ArticlesRisk of venous thromboembolism in users of hormone replacement therapy
Introduction
Most studies linking the use of oestrogen to increased risk of venous thromboembolism (VTE) have been carried out in young women in relation to use of oral contraceptives.1 Hormone replacement therapy (HRT) is not generally believed to carry a similar risk in postmenopausal women. Although none of the studies to address this issue has found a significant increase in VTE associated with HRT,2, 3, 4, 5 each lacked power to detect important risks. The British National Formulary6 states that the evidence of an increased thrombotic risk associated with HRT is questionable, but lists active thrombophlebitis or thromboembolic disorders as contraindications to treatment. Similarly, although a working party of the UK Royal College of Obstetricians and Gynaecologists on prophylaxis against thromboembolism concluded that there was insufficient evidence to suggest that HRT is associated with an increased risk of VTE, their report acknowledged the need for further research.7
Our study was undertaken to investigate a possible association between current use of HRT and the risk of idiopathic deep-vein thrombosis (DVT) and pulmonary embolism (PE). The protocol was based on that of a case-control study to examine the association between oral-contraceptive use and VTE in young women.8
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Cases
Cases were recruited between February, 1993, and December, 1994, from hospitals in the area of the Oxford Regional Health Authority (as defined before April, 1994) by twice-weekly screening of all relevant wards. Eligible cases were women aged 45–64 years with a suspected diagnosis of PE, DVT, or both. Women with a history of PE, DVT, stroke, or myocardial infarction, and those with a history within the previous 6 weeks of surgery, pregnancy, trauma, or illness necessitating bed rest for longer
Results
108 cases (69 with DVT and 39 with PE) and 232 controls satisfied all inclusion criteria. The proportions of cases with definite, probable, possible, and other diagnostic certainty ratings were 73%, 20%, 4%, and 3% for DVT, and 33%, 51%, 10%, and 5% for PE. Cases in the 'other' category were excluded from all further analyses. Participants without matching cases or controls were also excluded. 103 cases and 178 controls remained; of these, 22 cases and 32 controls had been recruited
Discussion
The results of our study and those of Jick and colleagues12 suggest a possible causal relation between current HRT use and idiopathic VTE. This interpretation is supported by results from a study of exogenous hormones in relation to risk of PE by Grodstein and colleagues.13 In our study, risk of VTE seemed to be highest among short-term users, whereas no association was seen with past use. Although the magnitude of estimated risk was greater among users of higher-dose preparations than among
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