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Letrozole

Hormone Management
FemaraNon-steroidal AI

Overview

Letrozole is a synthetic non-steroidal aromatase inhibitor, commonly known by its brand name Femara. It is not an endogenous hormone but a pharmaceutical compound designed to inhibit the aromatase enzyme. Letrozole belongs to the chemical class of triazoles and is primarily produced in a laboratory setting for therapeutic use. Researchers have extensively studied its role in hormone management, particularly in the context of breast cancer treatment. Letrozole's primary physiological role is to reduce estrogen production by inhibiting the aromatase enzyme, which converts androgens to estrogens. This reduction in estrogen levels is particularly beneficial in estrogen receptor-positive breast cancer, where the growth of cancer cells is fueled by estrogen. Researchers have also explored its use in fertility treatments and other hormone-related conditions. The mechanism of action of letrozole involves the inhibition of the aromatase enzyme, which is responsible for the biosynthesis of estrogens from androgen precursors. By blocking this enzyme, letrozole effectively reduces estrogen levels in the body, leading to decreased stimulation of estrogen receptors in estrogen-dependent tissues. This mechanism is crucial in slowing the growth of estrogen-dependent tumors. Letrozole is well-absorbed orally, with a bioavailability of approximately 99.9%. It has a relatively long half-life of about 2 days, allowing for once-daily dosing. The drug is metabolized primarily in the liver, with its metabolites excreted via the kidneys. Researchers have found that letrozole is extensively used in the clinical management of hormone receptor-positive breast cancer in postmenopausal women. It is approved by regulatory agencies such as the FDA for this indication. Its use is generally well-tolerated, although it requires careful monitoring due to potential side effects such as bone density reduction. Letrozole is a prescription-only medication, reflecting its potent effects and the need for medical supervision during treatment.

Mechanism of Action

Letrozole acts by inhibiting the aromatase enzyme, which is crucial in the conversion of androgens to estrogens. This inhibition leads to a significant reduction in circulating estrogen levels, thereby decreasing the stimulation of estrogen receptors in hormone-dependent tissues, such as certain breast cancers.

Molecular Data

FormulaC17H11N5
Molecular Weight285.3 g/mol
CAS Number112809-51-5
PubChem CID3902

Half-Life & Pharmacokinetics

OralApproximately 2 days

Letrozole is primarily administered orally, and its long half-life supports once-daily dosing.

Storage

Temperature

Store at room temperature (15-30°C)

Light

Protect from light

Form

Tablets are stable under recommended storage conditions

Notes

Keep in original packaging to protect from moisture.

Solubility

Letrozole is sparingly soluble in water but more soluble in organic solvents like ethanol.

Legal Status

🇩🇪DE

Prescription-only medication (verschreibungspflichtig).

🇺🇸US

FDA-approved for the treatment of hormone receptor-positive breast cancer; prescription required.

🇦🇺AU

TGA Schedule 4 (S4) prescription-only medicine.

🇬🇧UK

Prescription-only medicine (POM) as classified by the MHRA.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

8 Research Publications

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Meta-Analysis

The Cochrane database of systematic reviews · 2022

Researchers found that letrozole, an aromatase inhibitor, is more effective than clomiphene citrate for helping women with polycystic ovary syndrome (PCOS) conceive. The study showed higher live birth rates with letrozole, while the rates of ovarian hyperstimulation syndrome, miscarriage, and multiple pregnancies were similar between the two treatments.

  • Letrozole improves live birth rates compared to clomiphene citrate.
  • Ovarian hyperstimulation syndrome rates are similar for both treatments.
  • No significant difference in miscarriage or multiple pregnancy rates.
PubMed

Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.

Human

The New England journal of medicine · 2022

Researchers found that adding ribociclib to letrozole significantly improved overall survival in postmenopausal women with advanced breast cancer compared to letrozole alone. Patients receiving ribociclib lived, on average, over 12 months longer than those on placebo. The study confirmed the safety of this treatment combination.

