (0.08 to 0.67) | 1.93 ± 0.63 | 1.58 ± 0.61 | 2.04 ± 0.63 | 1.80 ± 0.52 | 0.11 (−0.09 to 0.30) | ||||
| Factor VLeiden-positive | ||||||||||||||
| Protein C | 92.1 ± 12.3 | 102.5 ± 16.3 | 106.6 ± 15.9 | 122.7 ± 22.2 | 5.7 (−1.8 to 13.3) | 92.1 ± 12.3 | 86.2 ± 11.1 | 106.6 ± 15.9 | 96.5 ± 14.9 | −4.2 (−9.0 to 0.7) | ||||
| Protein S total | 88.2 ± 11.4 | 85.9 ± 12.9 | 96.9 ± 10.9 | 77.6 ± 11.1 | −16.9 (−23.8 to −10.1) | 88.2 ± 11.4 | 95.2 ± 10.5 | 96.9 ± 10.9 | 100.6 ± 11.2 | −3.2 (−8.1 to 1.6) | ||||
| Protein S free | 42.2 ± 9.4 | 45.9 ± 9.9 | 42.1 ± 8.1 | 35.3 ± 8.4 | −10.5 (−15.0 to − 5.9) | 42.2 ± 9.4 | 48.9 ± 7.8 | 42.1 ± 8.1 | 45.9 ± 6.8 | −2.9 (−5.9 to 0.1) | ||||
| C4BP | 80.5 ± 11.2 | 72.3 ± 9.8 | 101.5 ± 12.7 | 85.4 ± 16.6 | −8.0 (−13.9 to −2.1) | 80.5 ± 11.2 | 75.1 ± 9.7 | 101.5 ± 12.7 | 95.3 ± 12.1 | −0.8 (−6.4 to 4.9) | ||||
| PSAPCind | 1.24 ± 0.10 | 1.16 ± 0.10 | 1.33 ± 0.12 | 1.14 ± 0.05 | −0.10 (−0.15 to −0.05) | 1.24 ± 0.10 | 1.33 ± 0.16 | 1.33 ± 0.12 | 1.33 ± 0.10 | −0.09 (−0.14 to − 0.03) | ||||
| PCI | 86.0 ± 14.9 | 92.2 ± 16.3 | 92.5 ± 17.0 | 106.9 ± 17.6 | 8.2 (2.2 to 14.1) | 86.0 ± 14.9 | 85.7 ± 18.3 | 92.5 ± 17.0 | 91.0 ± 20.8 | −0.6 (−8.0 to 6.8) | ||||
| APC-sr | 4.60 ± 1.02 | 5.95 ± 1.38 | 4.29 ± 1.00 | 7.06 ± 1.40 | 1.41 (0.76 to 2.07) | 4.60 ± 1.02 | 4.09 ± 0.97 | 4.29 ± 1.00 | 4.10 ± 1.04 | 0.32 (−0.05 to 0.68) | ||||
. | Levonorgestrel-containing OC . | . | Desogestrel-containing OC . | . | Mean difference in change (95% CI) . | Levonorgestrel only . | . | Desogestrel only . | . | Mean difference in change (95% CI)‡ . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | No use, mean ± SD . | OC use, mean ± SD . | No use, mean ± SD . | OC use, mean ± SD . | . | No use,†mean ± SD . | OC use, mean ± SD . | No use, mean ± SD . | OC use, mean ± SD . | . | ||||
| Factor VLeiden-negative | ||||||||||||||
| Protein C | 96.0 ± 18.3 | 108.8 ± 21.7 | 92.0 ± 14.0 | 103.7 ± 17.8 | −1.1 (−7.2 to 5.0) | 96.7 ± 18.3 | 92.7 ± 18.6 | 92.0 ± 14.0 | 84.9 ± 11.5 | −3.1 (−6.8 to 0.6) | ||||
| Protein S total | 88.5 ± 13.2 | 83.4 ± 13.6 | 85.9 ± 9.9 | 71.7 ± 10.2 | − 9.1 (−13.4 to −4.7) | 88.6 ± 13.4 | 94.9 ± 13.4 | 85.9 ± 9.9 | 92.5 ± 13.2 | 0.3 (−4.2 to 4.7) | ||||
| Protein S free | 39.9 ± 7.0 | 43.9 ± 8.0 | 38.9 ± 5.8 | 33.8 ± 7.5 | −9.2 (−12.0 to −6.4) | 40.0 ± 7.1 | 47.9 ± 8.4 | 38.9 ± 5.8 | 42.7 ± 7.1 | −4.0 (−6.4 to −1.7) | ||||
| C4BP | 89.9 ± 20.1 | 77.1 ± 17.3 | 88.8 ± 15.8 | 79.1 ± 15.1 | 2.6 (−1.5 to 6.6) | 89.2 ± 20.3 | 82.0 ± 15.8 | 88.8 ± 15.8 | 87.5 ± 17.8 | 6.0 (0.03 to 12.0) | ||||
