Background: At the request of researchers in the UK, we conducted a case-control study to explore the relation between use of postmenopausal oestrogen hormone replacement therapy (HRT) and idiopathic venous thromboembolism (VTE).
Methods: The study was based on information derived from Group Health Cooperative of Puget Sound for the period 1980 to 1994. Women aged 50-74 years admitted to hospital for idiopathic VTE were identified from hospital records. The diagnosis of idiopathic VTE was validated from the clinical record. Women who had medical conditions predisposing to VTE (a history of VTE or cancer, recent trauma, or surgery) were excluded as cases. Four control subjects matched to each case by age, duration of Cooperative membership, and calendar time were identified from the base population. Various potential risk factors were recorded based on record review.
Findings: An initial analysis of 42 cases and 168 matched controls yielded a matched relative risk estimate of 3.6 (95% CI 1.6-7.8) for current users of oestrogens compared with non-users. There was a substantial effect of daily oestrogen dose. The matched relative risk estimates for oestrogen users of 0.325 mg, 0.625 mg, and 1.25 mg or more daily were 2.1, 3.3, and 6.9, respectively. Body-mass index was independently associated with the risk of VTE but did not materially confound the relation of oestrogen and VTE. The absolute risk of idiopathic VTE is estimated to be low (0.9 x 10(-4) woman-years) in non-users of oestrogen; the risk in current users is estimated at 3.2 x 10(-4) woman-years.
Interpretation: The risk of idiopathic VTE is about three times higher among current users of replacement oestrogens than among non-users. However, the absolute risk is low for both groups and accounts for only a modest increase in morbidity.