How to lower estrone levels in a patient using exogenous estrogen (external estrogen)?

From the Guidelines

To lower estrone levels in a patient using exogenous estrogen, switching to transdermal estradiol is recommended as it bypasses the first-pass liver metabolism, reducing the conversion of estradiol to estrone. This approach is supported by the fact that transdermal administration of 17β-estradiol mimics physiological serum estradiol concentrations, providing a better safety profile than oral formulations 1. The transdermal route avoids the hepatic first pass effect and minimizes the impact of estrogens on the synthesis of hemostatic factors, which can contribute to the formation of estrone.

Key considerations for implementing this recommendation include:

• Using transdermal estradiol patches, gels, or creams, which typically deliver 0.025-0.1 mg/day through patches changed twice weekly, or 0.5-1.0 mg/day via gels or creams applied daily.
• Selecting bioidentical estradiol over synthetic estrogens or conjugated equine estrogens, as these may have different metabolic profiles that could influence estrone levels.
• If oral administration must be continued, using the lowest effective dose of estradiol, typically 0.5-1 mg daily, to minimize estrone conversion.
• Regularly monitoring hormone levels to ensure the intervention's effectiveness and to adjust dosing as necessary.

Additionally, addressing factors that increase aromatization of androgens to estrogens, such as reducing excess body fat or managing insulin resistance, can also contribute to lowering estrone levels independently of the exogenous estrogen therapy approach. The choice of transdermal estradiol is further supported by its beneficial effects on circulating lipids, markers of inflammation, and blood pressure, as well as its effectiveness in achieving a bone mineral density peak and reducing bone resorption markers 1.

From the FDA Drug Label

The growth of many cancers of the breast is stimulated or maintained by estrogens. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol Anastrozole is a selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations

To lower estrone levels in a patient using exogenous estrogen, anastrozole may be considered as it is a selective non-steroidal aromatase inhibitor that significantly lowers serum estradiol concentrations. However, the effect of anastrozole on estrone levels is not directly stated in the label.

• The label does mention that anastrozole lowers estradiol levels by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing.
• It is essential to note that anastrozole's primary mechanism is to inhibit the aromatase enzyme, which converts androgens to estrogens, including estrone and estradiol. Since the patient is using exogenous estrogen, the effectiveness of anastrozole in lowering estrone levels may be limited, as anastrozole primarily targets the conversion of androgens to estrogens, not the exogenous estrogen itself 2.

From the Research

Lowering Estrone Levels in Patients Using Exogenous Estrogen

To lower estrone levels in a patient using exogenous estrogen, several strategies can be considered:

• Reducing the dose of exogenous estrogen: Using lower doses of estrogen can help decrease estrone levels, as higher doses can lead to increased estrone production 3.
• Switching to a different estrogen product: Different estrogen products can have varying effects on estrone levels. For example, transdermal products may produce lower estrone levels compared to oral products due to bypassing the first-pass effect 4.
• Using aromatase inhibitors: Aromatase inhibitors, such as letrozole and anastrozole, can suppress the production of estrogens, including estrone, by inhibiting the aromatase enzyme 5, 6.
• Considering the patient's body mass index (BMI): The effectiveness of aromatase inhibitors in suppressing estrone levels may be related to BMI, with higher BMIs potentially requiring more potent inhibitors or higher doses 6.

Estrogen Products and Estrone Levels

Different estrogen products can affect estrone levels in various ways:

• Oral estrogens: Oral estrogens have minimal systemic bioavailability due to gut and liver metabolism, but can still produce high concentrations of estrone 4.
• Transdermal products: Transdermal products, such as patches or gels, can produce higher concentrations of estradiol and lower concentrations of estrone compared to oral products 4.
• Vaginal products: Vaginal products, such as rings or creams, can achieve high serum concentrations of estrogens, including estrone 4.

Aromatase Inhibitors and Estrone Suppression

Aromatase inhibitors can effectively suppress estrone levels:

• Letrozole: Letrozole has been shown to be a more potent suppressor of total-body aromatization and plasma estrogen levels, including estrone, compared to anastrozole 5.
• Anastrozole: Anastrozole can also suppress estrone levels, but may be less effective in patients with higher BMIs 6.