Letrozole (FEMARA®) also refers to non-specific competitive inhibitors of aromatase. The chemical structure is benzgidrintriazola derivative 4, 4 ‘- [(1 H-1,2,4-triazo-1-yl-methylene) -dibenzonitril. Aromatase inhibitors such as letrozole act by competitive binding subunit of the enzyme – a gene of cytochrome P-450, the drug prevents the conversion of androgens to estrogens in adipose tissue, liver, skeletal muscle and decreases the concentration of the latter in the systemic circulation at 75-95% without significantly affecting synthesis in the adrenal corticosteroids and aldosterone, and thyroid hormones. Letrozole, according to different authors, blocks estrogen receptors in 50-75% of patients. Compared with anastrozole more pronounced (up to 98.8%) blocks the activity of cytochrome P-450 aromatase and significantly reduces the level of estrogen (estradiol, estrone, and estrone sulfate), however, the clinical significance of these data is uncertain.
The drug is available in tablets of 2.5 mg. For letrozole typical dose-response effect, so the dosage regimen should be clearly calculated. Applied per os is usually one tablet 1 time per day regardless of the meal, and then rapidly and completely absorbed in the digestive tract. The extent of absorption is independent of food intake. The equilibrium concentration in plasma is achieved in an average of 4 (2 to 6) weeks of application. The drug does not possess cumulative properties. Since blood plasma proteins, mainly albumin, binds about 60% of letrozole. And it penetrates into erythrocytes, where its concentration reaches 80% of the level in the blood. Letrozole is rapidly and uniformly distributed in the tissues. Metabolized preparation involving isozymes of cytochrome P-450 with a pharmacologically inactive metabolite carbinol (methanol-4,4′-bis-benzonitrile) and its ketone analog. The main route of elimination of letrozole from the body – through the urinary system. Not less than 75% of the administered dose excreted as glucuronide metabolite carbinol, and about 6% – as letrozole unaltered.
When initially expressed existing hepatic dysfunction (elevated liver transaminases), the drug should not be administered. Side effects usually are mild or moderate and similar to those in receipt of anastrozole. Also, 0.6-2% of the women taking the drug, there are bloody vaginal discharge, 1.7% – Leucorrhœa and sweating (1.1%), in a small part of the cases – shortness of breath; thrombophlebitis (0.6%) may develop. It should be noted that uncontrolled receiving letrozole bodybuilders often leads to coordination and promotes the dispersal of the violation.
Nonsteroidal aromatase blocker is a third generation vorozole. Compared with letrozole, it possesses almost identical influence on the levels of estrogen in the blood, but after 3 months after the beginning of reception resulted in a statistically significant increase in breast bone resorption markers in the blood serum of cancer patients. Moreover, 30% of women in the range from 1 to 6 months to three years and a significant reduction in recorded bone density. The most unfavorable of the side effects of this drug is set elevated levels of estrogen in the blood in excess of their reduction under the influence of aromatase blocking. It became clear that these changes are correlated with higher levels of bone resorption markers (Dowsett et. Al., 1999). In a small study in healthy menstruating women volunteers it was shown that vorozole a considerable (more than 74%) proportion of cases leads to the formation of ovarian cysts, ovarian hyperstimulation with pain and increased fluid secretion in Douglas space (Goss et. Al., 2004). So far, randomized trials of the effect of long-term use of this drug on the effectiveness of treatment and the incidence of osteoporosis is not carried out. Known data indicate the inadmissibility of the use of the drug in premenopausal women. The sports pharmacology it is also currently little used.
Representative steroidal aromatase ingbitorov third generation is exemestane, which, entering into covalent interaction with aromatase during the first cycle of oxidation leads to an effective selective irreversible inactivation of the enzyme reduces and estrogen synthesis in the body by 97%. Like anastrazole and letrozole, it is well tolerated by patients. Produced for receiving per os in form of tablets of 25 mg, and the daily dose is in the treatment of metastatic breast cancer in postmenopausal women. Exemestane, which is approved in the USA and is used as a drug in the oncology first-line endocrine therapy for breast cancer after receiving Imre class of drugs so far in the clinical setting has not been studied. However, it found that with respect to the process of accumulation and the extent of aromatization of estrogens it has an activity higher than tamoxifen, but less high than anastrozole (AS TO comparative study, 2002).
Clinical trials have shown that the metastatic breast cancer exemestane more pronounced compared to tamoxifen, slow disease progression, but does not affect the process of metastasis. Randomized MA-17, Research ATAS, IES showed that it differs from the spectrum of toxicity of non-steroidal aromatase inhibitor, but the therapeutic value of this data has not been studied. The drug is subjectively very well tolerated; the most common side effects are hot flushes (19%) and nausea (21%). According to the severity of impact on the development of osteoporosis and the incidence of pathological fractures in patients treated with exemestane, letrozole is not inferior. The risk of pathological fractures compared with the control group (placebo) for exemestane is increased by 60%! Arthralgia accompany the drug in 4.5% of cases, which is higher than that of tamoxifen (3.6%). However, the risk of endometrial cancer, as well as arterial and venous thrombosis significantly lower for exemestane (and also letrozole) than tamoxifen. The frequency of appearance of dryness and itching of the urogenital region when receiving exemestane above, and vaginal discharge – lower than tamoxifen.
Action exemestane on mental ability tests in the above MA-17, ATAS, the IES has not been studied. However, all taking anti-estrogen drugs, you should think about the fact that a lack of endogenous estrogen, even against the background replacement therapy significantly increases the risk of developing dementia in the future.
For the latest irreversible steroidal aromatase inhibitors character refers Ergo-pharm 6-OXO – structural analogue first generation drugs (3,6,17-androstentrion). Its action is similar to formestanom, but the effect on the increase in the level of testosterone in the blood expressed twice as strong. Efficiency for the clinic it has not yet been investigated. It is used in high doses the drug once a day in cycles of 4-6 weeks.
By aromatase inhibitors relates and the newly synthesized corporation MPR substance the T-Bomb II of , having the effect of a second messenger. T-Bomb II, due to the patented mechanism Optimone 5®, by activating the secretion of luteinizing hormone and simultaneously blocking SHBG (Sex Hormon Binding Globulin) – protein binding testosterone – and irreversible inactivation of aromatase, increases endogenous testosterone levels in the body 400%. The resulting substance T-Bomb II contains, besides SHBG, fatty acids, in particular, linoleic, linolenic, stearic and oleic. In addition, it comprises the amino acids glycine and L-arginine, Tribulus terrestris extract (Tr. Terrestris), other plant components, and mineral supplements in the form of magnesium oxide, zinc aspartate and copper gluconate. The mechanism of blocking aromatase, pharmacodynamics and pharmacokinetics of the substance is hardly explored, and preclinical and clinical trials to date, not finished.
On the pharmacological market for weight-lifters available product krizin (5,7-digidroksiflavon) that bodybuilders used in very high doses. It also has antiaromataznymi properties and is available in two forms – MRM-Chrysin, containing 500 mg per capsule of pure krizina and SciFit-Chrysin ES, containing half of the active substance. Descriptions of the side effects of the developers did not cause, but one should remember that all drugs and substances that have antiaromataznym action, can cause substantial harm to the body of an athlete and refer to the list of prohibited substances and methods.
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