Anastrozole
Anastrozole (Arimidex)
Non-steroidal aromatase inhibitor. FDA-approved for breast cancer; used off-label on TRT to manage estradiol elevation. Only ~2.6% of men on TRT actually need it.
At a glance
- Half-life
- ~50 h ~50h (FDA PI). The long half-life is why dosing intervals for this compound are measured in days rather than hours.
- Routes
- Oral
- Evidence base
- 3 studies 2 human · 1 review
Mechanism
Reversible competitive inhibition of aromatase (CYP19A1), the enzyme that converts testosterone and androstenedione to estradiol in peripheral tissue. Dose-dependent reduction of serum E2: trial dosing in TRT patients produced a median E2 drop from 65 to 22 pg/mL. Accelerated BMD loss with long-term use (5-year ATAC data). AI-associated arthralgia driven by estradiol deprivation rather than direct drug toxicity. Does not affect testosterone, cortisol, or other steroidogenic pathways directly.
Dosing
Any amounts shown here are reported from published studies only. 2 of 3 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.
Where a study reports an amount, it appears in that study's entry below, attributed to the source.
Published evidence
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Human RCT 2008
Effect of anastrozole on bone mineral density: 5-year results from the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial
Accelerated BMD loss on anastrozole vs tamoxifen over 5 years: foundational evidence that AIs impact bone long-term.
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Human observational 2021
The utilization and impact of aromatase inhibitor therapy in men with elevated estradiol levels on testosterone therapy
In a single high-volume center over 14 years, only 2.6% of men on TRT met criteria for AI; those treated with 0.5mg 3x/week saw median E2 drop from 65 → 22 pg/mL.
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Review 2022
Aromatase inhibitor-associated musculoskeletal symptoms: clinical implications and potential mechanisms
Review of AI arthralgia mechanisms: estradiol deprivation is the primary driver. Relevant to both oncology and off-label male TRT contexts.
Reported side effects
- Arthralgia / joint pain
- Very common Moderate · ~36% in oncology trials; correlates with E2 suppression (<15-20 pg/mL) rather than anastrozole dose directly.
- Bone density loss (long-term)
- Common Serious · ATAC trial: accelerated BMD loss over 5 years vs tamoxifen. In men, E2 <15 pg/mL impairs bone remodeling. DEXA scan with long-term AI use.
- Crashed-E2 symptoms
- Common Moderate · Low libido, erectile dysfunction, fatigue, depression, lipid impairment when E2 drops below ~20 pg/mL. The single most common error on TRT AI management.
- Hot flashes
- Occasional Mild · More common in women on higher oncology doses. Less common in men on TRT micro-dosing.
- Lipid panel changes
- Occasional Mild · Estradiol is cardioprotective in men; excessive suppression can worsen HDL / triglyceride ratio. Monitor lipid panel with long-term use.
Storage
Oral tablets: room temperature, sealed container, away from moisture.