Antitumor agent. It is a non-steroidal aromatase inhibitor – an enzyme with the participation of which occurs the synthesis of estrogen in women in the postmenopausal period. Aromatase promotes the conversion of androgens synthesized in the adrenal glands (primarily androstenedione and testosterone) into estrone and estradiol. Inhibition of aromatase activity is realized by competitive binding to the subunit of this enzyme – cytochrome P450 heme, which leads to a decrease in estrogen biosynthesis in all tissues, including the tissues of estrogen-dependent tumors.
Pharmacological action of the drug
Letrozole is rapidly and completely absorbed from the gastrointestinal tract, the average bioavailability is approximately 99.9%. Food intake slightly reduces the absorption rate. Mean time to reach Cmax of letrozole in blood is approximately 1 hour when letrozole is taken on an empty stomach and 2 hours when taken with food; mean Cmax value is approximately 129 ± 20.3 nmol/l when taken on an empty stomach and approximately 98.7 ± 18.6 nmol/l when taken with food, but the degree of letrozole absorption (when assessing AUC) is not changed.
The binding of letrozole to plasma proteins is approximately 60% (predominantly to albumin – 55%). The concentration of letrozole in erythrocytes is about 80% of that in blood plasma. The apparent Vd in equilibrium is approximately 1.87 ± 0.47 l/kg. Equilibrium concentration is reached within 2-6 weeks of daily dosing of 2.5 mg. Pharmacokinetics is non-linear.
No cumulation has been observed with long-term use. Letrozole is largely metabolized by CYP3A4 and CYP2A6 isoenzymes to form pharmacologically inactive carbinol compound. It is excreted mainly by the kidneys as metabolites, and to a lesser extent – through the intestine. T1/2 is approximately 48 hours.
Indications for taking the drug, the cycle with Litrozole
Early stages of invasive breast cancer, whose cells have receptors to hormones, in postmenopausal women, as adjuvant therapy. Early-stage invasive breast cancer in postmenopausal women after completion of standard adjuvant tamoxifen therapy for 5 years as extended adjuvant therapy. Disseminated hormone-dependent breast cancer in postmenopausal women (first-line therapy). Disseminated breast cancer in the development of relapse or disease progression in postmenopausal women (natural or artificially induced) who received prior therapy with anti-estrogens. Hormone-dependent HER-2 negative breast cancer in postmenopausal women as neoadjuvant therapy when chemotherapy is contraindicated and there is no need for emergency surgery.
Before the beginning of the treatment with the drug, it is recommended to study the estrogen receptor status of the body. The appropriateness of administration to patients without lymph node involvement is determined individually: the degree of malignancy, tumor size, the presence of estrogen receptors, age are taken into account. The drug dosage regimen does not need to be corrected in patients with liver and/or renal dysfunction (with a CKR greater than 10 ml/min). In patients with CKD less than 10 ml/min, the ratio of potential risk to expected benefit should be assessed.
No clinically significant changes in plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH and renin activity were observed in postmenopausal patients who were treated at a daily dose of 0.1-5 mg. ACTH stimulation test after 6 and 12 weeks of treatment at a daily dose of up to 5 mg showed no reduction in aldosterone or cortisol production. There is no need for GCS and ICS during treatment. Inhibition of estrogen synthesis during treatment with the drug does not result in the accumulation of androgen precursors. No changes in LH and FSH concentrations or thyroid function abnormalities have been observed during treatment with the drug. During the drug therapy, it is necessary to refrain from potentially hazardous activities that require increased attention, rapid motor and mental reactions (including driving or operating machinery).
The use of Letrozole, a drug used to promote the burning of fat, is becoming more popular. Some people take it on a cycle, while others take it before and after their cycle. There are pros and cons to taking Letrozole in either way. When you take Letrozole on a cycle, you are able to lose weight quickly. You also don’t have to worry about your body building up a tolerance to the drug. However, when you take it before and after your cycle, you may not lose as much weight as quickly, but you will be less likely to experience any negative side effects.
Letrozole drug cycle for beginners
Considering all the above-mentioned abilities of the drug, its popularity among athletes is quite understandable. When taking a course of anabolic substances designed to promote more intensive building of muscle mass, it is necessary to neutralize the side effects that inevitably accompany most steroids.
The following effects can be achieved through the use of Letrozole:
- Blocking the body’s production of estrogen;
- prevention of excess fluid, gynecomastia;
- normalization of blood pressure;
- Strengthening of muscles, promotion of muscle density;
- stimulation of the body’s own endogenous testosterone production;
- Increased endurance and recovery rate after workouts.
One of the additional effects of the product is its ability to stimulate spermatogenesis.
The product is recommended for use in bodybuilding by men. For women, it can be used as an adjunct in the treatment of cancer, endometriosis, infertility. However, most often Letrozol is prescribed by doctors after menopause. Letrozole and other IAs are already well established as drugs for the treatment of breast cancer, various estrogen-dependent gynecological diseases, drugs for the correction of hormonal status and fertility in men. However, lack of experience with their use and the side effects they have had are limiting factors in the use of these drugs for the treatment of infertility.
The available data show that letrozole is at least as effective (and most likely more effective) than CC for inducing ovulation and has a similar rate of live births. It is also important that it has some advantages over CC. Numerous studies have shown that letrozole can be as effective as gonadotropins, with advantages such as low cost and low rates of multiple pregnancies.
There is no doubt that the issue of the potential teratogenic effects of letrozole needs to be further addressed with large-scale studies. IAs, and in particular letrozole, deserve fair attention and evaluation, at least to be available in a research context to collect objective data regarding their efficacy and safety.