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


METHODS
A prospective, randomized, placebo-controlled study.


METHODS
Outpatient clinic of the Department of Obstetrics and Gynaecology.


METHODS
Seventy-seven healthy early postmenopausal women were screened of whom 65 were randomized. Analyses were based on 60 participants.


METHODS
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.


METHODS
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 +/- 63UL-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.


CONCLUSIONS
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.
Post
M S
MS
Project 'Ageing Women' and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Amsterdam, The Netherlands.
Hendriks
D F
DF
Van Der Mooren
M J
MJ
Van Baal
W M
WM
Leurs
J R
JR
Emeis
J J
JJ
Kenemans
P
P
Stehouwer
C D A
CD
D025901:Carboxypeptidase B2 / Q000097:blood*; D004958:Estradiol; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology; D011397:Promegestone / Q000031:analogs & derivatives; D011446:Prospective Studies
C050319:trimegestone; D004958:Estradiol; D011397:Promegestone; D025901:Carboxypeptidase B2