The Safety of Oral Versus Transdermal Estrogen

Denise Black, MD, FRCSC


Menopause. 2020;27(11):1328-1329. 

In This Article

Abstract and Introduction


There exists a growing number of treatment options available to women who choose hormone therapy for management of systemic menopause symptoms. Choosing the product that is the "best fit" for each individual woman can be a challenging task. One of these decisions pertains to the optimal route of estrogen administration. This Practice Pearl will explore some of the differences between oral and transdermal estrogens.


The two most common routes of systemic estrogen administration are oral and transdermal. Assuming that equivalent dosing is used, they are both efficacious for relief of menopause symptoms and preservation of bone health. However, there are important differences with respect to the metabolism of estrogens. Oral estrogens are metabolized in the first pass by the liver, producing different metabolic effects not seen with transdermal administration. Some of the positive effects of first-pass hepatic metabolism include larger reductions in low-density lipoprotein cholesterol levels, lipoprotein(a), and larger increases in high-density lipoprotein cholesterol compared with transdermal administration. The negative effects of first-pass metabolism include increase in triglycerides and a dose-dependent increase in coagulation factors (factor VII antigen, activated factor VII, and prothrombin fragment 1 and 2), leading to a potentially increased risk for venous thromboembolism (VTE).[1]