Does oral estradiol (Estrogen) reduce Low-Density Lipoprotein (LDL) cholesterol?

From the Guidelines

Oral estradiol does reduce LDL cholesterol levels, with a typical reduction of approximately 10-15% when taken at standard doses (1-2 mg daily) 1.

Key Points

• Oral estradiol undergoes first-pass metabolism through the liver, directly affecting hepatic lipid metabolism by increasing LDL receptor activity, which enhances LDL clearance from the bloodstream.
• The lipid-modifying effects of oral estradiol typically begin within weeks of starting therapy and stabilize after 2-3 months of consistent use.
• Additionally, oral estradiol tends to increase HDL (good cholesterol) by about 5-10% and decrease total cholesterol, but may also increase triglycerides in some individuals.
• While this cholesterol-lowering effect can be beneficial, it's essential to note that oral estradiol should not be prescribed solely for lipid management, as there are more effective medications specifically designed for that purpose.

Considerations

• The most recent and highest quality study on this topic is from 2001, which may not reflect current clinical practices or guidelines 1.
• However, more recent studies on lipid management and cardiovascular disease prevention do not specifically address the effects of oral estradiol on LDL cholesterol levels 1.
• As such, the recommendation to use oral estradiol for lipid management should be made with caution and in consideration of individual patient needs and risk factors.

Clinical Implications

• Oral estradiol may be considered as an adjunctive therapy for lipid management in certain patients, particularly those with menopausal symptoms or other indications for hormone replacement therapy.
• However, the primary approach to lipid management should still involve lifestyle modifications and evidence-based pharmacotherapies, such as statins, as recommended by current guidelines 1.

From the Research

Effects of Oral Estradiol on LDL Cholesterol

• Oral estradiol has been shown to decrease low-density lipoprotein (LDL) cholesterol levels in postmenopausal women 2, 3, 4, 5.
• A study published in the New England Journal of Medicine found that oral conjugated estrogens at doses of 0.625 mg per day and 1.25 mg per day decreased the mean LDL cholesterol level by 15 percent and 19 percent, respectively 3.
• Another study published in Thrombosis and Haemostasis found that oral estradiol (2 mg) significantly lowered plasma LDL cholesterol concentrations, while transdermal estradiol (50 microg) had no effect 4.
• A study published in the Journal of Clinical Endocrinology and Metabolism found that oral 17 beta-estradiol (2 mg/day) accelerated the fractional catabolic rates of all LDL particles studied, resulting in reduced light LDL cholesterol and apoB concentrations 5.

Comparison with Transdermal Estradiol

• Transdermal estradiol has been shown to have a minor decrease in LDL cholesterol levels compared to oral estradiol 2, 6.
• A study published in Maturitas found that transdermal estradiol (50 micrograms/day) and oral conjugated estrogens (0.625 mg/day) both decreased total and LDL cholesterol levels, but the effects on HDL cholesterol and triglycerides differed between the two groups 6.

Mechanism of Action

• The decrease in LDL levels has been shown to result from accelerated LDL catabolism, rather than decreased production 3, 5.
• Oral estradiol has also been shown to increase the production of large, triglyceride-rich VLDL, which is cleared directly from the circulation and not converted to small VLDL or LDL 3.