Letrozole
Letro · Femara
Potent non-steroidal AI; highest estrogen suppression of the three common AIs.
Key takeaways
- Most potent of the three common aromatase inhibitors; label dosing suppresses estrogen by over 95%.
- ~99% oral bioavailability, ~33-hour half-life; suppression builds over the first weeks of dosing.
- Over-suppression is the main hazard in men: joint pain, libido loss, lipids, mood.
- Oncology use is trial-backed; off-label estradiol management on testosterone is not.
Reported dosing protocols
Protocols reported in research literature and clinic/community use — informational context, not a dosing recommendation.
| Use case | Dose | Route | Frequency | Duration |
|---|---|---|---|---|
| Breast cancer (label) | 2.5 mg | Oral | Once daily | Years (adjuvant) |
| Estradiol control (community) | 0.625–1.25 mg | Oral | 1–2× weekly | Symptom-driven |
Pharmacokinetic summary
- Model tier
- Advanced (t½ + Cmax + Tmax + F)
- Half-life
- 33.3 hours
- Cmax
- 45.684 ng/mL
- Tmax
- 0.1 days
- Bioavailability
- 99%
- Typical dose
- 0.625–2.5 mg
Frequently asked questions
Letrozole vs anastrozole — what's the practical difference?
Both are reversible non-steroidal AIs; letrozole suppresses estrogen more deeply at label doses (over 95% vs roughly 85–90%). That potency makes it effective for stubborn symptoms but much easier to overshoot into crashed estradiol.
What does crashed estradiol feel like?
Joint pain and stiffness, flat mood or irritability, lost libido, dry eyes and skin, and poor sleep are the classic cluster. The fix is stopping or back-titrating the AI and retesting estradiol, not adding anything else.
Is letrozole reversible?
Yes. It binds aromatase competitively and reversibly, unlike exemestane which permanently inactivates the enzyme. Estradiol recovers as the drug clears, typically over days to a couple of weeks depending on dose and duration.
References
- PubMed letrozole PK
- Letrozole comparative bioavailability study (Arzneimittel-Forschung 2005) — Human PK and bioavailability data in healthy subjects.
Related compounds
Arimidex (Anastrozole)
Non-steroidal aromatase inhibitor; used to control estradiol on-cycle. Over-suppression risk.
Aromasin (Exemestane)
Steroidal (suicidal) aromatase inhibitor; permanently inactivates aromatase enzyme.
Estradiol Topical (EstroGel)
Transdermal estradiol for feminizing HRT. Steady low-level delivery.
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