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The Chemistry and Usage of Letrozole

Letrozole is an anti-estrogen that is used to widely to treat breast cancer, and is hormonally responsive after surgery. The World Heath Organization has assigned the trade name Femara as Letrozole’s International Nonproprietary Name.  

Anti-estrogens are broadly divided into two categories - the Selective Estrogen Receptor Modulators, popularly known as the SERMS and the Aromatase Inhibitors or the AIs. Letrozoles belong to the second category of anti-estrogens, the aromatase inhibitors. Drugs like Nolvadex and Clomid on the other hand fall in the category of SERMS.

The difference between EIs and SERMs

LetrozoleAt this point, it is important to understand the difference between how Selective Estrogen Receptor Modulators and Aromatase Inhibitors function. One rumor particularly common place is that SERMs, since they are essentially anti-estrogens, reduce circulating estrogen levels in blood.

This is however not the truth. SERMs do not reduce estrogen levels in blood; they only alter its effects. The lowering of estrogen levels is done by the second category of anti-estrogens; the aromatase inhibitors (EI).

SERMs, in general, only impede Estrogen’s action in breast tissue. They prevent Estrogens from binding at receptor sites by occupying the sites themselves. Estrogens are unable to break the strong bond with which SERMs bind to the receptor sites. This prevents estrogens from working their effects on the breast tissue. Gynecomastia does not formulate at the receptor cells since estrogens are not attached to the receptor sites and cannot trigger gene transcription in those cells. SERMs also forcibly occupy the receptor sites already taken up by estrogens, causing the same end result – inhibition of estrogen’s action on the breast tissue.

Aromatase inhibitors on the other hand effectively reduce the levels of estrogen in blood.

An introduction to Letrozoles

Letrozoles are non suicidal Aromatase Inhibitors, belonging to the third generation of aromatase inhibitors. They are administered orally and hold the approval of the Food and Drug Administration of the United States (FDA) for use in treating two particular kinds of breast cancer. One is the case when hormone receptor positive breast cancer develops locally or is contracted through metastatis. The other is a similar case but when the cancer is of the estrogen receptor unknown category.

The estrogen receptor unknown category refers to those breast cancer conditions where the role of estrogens can not be determined with certainty. In these cases, it is impossible to predict if estrogen caused the cancer in the first place or if it would complicate and worsen the cancer further. Letrozoles are used in the treatment of such cancer conditions in post menopausal women. It is however rare that Letrozole be required for treating the post menopausal estrogen receptor unknown cancer, first-line. In most cases, it is used only after the usual first-line treatments using Selective Estrogen Receptor Modulator drugs like the Nolvadex have failed to show any positive effects.

Arimidex, Letrozole and Aromasin together comprise the triad of popular aromatase inhibitor type of anti-estrogens. The three show similar characteristic and share similar uses. However what differentiates Letrozole from the other two aromatase inhibitors is its use in the treatment of the estrogen receptor unknown cancer specifically. Arimidex and Aromasin are used for treating post menopausal cancer in women but not the estrogen receptor unknown cancer specially.

The history of Letrozole and its usage in the anabolic steroid using community

Post its approval by the FDA for use in America, Letrozole was manufactured by Novartis industrially in 1997. The trademark names used for sale were Femara and Femar. While the name Femar was used in some countries in Europe, Femara found a more widespread global usage. This drug had been manufactured after the Arimidex and quickly became popular in the medical community. Even today, after the manufacture of Aromasin, Letrozole remains the strongest and most effective aromatase iInhibitor in use.

Letrozole HIstoryIts popularity grew such that Letrozole can now be easily found as itself or under the name Femara in over seventy countries all around the world. Additionally, several other brand names have been developed for Letrozole in the recent years.

In the course of time, Letrozole also gained popularity among the athlete and body building crowd as well as other gym enthusiasts who regularly use anabolic steroids.

Anabolic steroids which are aromatizable, like Dianabol and Equipoise are frequently used for their performance enhancing benefits among the body builders and athletes. The use of these steroids however leads to several side effects arising due to the excess of estrogen buildup in the body. Letrozole, being an aromatase inhibitor, helps lower the estrogen levels in blood and thus relieves anabolic steroid using individuals from side effects like gynecomastia, bloating and high blood pressure to name a few.

Additionally, Letrozole may also trigger the production and secretion of Testosterone in men and is therefore sometimes used in treatments during the Post Cycle Therapy phase after their anabolic steroid cycle ends.

Effectiveness of Letrozole as an anti-estrogen

According to the research paper “Aromatase inhibitors in advanced breast cancer” by HT. Mouridsen from the Department of Oncolgy, Letrozole performs best when compared to the other two aromatase inhibitors, in controlling the level of estrogen in the blood. The information pamphlets that are handed out with Letrozoles in pharmacies note that a 2.5mg of Letrozole when administered orally reduces the blood estrogen level by seventy eight percent on an average.

There have been other studies like the “Aromatase Inhibition: Translation Into A Successful Therapeutic Approach” by J Geisler and P.E. Lonning, where as much as 98 percent reduction in the circulating estrogen levels was observed. Its high efficiency is one reason why the Letrozole is used only when treatments with SERMs and other first line treatments turn out to be ineffective. This is also the reason why Letrozole is given only to women who are not of the child bearing age.

Mechanism of action

The aromatase enzyme help produce estrogens by converting androgens. Letrozole is a non suicidal and non steroidal aromatase inhibitor, which means it engages in competitive binding with the receptor site. The bound is made at the heme of the P450 cytochrome unit of the aromatase and even thought reversible; it strongly inhibits the production of estrogens by the aromatase in question.

Its mechanism of action is very diffireent from its peer Aromasin which, unlike Letrozole, is suicidal and steroidal. A suicidal and steroidal Aromatase Inhibitor binds permanently to the aromatase enzymes by trick. Such aromatase inhibitors posses a chemical structure which resembles the structure of aromatase enzyme’s usual binding targets. When the enzyme binds with the inhibitor, it is rendered effect less and can not produce any more estrogen.

Dosage information for anabolic steroid users

The primary use of Letrozole for athletes and body builders is not performance enhancement but inhibition and combating of the side effects of excessive estrogen in the body. For controlling estrogen during a cycle, the optimum dosage varies from anywhere between 1.25 to 2.5mg daily. These are just rough figures however since the optimum dosage will depend on the amount of anabloic steroids used by the individual as well as his sensitivity to aromatase inhibitors. It is important to note that Letrozole be administered to women who are post menopausal only.

Side effects of Letrozole

Side effects which are most common to Letrozole are joint pain, hot flashes, excessive sweating and fatigue. These side effects in most individuals are accompanied by signs and symptoms of hypoestrogenism. Long-term use of this drug may also lead to osteoporosis in some women.