Reproductive history, hormone replacement, and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology


Aaron R. Folsom, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454-1015, USA. E-mail:


Numerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1·6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR = 1·60, 95% confidence interval [CI], 1·06–2·36; Population attributable fraction = 6·7%, 95%CI, 1·0–10·3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR = 2·02, 95%CI, 1·31–3·12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR = 2·40, 95%CI, 1·40–4·12) than those with secondary VTE (RR = 1·08, 95%CI, 0·63–1·85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE.