Summary
Recent data has shown that hormone therapy (HT) increases the risk of cardiovascular
and thromboembolic disease, particularly in users of oral HT. Phytoestrogens are popular
alternatives to oestrogen therapy; however, their effects on cardiovascular risk are
unknown. We investigated the effect of the phytoestrogen, genistein on the expression
of genes and proteins from the haemostatic system in the liver in an ovariectomised
rat model. Fifty-nine virgin female Sprague-Dawley rats were fed with soy-free chow
supplemented with 17β estradiol (E2) (daily uptake 0.19 or 0.75 mg/kg body weight),
or genistein (daily up-take 6 or 60 mg/kg body weight), for three months and compared
to soy-free control rats. Gene expression of prothrombin, factor VII, fibrinogen alpha
and fibrinogen beta was increased with E2 and genistein compared to the soy-free control
group (p<0.001). Genistein increased factor VII significantly more than E2 (p<0.005).
Plasminogen mRNA was increased in both treatment groups compared to the soy-free control,
with genistein expression significantly higher than E2 (p<0.001). Tissue plasminogen
inhibitor (tPA), plasminogen activator inhibitor-1 (PAI-1) and C-reactive protein
(CRP) expression were also increased in both groups relative the soy-free control.
Results of protein analysis largely concurred with those of the mRNA. Oestrogen receptor
β (ERβ) was undetected while oestrogen receptor α (ERα) was detected in each sample
group. Genistein can increase the expression of coagulation and fibrinolytic genes.
This effect was similar and in some cases higher than 17β estradiol. These results
suggest that genistein may not be neutral with respect to the haemostatic system.
Keywords
Haemostasis - phytoestrogen - menopause - thrombosis
