For non-oral HT , decreases in lipoprotein(a ) , cell adhesion molecules , and factor VII generally were significant , resistance to activated protein C ( APCr ) was slightly increased , and other markers including CRP and homocysteine did not change .
Compared with oral HT , changes in CRP and APCr were smaller , changes in cell adhesion molecules and some fibrinolytic parameters tended to be smaller , whereas changes in other factors including lipoprotein(a ) and homocysteine did not differ .
( S ) Potentially unfavorable changes seen with oral HT on two important markers , CRP and APCr , are substantially smaller with non-oral HT .
Non-oral HT has minor effects on the other cardiovascular risk markers studied .
Therefore , compared with oral HT , non-oral HT appears be safer with respect to atherosclerotic and venous thromboembolic disease risk
OBJECTIVE To review the effects of non-oral administration of postmenopausal hormone therapy ( HT ) on risk markers for atherosclerotic and venous thromboembolic disease .
Non-oral postmenopausal HT appears not to increase venous thromboembolic risk , whereas the effect on coronary heart disease risk is less clear .
Prothrombotic Mutations, Hormone Therapy, and Venous Thromboembolism Among Postmenopausal Women: Impact of the Route of Estrogen Administration
Background — Oral estrogen increases the risk of venous thromboembolism ( VTE ) in postmenopausal women , particularly in those with a prothrombotic mutation .  Transdermal estrogen may be safe with respect to VTE . We investigated the impact of the route of estrogen administration on the association between a prothrombotic mutation ( factor V Leiden or prothrombin G20210A mutation ) and VTE risk . Methods and Results — We performed a multicenter case-control study of VTE among postmenopausal women who were enrolled in 1999 through 2004 at 7 clinical centers in France . We recruited 235 consecutive patients with a first documented episode of idiopathic VTE and 554 controls . Factor V Leiden was associated with a 3.4-fold – increased risk of VTE ( 95 % confidence interval [ CI ] , 2.0 to 5.8 ) , and a prothrombin mutation was associated with a 4.8-fold – increased risk of VTE ( 95 % CI , 2.5 to 9.4 ) . Oral but not transdermal estrogen was associated with an increased risk of VTE ( odds ratio [ OR ] , 4.3 ; 95 % CI , 2.6 to 7.2 ; and OR , 1.2 ; 95 % CI , 0.8 to 1.7 , respectively ) . After adjustment for potential confounding factors , the combination of either factor V Leiden or prothrombin G20210A mutation and oral estrogen gave a 25-fold – increased risk of VTE compared with nonusers without mutation ( 95 % CI , 6.9 to 95.0 ) . However , the risk for women with prothrombotic mutation  using transdermal estrogen was similar to that of women with a mutation who were not using estrogen ( OR , 4.4 ; 95 % CI , 2.0 to 9.9 ; and OR , 4.1 ; 95 % CI , 2.3 to 7.4 , respectively ) . Conclusions — In contrast to oral estrogen , transdermal estrogen does not confer additional risk on women who carry a prothrombotic mutation . The safety of transdermal estrogen has to be confirmed in r and omized trials
For non-oral HT , decreases in lipoprotein(a ) , cell adhesion molecules , and factor VII generally were significant , resistance to activated protein C ( APCr ) was slightly increased , and other markers including CRP and homocysteine did not change .
Compared with oral HT , changes in CRP and APCr were smaller , changes in cell adhesion molecules and some fibrinolytic parameters tended to be smaller , whereas changes in other factors including lipoprotein(a ) and homocysteine did not differ .
( S ) Potentially unfavorable changes seen with oral HT on two important markers , CRP and APCr , are substantially smaller with non-oral HT .
Non-oral HT has minor effects on the other cardiovascular risk markers studied .
Therefore , compared with oral HT , non-oral HT appears be safer with respect to atherosclerotic and venous thromboembolic disease risk
OBJECTIVE To review the effects of non-oral administration of postmenopausal hormone therapy ( HT ) on risk markers for atherosclerotic and venous thromboembolic disease .
Non-oral postmenopausal HT appears not to increase venous thromboembolic risk , whereas the effect on coronary heart disease risk is less clear .