  • Ribociclib plus letrozole increased median overall survival to 63.9 months.
  • The placebo group had a median overall survival of 51.4 months.
  • No new safety concerns were identified with ribociclib treatment.
PubMed

Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial.

Human

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2021

Researchers found that letrozole is more effective than clomiphene citrate for helping women with polycystic ovarian syndrome (PCOS) ovulate and achieve pregnancy. The study showed higher pregnancy rates and shorter time to conception with letrozole, along with a lower chance of multiple pregnancies due to better single follicle development.

  • Letrozole resulted in a pregnancy rate of 42.2% compared to 20.0% for clomiphene citrate.
  • Time to achieve pregnancy was shorter with letrozole (9.65 weeks) than with clomiphene citrate (11.07 weeks).
  • Letrozole led to higher rates of single follicle development (68.4%) compared to clomiphene citrate (44.8%).
PubMed

Letrozole for Female Infertility.

Review

Frontiers in endocrinology · 2021

Researchers observed that letrozole, a medication that inhibits estrogen production, has been effectively used for over 20 years to help women with infertility. The review highlights its safety and efficacy, while also raising questions about optimizing its use in treating female infertility.

  • Letrozole has been used for over 20 years in infertility treatments.
  • It effectively helps induce ovulation in women.
  • The review discusses potential improvements in its application.
PubMed

Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18).

Human

Breast cancer research and treatment · 2020

Researchers observed that combining palbociclib with letrozole did not significantly improve overall survival compared to letrozole alone in postmenopausal women with advanced breast cancer. However, the combination treatment did extend the time before patients needed subsequent chemotherapy. The most common side effect reported was a decrease in white blood cells.

  • Palbociclib plus letrozole did not significantly improve overall survival compared to letrozole alone.
  • The combination treatment extended the time before subsequent chemotherapy was needed.
  • The most common side effect was neutropenia, affecting 75% of patients.
PubMed

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

Human

Breast cancer research and treatment · 2019

Researchers found that the combination of palbociclib and letrozole significantly extended the time patients with advanced breast cancer lived without disease progression compared to letrozole alone, with a median progression-free survival of 27.6 months versus 14.5 months. This benefit was consistent across all patient groups, and the treatment was well-tolerated, maintaining patients' quality of life.

  • Palbociclib plus letrozole improved progression-free survival to 27.6 months.
  • The treatment delayed the need for chemotherapy compared to the placebo group.
  • Safety and quality of life remained favorable for patients receiving palbociclib.
PubMed

Palbociclib and Letrozole in Advanced Breast Cancer.

Human

The New England journal of medicine · 2016

Researchers found that combining palbociclib with letrozole significantly extended the time before disease progression in postmenopausal women with advanced breast cancer compared to letrozole alone. However, this combination treatment also led to higher rates of certain side effects, such as low blood cell counts.

  • Palbociclib plus letrozole increased progression-free survival to 24.8 months compared to 14.5 months with letrozole alone.
  • Common serious side effects included low white blood cell counts and anemia in the palbociclib group.
  • 9.7% of patients on palbociclib discontinued treatment due to side effects.
PubMed

Letrozole.

Review

Expert opinion on drug metabolism & toxicology · 2010

Researchers observed that letrozole, an aromatase inhibitor, is an effective and well-tolerated treatment for metastatic breast cancer in postmenopausal women. The drug has also shown promise in early breast cancer settings, both as an adjuvant and neoadjuvant treatment. Future research may explore combining letrozole with new therapies and personalizing treatment based on genetic factors.

  • Letrozole is effective for metastatic breast cancer in postmenopausal women.
  • It has confirmed efficacy in early breast cancer as both adjuvant and neoadjuvant treatment.
  • Future studies may focus on combining letrozole with new biologic agents and tailoring treatments.
PubMed

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This page is for informational and research purposes only. All information is based on published scientific literature. Nothing on this page constitutes medical advice or replaces consultation with a qualified healthcare professional.