Risk of venous thromboembolism in users of hormone replacement therapy

Abstract

The association between current use of oral contraceptives and increased risk of venous thromboembolism (VTE) has been firmly established. Although data-sheets for hormone replacement therapy (HRT) carry similar warnings as regards VTE, evidence of an association is inconclusive. We carried out a hospital-based case-control study to investigate whether current use of HRT is associated with VTE. We screened all women aged 45-64 years admitted to hospitals in the area of the Oxford Regional Health Authority with a suspected diagnosis of VTE between February, 1993, and December, 1994. We recruited 81 cases of idiopathic VTE and 146 hospital controls with disorders of eyes, skin, ears, respiratory and alimentary tracts, kidneys, bones, and joints, and trauma; controls were matched to cases for age-group and date and district of admission. To increase the study power, an additional 22 cases of idiopathic VTE and 32 hospital controls admitted before February, 1993, were recruited retrospectively. Participants were questioned about medical and gynaecological history, use of oral contraceptives and HRT, use of other drugs within the previous 3 months, and lifestyle and socioeconomic characteristics. Detailed diagnostic data were extracted from the notes of eligible cases. Matched analyses, adjusted for body-mass Index, socioeconomic group, and history of varicose veins, were undertaken by conditional logistic regression. 44 (42.7%) cases and 44 (24.7%) controls were current users of HRT. The adjusted odds ratio for VTE in current users of HRT compared with non-users (never-users and past users combined) was 3.5 (95% CI 1.8-7.0; p < 0.001). No association was found with past use, and risk appeared to be highest among short-term current users (adjusted likelihood ratio test of trend in odds ratios across different durations of current use, p = 0.011). Current HRT use is associated with risk of VTE. The increased risk may be concentrated in new users. The number of extra cases appears to be only about one in 5000 users per year. These findings need to be weighed against the probable benefits of long-term treatment, including reductions in risks of osteoporotic fracture and coronary heart disease, and the probable modest increase in risk of breast cancer.