The Peptide Desk The Peptide Desk

This information is for research and educational purposes only. No medical recommendations. Products are not approved for human use. For health questions, consult a doctor.

Lexicon
PCT & hormone control

Letrozole (Femara)

The most potent aromatase inhibitor - strong enough for gyno reversal, easy to overdose.

1 min read 9 sources

To the product To the sources
White tablet bottle with the black TPD label for letrozole on a white podium, next to a blue three-armed 3D molecule model in a bright lab
Compound approved · in the USA since 1997Lab tested in the shop

Summary

At a glance

Sources checked on 26 Oct 2026

Aromatase inhibited
>99.1 %

Estrogen production in the whole body, in all 12 women, anastrozole 97.3%2

Estradiol in the blood
-87.8 %

after 6 weeks, estrone sulfate even -98.0%2

Live births in PCOS
27.5 %

750 women, with clomiphene 19.1%4

Half-life
~2 days

according to the US label (terminal elimination)6

  • Letrozole is a non-steroidal aromatase inhibitor. It binds the enzyme aromatase and so slows the conversion of androgens into estrogens.79
  • In a head-to-head comparison it suppressed estrogen production in the whole body more than anastrozole: by more than 99.1 percent in all 12 women, while estradiol in the blood fell by 87.8 percent.2
  • In breast cancer after menopause it lowered the risk of recurrence compared with tamoxifen (BIG 1-98, over 8,000 women) and after five years of tamoxifen compared with placebo (MA.17).13
  • In women with PCOS it led to ovulation more often and to more live births than clomiphene (27.5 against 19.1 percent).4
  • In the USA letrozole has been approved as a prescription tablet since 1997. Everything here is the state of research, not a recommendation.5
Profile

Updated June 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~3 days

Half-life ~3 days
After 6 days: 25 %
Day 3 · 50 %Day 6 · 25 %Day 9 · 12.5 %Day 15 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon. The lexicon gives 2 to 4 days, we calculate with the middle.

Class
Aromatase inhibitor

non-steroidal, reversible

Use
Oral

1-2x per week

Half-life
about 2-4 days
Status
Clinically approved

breast cancer

Sizes
2.5 mg

3 sizes in the shop

Contents 12 sections
  1. At a glance
  2. What is Letrozole?
  3. How it works
  4. Dosing
  5. What the research shows
  6. Research status
  7. Side effects
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

What is Letrozole?

Letrozole (brand name Femara) is the most potent of the non-steroidal aromatase inhibitors. It lowers estradiol even more strongly than anastrozole: in a head-to-head study estradiol in the blood fell by 87.8 percent (anastrozole 84.9 percent) and estrogen production in the whole body by more than 99 percent (Geisler et al., 2002). That strength is both advantage and risk: letrozole can reverse active gynecomastia, but also crashes estradiol too low quickly if you are not careful.

This information is for research and educational purposes only. No medical advice.

Comparison

Lowering or blocking estrogen

Compounds around estrogen, as described in the TPD lexicon. Tap a card to open its entry.

Aromatase inhibitor, non-steroidal Letrozole (Femara) Aromatase
Aromatase inhibitor, non-steroidal Arimidex (Anastrozole) Aromatase Aromatase inhibitor, steroidal Aromasin (Exemestane) Aromatase Estrogen receptor modulator Tamoxifen (Nolvadex) ERα Estrogen receptor modulator Clomid (Clomiphene) ERα

Aromatase inhibitors lower the production of estrogen, receptor modulators such as tamoxifen and clomiphene block its effect at the receptor. 72

How it works

Like anastrozole, letrozole binds aromatase reversibly, just much more strongly. The near-complete estradiol suppression makes it the choice when other AIs are not enough - for example with already visible gynecomastia you want to push back.

Where it acts

Where letrozole acts

Tap a point or a card. Colour = aromatase, grey = observed in studies.

  1. Blood

    Estradiol lowered by 87.8%, estrone sulfate by 98.0%2

    Aromatase
  2. Pituitary and ovary

    In PCOS ovulation in 61.7% of cycles, with clomiphene 48.3%4

    Observed in trials
  3. Bone

    More skeletal events than with tamoxifen, new osteoporosis 5.8% against 4.5% with placebo3

    Observed in trials
  4. Heart and blood lipids

    More cardiac events and raised cholesterol than with tamoxifen1

    Observed in trials

Targets in the ChEMBL database7

Compound CHEMBL1444: one recorded mechanism, Inhibitor, direct binding.

