Low fibrinogen level: A predisposing factor for venous thromboembolic events with hormone replacement therapy

Several studies have reported an association between hormone replacement therapy (HRT) in postmenopausal women and increased risk of idiopathic venous thromboembolic events (VTEs). Given the widespread use of HRT, it is important to identify factors that may predispose women on HRT to VTEs. To address this concern, we examined potential risk factors for VTEs in women assigned to HRT in the Postmenopausal Estrogen/Progestin Interventions (PEPI) study, a three-year, double-blinded, placebo-controlled trial of 875 postmenopausal women designed to assess the effects of HRT on heart disease risk factors (HDL cholesterol, fibrinogen, blood pressure, and insulin). Women with a history of estrogen-associated VTEs were excluded from the trial. Ten women, all assigned to HRT, had a VTE during PEPI. Only baseline fibrinogen varied significantly between those who did (mean = 249.0 mg/dl) and did not (mean = 280.8 mg/dl) have a VTE while assigned to HRT (P < 0.03). Adjusting for covariates including age, smoking, body mass index, lipid levels, blood pressure, alcohol, exercise, and prior HRT or oral contraceptive use did not affect this finding. The significantly lower fibrinogen levels seen among women subsequently reporting VTEs may be a marker for a specific, but as yet undefined, coagulopathy that is magnified in the presence of exogenous hormones. However, larger studies are needed to confirm this finding.