EE has been found to have disproportionate effects on liver protein synthesis and VTE risk regardless of whether the route of administration is oral, transdermal, or vaginal, indicating that the use of parenteral routes over the oral route does not result in EE having proportional hepatic actions relative to non-hepatic actions. However, the potency of EE on liver protein synthesis is in any case reduced with parenteral administration. A dosage of 10 µg/day vaginal EE has been found to be equivalent to 50 µg oral EE in terms of effects on liver protein synthesis, such as stimulation of hepatic SHBG production. As such, parenteral EE, which bypasses the first pass through the liver that occurs with oral EE, has been found to have a 5-fold lower impact on liver protein synthesis by weight than oral EE. In contrast to EE as well as to oral estradiol, transdermal estradiol shows few or no effects on liver protein synthesis at typical menopausal dosages.