What is the logic behind using anastrazole (aromatase inhibitor) with replacement testosterone (testosterone replacement therapy)?

From the Guidelines

Anastrozole is used alongside testosterone replacement therapy (TRT) to prevent excess testosterone from converting to estrogen, thereby minimizing the risk of estrogen-related side effects such as gynecomastia, water retention, and mood changes. When men receive TRT, some testosterone naturally converts to estrogen through an enzyme called aromatase. This conversion can lead to unwanted side effects. Anastrozole, typically prescribed at 0.5-1mg taken 1-2 times weekly during TRT, blocks the aromatase enzyme, maintaining proper hormone balance. The dose is adjusted based on blood test results showing testosterone and estradiol (estrogen) levels. This combination therapy is particularly useful for men who are "high aromatizers" or those experiencing estrogen-related side effects on TRT. However, it's essential not to completely eliminate estrogen, as men need some estrogen for bone health, cognitive function, and cardiovascular protection, as noted in studies such as 1. Regular monitoring of hormone levels is crucial to ensure proper dosing and to avoid complications from either excessive or insufficient estrogen levels. Some studies, like 1, have shown that anastrozole can increase the risk of certain side effects, such as vasomotor symptoms and musculoskeletal symptoms, but the benefits of using anastrozole with TRT often outweigh these risks. Key points to consider when using anastrozole with TRT include:

• Monitoring hormone levels regularly to adjust the dose of anastrozole
• Being aware of the potential side effects of anastrozole, such as hot flashes and joint pain
• Understanding the importance of maintaining some level of estrogen for overall health
• Adjusting the dose of anastrozole based on individual needs and response to treatment, as guided by studies like 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 and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

The logic behind using anastrazole (aromatase inhibitor) with replacement testosterone (testosterone replacement therapy) is to prevent the conversion of testosterone to estrogen via the aromatase enzyme, thereby minimizing the potential for estrogen-related side effects.

• Key points:
  • Anastrazole inhibits the aromatase enzyme, which converts androgens (like testosterone) to estrogens.
  • This inhibition reduces serum estradiol concentrations.
  • Testosterone replacement therapy can increase estrogen levels by providing a substrate for aromatization.
  • Co-administering anastrazole with testosterone replacement therapy can help maintain a balance between testosterone and estrogen levels 2

From the Research

Logic Behind Using Anastrazole with Replacement Testosterone

The logic behind using anastrazole (an aromatase inhibitor) with replacement testosterone (testosterone replacement therapy) can be understood through the following points:

• Purpose of Anastrazole: Anastrazole is used to inhibit the aromatase enzyme, which converts testosterone to estradiol (estrogen) in the body 3. By blocking this conversion, anastrazole helps maintain higher levels of testosterone and lower levels of estrogen.
• Testosterone Replacement Therapy (TRT): TRT is used to treat hypogonadism (low testosterone levels) in men. However, one of the side effects of TRT can be an increase in estrogen levels due to the aromatization of testosterone 4.
• Combining Anastrazole with TRT: The combination of anastrazole with TRT aims to mitigate the increase in estrogen levels associated with testosterone replacement. By inhibiting aromatase, anastrazole helps sustain therapeutic testosterone levels and reduces the frequency of testosterone injections or other forms of TRT 5.
• Benefits of Combination Therapy: Studies have shown that the use of anastrazole with TRT can lead to higher testosterone levels, lower estrogen levels, and a reduction in the frequency of testosterone injections 5, 4. This combination may also be beneficial for subfertile men with abnormal testosterone to estradiol ratios 6.

Key Findings from Studies

• A study published in 2014 found that men treated with testosterone pellets and anastrazole had significantly higher testosterone levels and lower estrogen levels compared to those treated with testosterone pellets alone 5.
• Another study from 2018 demonstrated the effectiveness of daily subcutaneous testosterone therapy combined with an aromatase inhibitor (anastrozole) in increasing testosterone levels and improving symptoms of testosterone deficiency 4.
• Research has also explored the use of anastrazole in adolescent boys with growth hormone deficiency, showing that it can decrease estrogen concentrations while allowing normal virilization 7.
• A 2022 study found that anastrozole treatment improved semen parameters and sex hormone levels in subfertile men, regardless of their testosterone to estradiol ratio 6.

Mechanism of Action

• Anastrazole works by selectively inhibiting the aromatase enzyme, which is responsible for converting androgens (like testosterone) into estrogens 3.
• By blocking this enzyme, anastrazole reduces the amount of estrogen produced in the body, which in turn can help increase testosterone levels and improve the efficacy of TRT.