Boston—Postmenopausal women on hormone replacement therapy (HRT) are known to be at increased risk of venous thromboembolism (VTE). But whether the route of administration influences the risk was not known until now.
Investigators at Kings College Hospital NHS Foundation Trust in London discovered that VTE risk is increased in women using oral HRT but not in those using a transdermal patch. Catherine N. Bagot, MD, reported these results at the 22nd Congress of the International Society on Thrombosis and Haemostasis (ISTH).
The investigators have thus far recruited 155 women to this ongoing study, 98 on HRT and 57 controls not on HRT. Fifty-four women were on oral HRT and 44 were using the transdermal patch.
Dr Bagot and colleagues used thrombin generation as a marker of thrombotic risk. They found that women taking HRT had significantly higher peak thrombin generation than controls (P=0.0019). They performed a subgroup analysis and the difference was only detectable in women using oral HRT (P<0.0001) and not in women using the transdermal route (P=0.7).
Investigators verified the data further and confirmed that peak thrombin generation was significantly higher in women on oral compared to transdermal HRT (P<0.0001).
The presence of progestogen or testosterone did not have any impact on the results.
These findings indicate that postmenopausal women taking oral HRT are at greater risk for VTE than those using transdermal administration. Dr Bagot suggested that transdermal administration may be safe in women who have had previous VTEs.
The research team also investigated the relationship between estradiol and peak thrombin generation.
They analyzed blood samples of 132 women. Eighty-six women were on HRT, 42 oral and 44 transdermal. The remaining women not on HRT served as controls.
Investigators excluded women whose HRT formulation contained equine estrogens or who had less than 100 pMol/L estradiol levels.
They found that estradiol levels were significantly higher in women using either formulation of HRT than controls. However, the levels were not significantly different between the two HRT groups.
Investigators also found peak thrombin generation to be significantly higher in women on HRT than controls, and this correlated with estradiol concentrations. Women taking oral HRT had a significantly higher peak thrombin generation compared to women using the patch. Investigators observed a correlation between estradiol levels and peak thrombin generation only in women using oral HRT.
Dr Bagot indicated that a limitation of this second study was that there was no way of knowing whether the estradiol levels were at the peak or trough. Nevertheless, this study confirmed further a causal link between oral estrogens, hypercoagulability, and an increased risk of VTE.
The investigators again recommended the transdermal route over oral HRT administration in postmenopausal women to achieve the lowest thrombotic risk.