| PSAPCind | 1.32 ± 0.12 | 1.19 ± 0.08 | 1.34 ± 0.13 | 1.14 ± 0.07 | −0.08 (−0.13 to −0.02) | 1.32 ± 0.12 | 1.46 ± 0.23 | 1.34 ± 0.13 | 1.35 ± 0.13 | −0.13 (−0.20 to −0.06) | ||||
| PCI | 90.6 ± 16.6 | 101.0 ± 15.0 | 90.5 ± 13.7 | 99.5 ± 18.1 | −1.4 (−8.4 to 5.6) | 88.9 ± 14.6 | 90.4 ± 17.7 | 90.5 ± 13.7 | 90.0 ± 14.4 | −2.0 (−7.8 to 3.9) | ||||
| APC-sr | 1.92 ± 0.61 | 3.26 ± 0.72 | 2.04 ± 0.63 | 3.76 ± 0.77 | 0.38 (0.08 to 0.67) | 1.93 ± 0.63 | 1.58 ± 0.61 | 2.04 ± 0.63 | 1.80 ± 0.52 | 0.11 (−0.09 to 0.30) | ||||
| Factor VLeiden-positive | ||||||||||||||
| Protein C | 92.1 ± 12.3 | 102.5 ± 16.3 | 106.6 ± 15.9 | 122.7 ± 22.2 | 5.7 (−1.8 to 13.3) | 92.1 ± 12.3 | 86.2 ± 11.1 | 106.6 ± 15.9 | 96.5 ± 14.9 | −4.2 (−9.0 to 0.7) | ||||
| Protein S total | 88.2 ± 11.4 | 85.9 ± 12.9 | 96.9 ± 10.9 | 77.6 ± 11.1 | −16.9 (−23.8 to −10.1) | 88.2 ± 11.4 | 95.2 ± 10.5 | 96.9 ± 10.9 | 100.6 ± 11.2 | −3.2 (−8.1 to 1.6) | ||||
| Protein S free | 42.2 ± 9.4 | 45.9 ± 9.9 | 42.1 ± 8.1 | 35.3 ± 8.4 | −10.5 (−15.0 to − 5.9) | 42.2 ± 9.4 | 48.9 ± 7.8 | 42.1 ± 8.1 | 45.9 ± 6.8 | −2.9 (−5.9 to 0.1) | ||||
| C4BP | 80.5 ± 11.2 | 72.3 ± 9.8 | 101.5 ± 12.7 | 85.4 ± 16.6 | −8.0 (−13.9 to −2.1) | 80.5 ± 11.2 | 75.1 ± 9.7 | 101.5 ± 12.7 | 95.3 ± 12.1 | −0.8 (−6.4 to 4.9) | ||||
| PSAPCind | 1.24 ± 0.10 | 1.16 ± 0.10 | 1.33 ± 0.12 | 1.14 ± 0.05 | −0.10 (−0.15 to −0.05) | 1.24 ± 0.10 | 1.33 ± 0.16 | 1.33 ± 0.12 | 1.33 ± 0.10 | −0.09 (−0.14 to − 0.03) | ||||
| PCI | 86.0 ± 14.9 | 92.2 ± 16.3 | 92.5 ± 17.0 | 106.9 ± 17.6 | 8.2 (2.2 to 14.1) | 86.0 ± 14.9 | 85.7 ± 18.3 | 92.5 ± 17.0 | 91.0 ± 20.8 | −0.6 (−8.0 to 6.8) | ||||
| APC-sr | 4.60 ± 1.02 | 5.95 ± 1.38 | 4.29 ± 1.00 | 7.06 ± 1.40 | 1.41 (0.76 to 2.07) | 4.60 ± 1.02 | 4.09 ± 0.97 | 4.29 ± 1.00 | 4.10 ± 1.04 | 0.32 (−0.05 to 0.68) | ||||
The individual plasma components are expressed as percent of normal pooled plasma. PCI indicates protein C inhibitor; APC-sr, activated protein C sensitivity ratio; C4BP, C4b-binding protein; and PSAPCind, APC-independent anticoagulant activity of protein S.
Formula: (no use of levonorgestrel containing OC - use of levonorgestrel containing OC) - (no use of desogestrel containing OC - use of desogestrel containing OC).
For this analysis, one woman was excluded due to protocol violation in phase 2.
Formula: (no use of levonorgestrel - use of levonorgestrel) - (no use of desogestrel - use of desogestrel).