Aromatase (CYP19A1)
Gene
CYP19A1
UniProt
P11511
ChEMBL
CHEMBL1978
Action
Inhibitor, direct binding
Many transparent bubble-like cells, each holding a small blue three-armed molecule
Letrozole binds aromatase inside the cells. Symbolic image.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

What the research shows

The BIG 1-98 study (NEJM, 2005) compared letrozole with tamoxifen in postmenopausal breast cancer and showed significant superiority of letrozole in disease-free survival. That confirms the very strong estrogen lowering that makes letrozole so potent in research contexts.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

How much estrogens fell2

Reduction from baseline, 12 women, 6 weeks of each drug

Whole-body estrogen production2 Letrozole: more than 99.1% in all
Letrozole 99.1%
Anastrozole 97.3%
Estradiol (E2)2
Letrozole 87.8%
Anastrozole 84.9%
Estrone (E1)2
Letrozole 84.3%
Anastrozole 81.0%
Estrone sulfate2
Letrozole 98.0%
Anastrozole 93.5%

Postmenopausal women with breast cancer, both drugs in random order. For estrone and estrone sulfate letrozole was significantly stronger, for estradiol the difference was smaller.

Share free of recurrence13

Disease-free survival, estimated, in percent

BIG 1-98, after 5 years1 8,010 women, against tamoxifen
Letrozole 84.0%
Tamoxifen 81.4%
MA.17, after 4 years3 5,187 women after 5 years of tamoxifen
Letrozole 93.0%
Placebo 87.0%

In BIG 1-98 the risk of recurrence fell by 19 percent (hazard ratio 0.81) and the risk of distant recurrence by 27 percent. MA.17 was stopped early after the first interim analysis on the recommendation of the safety committee.

Letrozole against clomiphene in PCOS4

750 women, up to five cycles, in percent

Live birth4
Letrozole 27.5%
Clomiphene 19.1%
Ovulation per cycle4
Letrozole 61.7%
Clomiphene 48.3%
Twins per pregnancy4
Letrozole 3.4%
Clomiphene 7.4%

Pregnancy losses did not differ (31.8 against 29.1 percent). Major congenital anomalies: 4 with letrozole, 1 with clomiphene, no statistical difference.

Glass model of an ovary with a glowing orange egg cell in an incubator between petri dishes
Studies on breast cancer and on ovulation in PCOS. Symbolic image.

Research status

Where the research stands

Letrozole has been approved since 1997 and the registry lists about 900 trials with it. Here is a selection of large trials of letrozole itself, plus trials in men. As of 26 Oct 2026. 8

  1. Preclinical Inhibition of aromatase
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 8 trials, 8 completed
  5. Approval in the USA since 1997
12,067 participants in phase 3 Approved: in the USA letrozole has been marketed as a prescription tablet since 1997 (Drugs@FDA). ChEMBL lists phase 4 as the highest phase.5
Show all 9 phase 3 and 4 trials on a timelineHide timeline 9 completed 0 running 3 with results
Phase 3
Phase 4

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.

Side effects

  • Estradiol crash: the main risk - joint pain, libido loss, lethargy, poor sleep.
  • Lipids: very low estradiol worsens cholesterol markedly.
  • Bone density: relevant with long-term use.

Tolerability

Side effects compared

Two large studies with numbers on side effects: letrozole against clomiphene in PCOS and against placebo after breast cancer.

20 of 100 Letrozole
33 of 100 Clomiphene
Event LetrozoleClomiphene
Hot flushes4 20%33%
Fatigue4 22%15%
Dizziness4 12%8%
New osteoporosis diagnosis3 6%0%

In BIG 1-98 skeletal and cardiac events and raised cholesterol were more common with letrozole, thrombosis, endometrial cancer and bleeding with tamoxifen. In MA.17 hot flashes, joint and muscle pain were more common with letrozole.13

Storage

Store dry and protected from light. Out of reach of children.

Three white tablet bottles and a folded light blue towel on a white shelf
Dry and protected from light in the closed original container. Symbolic image.

Related

Related compounds

Same targets or a different path: all in the TPD lexicon.

