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

Post MS, Hendriks DF, van der Mooren MJ, van Baal WM, Leurs JR, Emeis JJ, Kenemans P, Stehouwer CDA (VU university medical center, Amsterdam, The Netherlands; University of Antwerp, Wilrijk, Belgium; and Gaubius Laboratory, TNO-PG, Leiden, The Netherlands). Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebo-controlled, 12-week study in early postmenopausal women. J Intern Med 2002; 251: 245–251. 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.