Aromatase Inhibitors (AIs) Masterclass: Safely Controlling Estrogen (E2) Levels with Blood Work

The Aromatization Problem

When exogenous Testosterone Cypionate is introduced into the body, a percentage of it is converted into the primary female sex hormone, Estradiol (E2), via the Aromatase enzyme. This process, known as Aromatization, is natural, but high supraphysiological levels of T can lead to excessively high E2.

Aromatase Inhibitors (AIs) are prescription-only drugs used to block the action of this enzyme, thereby reducing the production of E2. They are a high-risk management tool and should never be used blindly without recent, high-sensitivity E2 blood testing.

Learn more about testosterone with our ultimate Canadian TRT guide

The E2 “Goldilocks” Principle: High vs. Low Estrogen

The goal is not to eliminate E2, but to keep it in a healthy, controlled range (the “Goldilocks” zone). Both high and low E2 levels are detrimental to health and well-being.

Symptoms of High E2 (Estrogen Dominance) 

High E2 signals your body to retain water and can increase blood pressure, but the most concerning risk is the development of breast tissue.

Symptoms of Low E2 (Estrogen Crash) 

Over-dosing an AI and crashing E2 is arguably more immediately debilitating than high E2.

The Two Main Classes of Aromatase Inhibitors

AIs fall into two pharmacological categories, and understanding the difference is essential for protocol stability.

1. Type I: Irreversible Steroidal AIs (Suicide Inhibitors)

• Example Drug: Exemestane (Aromasin)
• Mechanism: These drugs permanently bind to and destroy the Aromatase enzyme. The body must synthesize new Aromatase enzymes to restore function, making its effect highly predictable and long-lasting.
• Action: Causes a progressive, lasting drop in E2.
• Benefit: Less prone to rebound (a sudden spike in E2 when the drug is stopped) because the inhibition is permanent.
• Dosing Notes: Typically dosed every other day (EOD) or twice weekly, due to its lasting effect.

2. Type II: Reversible Non-Steroidal AIs

• Example Drug: Anastrozole (Arimidex)
• Mechanism: These drugs temporarily and reversibly block the active site of the Aromatase enzyme. Once the drug is metabolized, the Aromatase enzyme is free to function again.
• Action: Causes a sharper, shorter-lived drop in E2.
• Risk: Higher potential for Estrogen Rebound when the dose is suddenly stopped, as the previously blocked enzymes become active all at once.
• Dosing Notes: Typically requires daily (ED) or every-other-day (EOD) dosing to maintain inhibition.

Protocol: Dosing AIs Based on Blood Work

The greatest mistake made by users is taking a set AI dose (e.g., 0.5mg twice weekly) regardless of their actual E2 level. This is reckless and leads to E2 crashes.

Step 1: Get the Right Test 

You must use a High-Sensitivity Estradiol Assay (often labeled E2, LC-MS/MS). The standard test is inaccurate at male E2 levels and may give a false low reading. Refer to the guide: Blood Work Explained: Reading Your Total T, Free T, SHBG, and Lipid Panel

Step 2: Establish the E2 Range 

Your blood work should confirm your E2 is in the safe, mid-physiological range. For most men on exogenous T, this target is 20–40pg/mL (73-147pmol/L).

Step 3: Initiate Treatment Cautiously

• If E2 is High AND You Are Symptomatic (Gynecomastia, High BP): Begin with the lowest possible effective dose.
  • Anastrozole: Start at 0.25mg twice weekly (BIW) for two weeks.
  • Exemestane: Start at 6.25mg twice weekly (BIW) for two weeks.

Step 4: Re-Test and Adjust 

After starting the low dose, you must wait 10-14 days and then get a new E2 blood test.

The Takeaway: Dosage is based on E2 result, not a generic chart. If your E2 is in range and you have no symptoms, do not take an AI. The long-term risks of low E2 are more damaging than the short-term discomfort of mild high E2.