Keramaris N C, Christodoulakos G E, Lambrinoudaki I V, Dalamanga A, Alexandrou A P, Bramis J, Bastounis E, Creatsas G C
Vascular Clinic, 1st Department of Surgery, University of Athens Medical School, Laikon Hospital, Athens, Greece.
Climacteric. 2007 Oct;10(5):400-7. doi: 10.1080/13697130701624773.
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 17beta-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation.
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 17beta-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.
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).
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.
激素疗法可能通过对凝血抑制剂产生负面影响而增加静脉血栓栓塞的风险。本研究旨在评估结合马雌激素单独使用或与醋酸甲羟孕酮联合使用、低剂量17β-雌二醇与醋酸炔诺酮联合使用以及替勃龙对凝血抑制剂的影响。
216名绝经后女性口服以下药物，为期12个月：结合马雌激素0.625毫克（CEE，n = 24）、替勃龙2.5毫克（n = 24）、CEE + 醋酸甲羟孕酮5毫克（CEE/MPA，n = 34）、17β-雌二醇1毫克 + 醋酸炔诺酮0.5毫克（E2/NETA，n = 66）或不接受治疗（对照组，n = 68）。在基线和12个月时测量血浆抗凝血酶、蛋白C和总蛋白S。
CEE、CEE/MPA和E2/NETA治疗与抗凝血酶水平显著降低相关（CEE：基线235.6±47.6毫克/升，随访221.3±48.3毫克/升，p = 0.0001；CEE/MPA：基线251.1±38.6毫克/升，随访225.0±42.6毫克/升，p = 0.009；E2/NETA：基线257.1±59.4毫克/升，随访227.1±50.4毫克/升，p = 0.007；替勃龙：基线252.6±62.4毫克/升，随访261.9±59.1毫克/升，p = 0.39）。CEE和CEE/MPA组中蛋白C显著降低（CEE：基线3.64±1.17毫克/升，随访2.48±1.47毫克/升，p = 0.004；CEE/MPA：基线3.24±1.23毫克/升，随访2.61±1.38毫克/升，p = 0.001；E2/NETA：基线3.24±1.10毫克/升，随访3.15±1.11毫克/升，p = 0.08；替勃龙：基线3.26±1.25毫克/升，随访3.09±1.32毫克/升，p = 0.37）。仅CEE/MPA组中蛋白S显著降低（CEE：基线19.4±2.76毫克/升，随访18.0±2.45毫克/升，p = 0.56；CEE/MPA：基线18.4±3.42毫克/升，随访14.5±3.43毫克/升，p = 0.005；E2/NETA：基线19.0±3.11毫克/升，随访19.5±3.43毫克/升，p = 0.18；替勃龙：基线18.5±3.09毫克/升，随访18.0±4.09毫克/升，p = 0.32）。
雌激素和雌激素 - 孕激素疗法与凝血抑制剂减少有关，减少程度取决于所采用的治疗方案。替勃龙似乎对凝血抑制剂没有影响。
