From the Guidelines
Transdermal estradiol has a more beneficial profile on circulating lipids compared to oral estradiol, as it avoids the hepatic first pass effect and minimizes the impact of estrogens on the synthesis of hemostatic factors. The difference in lipid effects between oral and transdermal estradiol is attributed to the route of administration, with oral estradiol undergoing first-pass metabolism in the liver, which stimulates the production of HDL ("good") cholesterol while reducing LDL ("bad") cholesterol and total cholesterol, but also increasing triglyceride levels 1. In contrast, transdermal estradiol bypasses the liver's first-pass metabolism, resulting in more neutral effects on lipids.
- Key differences in lipid effects:
- Oral estradiol: increases HDL, reduces LDL and total cholesterol, but also increases triglycerides
- Transdermal estradiol: minimal changes in HDL, LDL, and total cholesterol levels, and does not increase triglycerides
- Typical dosing for transdermal estradiol: 50-100 micrograms daily, which can be achieved through patches changed once or twice weekly, while oral estradiol is commonly prescribed at 1-2 mg daily 1.
- The preferred route of administration is transdermal, as it mimics the physiological serum estradiol concentrations, providing a better safety profile than oral formulations, including a more beneficial profile on circulating lipids, markers of inflammation, and blood pressure 1.
From the Research
Differences in Lipid Profiles
The differences between oral and transdermal estradiol in terms of effects on lipid profiles are as follows:
- Oral estradiol tends to increase high-density lipoprotein (HDL) cholesterol levels more significantly than transdermal estradiol 2, 3, 4.
- Transdermal estradiol is more effective in reducing serum triglyceride levels compared to oral estradiol 2, 3, 5.
- Both oral and transdermal estradiol can decrease total and low-density lipoprotein (LDL) cholesterol levels, although the extent of these changes may vary between the two routes of administration 2, 6, 3.
- The effects of oral and transdermal estradiol on lipid profiles can have implications for cardiovascular health, with transdermal estradiol potentially being a better option for women with high serum triglyceride levels 3, 5.
Specific Lipid Parameters
The effects of oral and transdermal estradiol on specific lipid parameters are:
- Triglycerides: decreased with transdermal estradiol 2, 3, 5, slightly increased or unchanged with oral estradiol 2, 3, 4.
- HDL cholesterol: increased with oral estradiol 2, 3, 4, decreased or unchanged with transdermal estradiol 2, 3.
- LDL cholesterol: decreased with both oral and transdermal estradiol 2, 6, 3.
- Total cholesterol: decreased with both oral and transdermal estradiol 2, 6, 3.
Clinical Implications
The clinical implications of these differences are:
- Transdermal estradiol may be a better option for women with high serum triglyceride levels or those who require a more favorable effect on triglyceride metabolism 3, 5.
- Oral estradiol may be more effective in increasing HDL cholesterol levels, which could be beneficial for women with low HDL cholesterol levels 2, 3, 4.
- The choice between oral and transdermal estradiol should be based on individual patient characteristics and lipid profiles, as well as other factors such as cardiovascular risk and overall health status 2, 6, 3, 5, 4.