What are the implications of elevated estradiol (estrogen) levels in a male patient undergoing testosterone (hormone replacement therapy) with normal testosterone levels?

From the Guidelines

If a male on testosterone therapy has elevated estradiol levels despite good testosterone levels, consult with your healthcare provider about adding an aromatase inhibitor such as anastrozole or exemestane to address the conversion of testosterone to estradiol. This approach is based on the understanding that high estradiol levels in males can lead to symptoms like gynecomastia, water retention, mood changes, and decreased libido, as noted in various clinical contexts 1.

Key Considerations

• The use of aromatase inhibitors like anastrozole (typically 0.5-1mg once or twice weekly) or exemestane (12.5-25mg weekly) can help in managing elevated estradiol levels by inhibiting the enzyme aromatase, which is responsible for the conversion of testosterone to estradiol.
• It is crucial for the healthcare provider to monitor both testosterone and estradiol levels regularly after starting an aromatase inhibitor to ensure a proper balance is maintained, as excessively low estradiol can negatively affect bone density and cardiovascular health.
• Lifestyle modifications, such as maintaining a healthy body weight and reducing alcohol consumption, may also be beneficial, as excess body fat is known to increase aromatase activity.

Important Points to Discuss with Your Healthcare Provider

• The potential benefits and risks of adding an aromatase inhibitor to your current testosterone therapy regimen.
• The importance of regular monitoring of hormone levels to avoid excessively low estradiol levels, which can have negative health consequences.
• How lifestyle changes can complement medical treatment in managing estradiol levels and overall health. Given the potential for significant morbidity associated with unmanaged high estradiol levels in men, including impacts on quality of life, it is essential to work closely with a healthcare provider to find the right balance of hormone levels 1.

From the FDA Drug Label

ADVERSE REACTIONS The following adverse reactions in the male have occurred with some androgens: Endocrine and urogenital: Gynecomastia and excessive frequency and duration of penile erections. The FDA drug label does not answer the question.

From the Research

Elevated Estradiol Levels in Men on Testosterone Therapy

If a male's estradiol level is elevated while on testosterone therapy, but their testosterone level is good, several options can be considered:

• Monitoring of estradiol levels: According to a survey of ISSM members 2, approximately 50% of practitioners treating men with testosterone therapy monitor estrogen levels.
• Use of aromatase inhibitors: Studies have shown that aromatase inhibitors, such as anastrozole, can be effective in reducing estradiol levels in men on testosterone therapy 3, 4, 5.
• Adjustment of testosterone dosage: The dosage of testosterone may need to be adjusted to minimize the elevation of estradiol levels.

Aromatase Inhibitors

Aromatase inhibitors, such as anastrozole, work by blocking the conversion of testosterone to estradiol.

• Efficacy: Studies have shown that anastrozole can effectively reduce estradiol levels in men on testosterone therapy 3, 4, 5.
• Dosage: The dosage of anastrozole can vary, but common starting doses range from 0.5 mg to 1 mg per day or week 3, 2.

Testosterone: Estradiol Ratio

The testosterone: estradiol ratio is an important consideration in men on testosterone therapy.

• Optimal ratio: While the optimal ratio has not been determined, a range of 10 to 30 has been suggested as potentially beneficial 6.
• Measurement: However, significant limitations exist in terms of steroid separation and measurement techniques, timing of samples, and lack of consistency from one assay to another 6.

Clinical Considerations

When managing elevated estradiol levels in men on testosterone therapy, several clinical considerations must be taken into account:

• Symptoms: Symptoms such as gynecomastia, erectile dysfunction, and mood changes can be associated with elevated estradiol levels 2.
• Monitoring: Regular monitoring of estradiol levels and adjustment of treatment as needed is crucial to minimize the risk of adverse effects 3, 2.
• Individualized treatment: Treatment should be individualized based on the patient's specific needs and response to therapy 3, 2.