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Thromb Haemost 2000; 84(06): 961-967
DOI: 10.1055/s-0037-1614156
Review Article
Schattauer GmbH

Increased Risk of Recurrent Venous Thromboembolism during Hormone Replacement Therapy

Results of the Randomized, Double-blind, Placebo-controlled Estrogen in Venous Thromboembolism Trial (EVTET)
Else Høibraaten
,
Erik Qvigstad
1   Department of Gynecology, Oslo, Norway
,
Harald Arnesen
2   Department of Cardiology, Ullevål University Hospital, Oslo, Norway
,
Stig Larsen
3   Parexel Medstat, Lillestrøm, Norway, and 4Novo Nordisk Pharma AS, Oslo, Norway
,
Egil Wickstrøm
4   From the Department of Hematology, Hematological Research Laboratory, Oslo, Norway
,
Per Morten Sandset
› Author AffiliationsWe are indepted to all the women who contributed enthusiastically to the trial and to Trine Opstad Andersen, Marie-Christine Mowinckel, Ingebjørg Seljeflot, and Gro Gjønnes for excellent laboratory support. Barry Andrews, Per Asbridge, and Ståle Gautvik were responsible for monitoring the study. Heidi Walsøe was responsible for the statistical report. We are also grateful to Ole-Erik Iversen and Katariina Laine, and to Mette Moen who contributed to randomisation of women in Bergen and Trondheim. This work was supported by grants from Novo-Nordisk Pharma, Norway, and Research Forum, Ullevål University Hospital, Oslo, Norway.
Further Information

Publication History

Received 23 March 2000

Accepted after revision 30 June 2000

Publication Date:
13 December 2017 (online)

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Summary

Recent observational studies suggest a 2-4 fold increased risk of venous thromboembolism (VTE) in women taking hormone replacement therapy (HRT). The present study was started before publication of these studies, and the aim was to determine if HRT alters the risk of VTE in high risk women. The study was a randomized, double-blind, and placebo-controlled clinical trial with a doubletriangular sequential design. Females with previously verified VTE were randomized to 2 mg estradiol plus 1 mg norethisterone acetate, 1 tablet daily (n = 71) or placebo (n = 69). The primary outcome was recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE). Between 1996 and 1998 a total of 140 women were included. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. Eight women in the HRT group and one woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. The sequential design did not stop the study, but strongly indicated a difference between the two groups. Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. The results also support those of recent epidemiological studies, which also indicate increased risk of VTE in non-selected female populations during HRT.

Key words

Clinical trial - venous thromboembolism - hormone replacement therapy - estrogen
 

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