What is Letrozol
Letrozole, a potent third-generation reversible oral aromatase inhibitor (AI), is a widely used medication for the treatment of postmenopausal women with metastatic breast cancer. This treatment, usually given at a dose of 2.5-5.0 mg/day, achieves optimal suppression of serum estrogen levels and is almost devoid of side effects. The property of letrozole to effectively reduce estrogen levels can be used to temporarily level the effect of estrogen through a negative feedback mechanism on the hypothalamus and thus stimulate the secretion of follicle stimulating hormone (FSH).
When taken orally in doses of 1-5 mg/day letrozole and anastrozole reduce estrogen levels by 97-99%. Due to a significant decrease in circulating estrogen levels in peripheral blood, IAs are a promising therapy not only for estrogen-dependent diseases, but also their use in the early follicular phase of the menstrual cycle can increase the release of pituitary gonadotropic hormones, leading to follicular growth and ovulation in infertile patients. Although the use of letrozole as an ovulation inducer is widespread, it is still “off label.
Contents Letrozole 2.5 mg Excipients: lactose monohydrate 50 mg, sodium carboxymethyl starch 2.5 mg, colloidal silica 500 µg, microcrystalline cellulose 28 mg, crosspovidone 4 mg, pregelatinized corn starch 11.5 mg, magnesium stearate 1 mg. Film coating composition: opadray Y 1-7000 (hypromellose, titanium dioxide, macrogol (polyethylene glycol)) 3.73 mg, iron oxide yellow dye 270 µg. Antitumor drug, inhibitor of estrogen synthesis. Letrozole has anti-estrogenic effect, selectively inhibits aromatase (enzyme of estrogen synthesis) through highly specific competitive binding to the subunit of this enzyme – cytochrome P450 heme.
Benefits of the drug letrozole
The benefit of letrozole has been particularly evident when Her2 is overexpressed in the tumor simultaneously with high expression of ER; the use of Tam in such tumors produces almost no objective response. In addition, according to immunohistochemical analysis, IA was more pronounced than Tam in reducing the expression of the proliferative activity marker Ki67, indicating a more significant effect on the cell cycle. The question about the long-term results of neoadjuvant GT remains open. The average follow-up period in the P024 study is 4 years, so such results can be expected soon. However, as noted in an editorial in J Clin Oncol, studies of the effectiveness of neoadjuvant GT in breast cancer are of low power and require meta-analysis. It is relevant to search for markers (except hormone receptors) to predict tumor response to neoadjuvant GT using IA in the range of 80-90%, as well as markers to identify tumors in which CT is ineffective.
By determining the spectrum of such markers it would be possible to make real progress in creating a new standard of treatment through neoadjuvant GT. Currently such studies in neoadjuvant Femara are conducted within the framework of FAST projects (research of estrogen E1, E2, E1S levels in tumor), FEMARA (research of proliferation and apoptosis markers in tumor tissue), LETMA-2 (markers of response/resistance to Femara detected by multiplex analysis of tumor biopsies), FRAGRANCE (study of correlation of Her2, EGFR, Bcl-2, AIBI, MTA1s expression, aromatase levels and other biologically active proteins in tumor with the tumor response to neoadjuvant GT).
The information on the results of clinical trials of letrozole can be summarized as follows. Letrozole (Femara, Novartis Pharma Services AG) is the main (most widely studied and prescribed) IA, which is taken once daily, is currently available in more than 90 countries. In 57 countries, including EU member states and the US, Femara is approved for use in extended adjuvant therapy for early hormone-receptor-positive early hormone-receptor-positive breast cancer in postmenopausal patients who have completed the standard adjuvant therapy there.
Femara is also indicated as a first-line therapy for postmenopausal patients with receptor-positive or receptor-unknown locally advanced or metastatic breast cancer, as well as for the treatment of postmenopausal patients with advanced breast cancer when the disease has progressed after anti-estrogen therapy. There is evidence for the efficacy of neoadjuvant Femara in postmenopausal patients with hormone-receptor-positive breast cancer that do not meet the criteria for organ-sparing surgery.
Pharmacological effect of the drug
Antitumor drug, inhibitor of estrogen synthesis. Letrozole has anti-estrogenic effect, selectively inhibits aromatase (enzyme of estrogen synthesis) by a highly specific competitive binding to the subunit of this enzyme – cytochrome P450 heme. It blocks estrogen synthesis in both peripheral and tumor tissues. In postmenopausal women, estrogens are formed mainly with the participation of aromatase enzyme, which converts androgens synthesized in adrenal glands (primarily androstenedione and testosterone) into estrone and estradiol. Daily administration of Letrozole at a daily dose of 0.1-5 mg leads to a decrease in plasma concentrations of estradiol, estrone and estrone sulfate by 75-95% of baseline. Suppression of estrogen synthesis is maintained throughout the treatment period. When using Letrozole in dose range from 0.1 to 5 mg, no disturbance of steroid hormone synthesis in adrenal glands is observed, ACTH test reveals no disturbance of aldosterone or cortisol synthesis.
No additional administration of glucocorticoids and mineralocorticoids is required. Blockade of estrogen biosynthesis does not lead to accumulation of androgens, which are precursors of estrogens. No changes in plasma concentrations of LH and FSH, changes in thyroid function, changes in lipid profile, increased incidence of myocardial infarction and stroke have been observed during treatment with Letrozole. Against the background of Letrozole treatment there is a slight increase in the incidence of osteoporosis (6.9% compared to 5.5% against placebo).
However, the incidence of bone fractures in patients receiving Letrozole does not differ from that in healthy people of the same age. Adjuvant therapy with Letrozole for early-stage breast cancer reduces the risk of recurrence, increases survival without signs of disease for 5 years, and reduces the risk of developing secondary tumors. Prolonged adjuvant therapy with Letrozole reduces the risk of recurrence by 42%. A significant benefit in terms of symptom-free survival was observed in the letrozole group regardless of lymph node involvement. Letrozole treatment reduces mortality in patients with lymph node involvement by 40%.
Benefits and indications of Letrazole for women
Early stages of estrogen receptor-expressing breast cancer in postmenopausal women as adjuvant therapy;
Early-stage breast cancer in postmenopausal women after completion of standard adjuvant therapy with tamoxifen;
as extended adjuvant therapy;
common hormone-dependent breast cancer in postmenopausal women – first-line therapy;
Advanced breast cancer in postmenopausal women (natural or induced) who received prior anti-estrogen therapy.
When it comes to bodybuilding and weight loss drugs, one of the most popular options out there is Letrozole. This drug is known for its ability to help burn fat while preserving muscle mass, making it a great choice for those looking to get lean. Letrozole also has a number of other benefits that make it an attractive option for men looking to improve their health and physique. Here are some of the key benefits of taking Letrozole:
1) Increased Fat Burning – One of the main benefits of Letrozole is its ability to help burn fat. This drug works by blocking estrogen, which can help promote fat loss.
2) Preservation of Muscle Mass – Another benefit of Letrozole is that it helps preserve muscle mass. This is important, as preserving muscle mass can help you maintain your results over time.