Letrozole (Femara)
Arimidex (Anastrozole) Inhibits the same enzyme, somewhat weaker in comparison Aromasin (Exemestane) Aromatase inhibitor with a steroid structure Tamoxifen (Nolvadex) Comparator in BIG 1-98, blocks the receptor Clomid (Clomiphene) Comparator in the PCOS study Enclomiphene (Androxal) Receptor modulator, different path Estradiol Cypionate Estradiol itself, which letrozole lowers

FAQ

Common questions about Letrozole (Femara)

Short answers, each backed by the sources below.

Is letrozole approved?

Yes. In the USA letrozole has been approved as a prescription tablet since 25 July 1997 and ChEMBL lists phase 4 as the highest phase. The large studies concern breast cancer after menopause.571

How much does letrozole lower estrogens?

In a study with 12 women who took both drugs one after the other, letrozole suppressed whole-body estrogen production by more than 99.1 percent and anastrozole by 97.3 percent. Estradiol in the blood fell by 87.8 percent with letrozole and estrone sulfate by 98.0 percent.2

What did BIG 1-98 show?

Over 8,000 postmenopausal women with hormone-sensitive breast cancer received letrozole or tamoxifen. After five years an estimated 84.0 against 81.4 percent were free of recurrence and the risk of recurrence fell by 19 percent. In return skeletal and cardiac events as well as raised cholesterol were more common with letrozole.1

What is known in PCOS?

In a study of 750 women with PCOS trying to conceive letrozole led to a live birth more often than clomiphene (27.5 against 19.1 percent) and to ovulation more often. Hot flushes were more common with clomiphene, fatigue and dizziness with letrozole.4

What about bone and blood lipids?

Less estrogen means less protection for bone. In MA.17 5.8 percent on letrozole and 4.5 percent on placebo received a new osteoporosis diagnosis, the difference was not significant. In BIG 1-98 raised cholesterol was more common with letrozole.31

How long does letrozole stay in the body?

The US label gives a terminal elimination half-life of about 2 days. According to the label a steady level is only reached after 2 to 6 weeks of daily use.6

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Aromatase
Enzyme that converts androgens such as testosterone into estrogens, among other places in fat tissue.
Disease-free survival
Share of people living without recurrence and without new cancer after a given time.
Estradiol
The body's most potent estrogen. It acts on bone, vessels, brain and reproduction.
Gynecomastia
Enlargement of breast gland tissue in men, often from an excess of estrogen.
Half-life
Time until half of a substance in the blood has been broken down.
Hazard ratio
Ratio of the risk of two groups over time. 0.81 means 19 percent fewer events.
Non-steroidal
Without the steroid backbone of the hormones. Exemestane, by contrast, is a steroidal aromatase inhibitor.
PCOS
Polycystic ovary syndrome: hormonal disorder with rare or absent ovulation, a common cause of infertility.
Postmenopausal
After menopause. Estrogen then comes almost only from aromatase in tissues.

Evidence

Sources

Show all 9 sourcesHide sources 4 Studies1 Trial registry4 Database checked 26 Oct 2026

Studies

  1. BIG 1-98: letrozole against tamoxifen in postmenopausal breast cancer

    BIG 1-98 Collaborative Group (Thürlimann et al.), New England Journal of Medicine, 2005

    DOI 10.1056/NEJMoa052258 PMID 16382061 NCT00004205
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Letrozole and anastrozole: estrogen production and levels compared

    Geisler et al., Journal of Clinical Oncology, 2002

    DOI 10.1200/JCO.2002.20.3.751 PMID 11821457
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. MA.17: letrozole after five years of tamoxifen

    Goss et al., New England Journal of Medicine, 2003

    DOI 10.1056/NEJMoa032312 PMID 14551341 NCT00003140
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Letrozole against clomiphene for infertility in PCOS

    Legro et al., New England Journal of Medicine, 2014

    DOI 10.1056/NEJMoa1313517 PMID 25006718 NCT00719186
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)

Trial registry

  1. Trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US approval (NDA 020726), prescription

    Drugs@FDA, U.S. Food and Drug Administration

    Checked 26 Oct 2026 via openFDA-API
  2. US label for letrozole (pharmacokinetics)

    DailyMed, U.S. National Library of Medicine

    Checked 26 Oct 2026 via openFDA-API, DailyMed
  3. Mechanism and approval in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL1444)

    Checked 26 Oct 2026 via ChEMBL
  4. Structure of letrozole in PubChem

    PubChem, U.S. National Library of Medicine (CID 3902)

    Checked 26 Oct 2026 via PubChem

In the shop

Letrozole (Femara) in the catalog

Sizes, prices and shipping times are on the product page.

To the product