The differential effect of estrogen, estrogen–progestin and tibolone on coagulation inhibitors in postmenopausal women

Abstract

Objectives Hormone therapy increases the risk of venous thromboembolism, possibly through a negative effect on coagulation inhibitors. The aim of the study was to assess the effect of conjugated equine estrogens alone or in combination with medroxyprogesterone acetate, low-dose 17β-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation.

Methods Two hundred and sixteen postmenopausal women received orally either conjugated equine estrogens 0.625 mg (CEE, n = 24) or tibolone 2.5 mg (n = 24) or CEE + medroxyprogesterone acetate 5 mg (CEE/MPA, n = 34) or 17β-estradiol 1 mg + norethisterone acetate 0.5 mg (E2/NETA, n = 66) or no therapy (control, n = 68) for 12 months. Plasma antithrombin, protein C and total protein S were measured at baseline and at 12 months.

Results CEE, CEE/MPA and E2/NETA treatment were associated with a significant decrease in antithrombin levels (CEE: baseline 235.6 ± 47.6 mg/l, follow-up 221.3 ± 48.3 mg/l, p = 0.0001; CEE/MPA: baseline 251.1 ± 38.6 mg/l, follow-up 225.0 ± 42.6 mg/l, p = 0.009; E2/NETA: baseline 257.1 ± 59.4 mg/l, follow-up 227.1 ± 50.4 mg/l, p = 0.007; tibolone: baseline 252.6 ± 62.4 mg/l, follow-up 261.9 ± 59.1 mg/l, p = 0.39). Protein C decreased significantly in the CEE and CEE/MPA groups (CEE: baseline 3.64 ± 1.17 mg/l, follow-up 2.48 ± 1.47 mg/l, p = 0.004; CEE/MPA: baseline 3.24 ± 1.23 mg/l, follow-up 2.61 ± 1.38 mg/l, p = 0.001; E2/NETA: baseline 3.24 ± 1.10 mg/l, follow-up, 3.15 ± 1.11 mg/l, p = 0.08; tibolone: baseline 3.26 ± 1.25 mg/l, follow-up 3.09 ± 1.32 mg/l, p = 0.37). Protein S decreased significantly only in the CEE/MPA group (CEE: baseline 19.4 ± 2.76 mg/l, follow-up 18.0 ± 2.45 mg/l, p = 0.56; CEE/MPA: baseline 18.4 ± 3.42 mg/l, follow-up 14.5 ± 3.43 mg/l, p = 0.005; E2/NETA: baseline 19.0 ± 3.11 mg/l, follow-up 19.5 ± 3.43 mg/l, p = 0.18; tibolone: baseline 18.5 ± 3.09 mg/l, follow-up 18.0 ± 4.09 mg/l, p = 0.32).

Conclusions Estrogen and estrogen–progestin therapy are associated with a reduction in coagulation inhibitors, the extent of which depends on the regimen administered. Tibolone appears to have no effect on inhibitors of coagulation.

Key words:

• Hormone therapy
• Antithrombin
• Protein C
• Protein S
• Tibolone
• Estradiol
• Conjugated equine estrogens