Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): A randomized, placebo-controlled, 12-week study in early postmenopausal women

Abstract

Objective. To investigate the effects of short-term postmenopausal oral hormone administration on plasma levels of procarboxypeptidase U (proCPU, thrombin-activatable fibrinolysis inhibitor, EC 3.4.17.20), an inhibitor of fibrinolysis, in healthy early postmenopausal women. Design. A prospective, randomized, placebo-controlled study. Setting. Outpatient clinic of the Department of Obstetrics and Gynaecology. Subjects. Seventy-seven healthy early postmenopausal women were screened of whom 65 were randomized. Analyses were based on 60 participants. Interventions. The women received oral micronized oestradiol 2 mg either alone (E2 group, n = 16), or sequentially combined with dydrogesterone 10 mg (E2 + D group, n = 14) or trimegestone 0.5 mg (E2 + T, n = 14), or placebo (n = 16) for 12 weeks. Main outcome measure. ProCPU concentrations at baseline, and at 4 and 12 weeks of treatment. Results. Four weeks of E2 + T was associated with a significant decrease in the fasting proCPU concentration, which was sustained after 12 weeks [t 0: 636 ± 57 U L-1 (mean ± SD); t = 4: 583 ± 63 U L-1; t = 12: 589 ± 48 U L-1; ancova versus placebo: P = 0.011]. The percentage change from baseline versus placebo in this group was -8.4% [95% confidence interval (CI) -15.7 to -1.1] after 4 weeks and -5.9% (95% CI -11.7 to -0.1) after 12 weeks. There were no significant changes versus placebo in the E2 group nor in the E2 + D group. Conclusion. Short-term treatment with E2 + T, but not E2 alone or E2 + D, lowers proCPU concentration. These findings add to accumulating evidence suggesting that different progestagens added to oestrogen replacement may differentially affect the risk of arterial and venous disease.