The effect of hormone replacement therapy of the age-related rise of factor VIIc, and its activity state

Although hormone replacement therapy (HRT) appears to protect women from ischaemic heart disease (IHD), its use is associated with increased factor clotting activity (VIIc), an independent risk factor for IHD. The nature of this factor VII rise was therefore examined in a cross-sectional study of 279 women aged between 40 and 65 years. Ninety-four were pre-menopausal, 44 were post-menopausal and taking HRT, whilst 141 were post-menopausal non-users. For those women on oestrogen-only HRT, the mean factor VIIc was 144%, compared to 130% for post-menopausal non-users, and 116% for those on combined HRT. These differences were significant (p = 0.01). Oestrogen-only users also had significantly higher mean levels of factor VIIa (3.3 ng/ml) compared to non-users (2.2 ng/ml) and those on oestrogen-progestogen HRT (2.2 ng/ml-p = 0.015). In contrast for factor VII antigen the mean values of the three groups were similar. Analysis of the age-regression slopes showed a significant age-related rise in factor VIIc of 1.2% per annum (p < 0.01) for post-menopausal non-users. There was a similar increase in factor VII antigen (2.1%) but no rise in factor VIIa. For all HRT users there was no change with age for any of the factor VII measures. Thus the age-related rise in factor VIIc appears to be due to an increase in factor VII zymogen alone, and taking HRT seems to abolish such a rise. In contrast, the increased factor VIIc seen with oestrogen-only HRT appears to be secondary to factor VII activation.