Introduction to Exemestane


by Mike Arnold

Estrogen and the Bodybuilder

The human body is an incredibly complex and precise organism, capable of self-regulating all aspects of its internal environment down to the most minute level of functioning. Under normal circumstances this highly interconnected corporal collaboration runs effortlessly, with each system dependent on the next for physiological equilibrium, but this can all change when outside influences are brought into the equation.

As BB’rs and strength athletes, we deliberately seek to disrupt this delicate balance through the planned use of anabolic-androgenic steroids. While useful for helping us achieve our physique & strength goals, the subsequent alterations to our hormonal landscape can result in unwanted side effects.

One of the most frequently encountered is elevated estrogen; the hormone typically associated with womanhood and the development of female secondary sex characteristics. Although necessary for the development & proper functioning of both sexes, males require only small amounts of this hormone in order to meet physiological demand. When levels become excessive, a host of side effects can emerge ranging from gynecomastia, water retention, fat gain, increased blood pressure, sexual dysfunction, reduced libido, mood disturbances, and HPTA suppression, among others.

All steroids, once ingested, will eventually be metabolized (converted) into other metabolite(s). Some of them, due to their specific molecular structure, are incapable of converting into estrogen. These are known as non-aromatizable AAS and will not affect estrogen levels regardless of dosage. On the opposite end of the spectrum we have aromatizable AAS. These drugs convert into estrogen quite readily and can be problematic at even moderate dosages. The process by which a steroid converts into estrogen is known as aromatization. Aromatization takes place when a steroid molecule interacts with a naturally produced enzyme called aromatase.

Obviously, estrogen levels must be controlled if we want to avoid the aforementioned side effects. One option would be to simply eliminate aromatizable AAS from our repertoire of performance enhancing drugs, but this isn’t an acceptable solution for most, as these drugs comprise not only some of our most effective muscle building agents (think testosterone), but some estrogen is also desirable for both growth & health. For this reason, the goal should be to normalize estrogen levels, not eliminate it, thereby providing us with the best of both worlds. Fortunately, we do have one available option, which addresses the problem at its root by controlling the rate of aromatization.

Combating Aromatase

About 20 years ago, thanks to Big Pharma, BB’rs we introduced to a class of drugs known as aromatase inhibitors. As the only compounds capable of directly stopping the conversion of steroids into estrogen, BB’rs were able, for the first time, to use aromatizable AAS without the fear of estrogenic side effects. Previously, BB’rs were able to counteract some of these side effects, such as gynecomastia, through the use of the S.E.R.M. tamoxifen (Nolvadex). However, it was wholly ineffective at reducing systematic estrogen levels, which meant the BB’r was still prone to experiencing water retention, fat gain, sexual dysfunction, and a plethora of other estrogen related side effects.

The first aromatase inhibitor to be used by BB’rs was anastrozole (Arimidex). While it was certainly effective at bringing estrogen levels under control, it had its downside in the form of estrogen rebound. For those of you who are unaware, estrogen rebound is a term used to describe an abrupt rise in estrogen levels immediately following a period of estrogen suppression (this typically takes place after an A.I. has been discontinued, although certain anti-estrogenic steroids are sometimes to blame), but in order for us to understand how A.I.’s like Arimidex cause estrogen rebound, we must first lean how A.I.’s work to reduce estrogen levels in the first place.

As mentioned above, estrogen is produced by the body when an aromatizable steroid comes in contact with the aromatase enzyme. Essentially, aromatase inhibitors work by interfering with this basic step in estrogen synthesis. Here’s how it works. After being manufactured in the fat cell, aromatase is released into circulation, at which point it will float through the bloodstream until it either comes in contact with a substance it can attach to, or until its lives out the remainder of its life in an inert state. If it comes in contact with an aromatizable steroid, the steroid is converted into estrogen. However, by preventing aromatizable AAS from coming in contact with aromatase, conversion is unable to take place. That is where A.I’s come in.

Aromatase inhibitors don’t stop the production of aromatase, nor do they eliminate it from the body. Rather, they latch onto the aromatase molecule itself, which prevents it from being able to bind to AAS and exert its effects. But what if AAS reach the aromatase enzyme first? This is a good question, but a non-issue, as A.I.’s possess a stronger binding affinity for aromatase than steroids do, which means that aromatase actually prefers to bind with A.I.’s over steroids. As long as we dose our A.I. properly, we can circumvent the conversion process sufficiently enough to keep estrogen levels within a normal range.

In today’s market there are two types of aromatase inhibitors available to the general public; Class I and Class II, with each one being assigned a classification according to its duration of action. Class I A.I.’s, such as Arimidex, are only capable of binding to aromatase temporarily. As long as they continue to be administered, this is of no concern, but upon discontinuation all currently bound aromatase will be released back into circulation, resulting in an above normal amount of aromatase in the bloodstream and an increased estrogen conversion rate. This leaves the body susceptible to all the side effects typically encountered when exposed to elevated estrogen levels. On the other hand, Class 1 aromatase inhibitors (often referred to as suicide inhibitors) bind irreversibly to aromatase, causing permanent deactivation of the enzyme. This is a significant advantage, as it eliminates the possibility of experiencing estrogen rebound.
After the release of Arimidex, we witnessed the emergence of Letrozole. While more potent than its forerunner, it was also a Class II and by nature just as capable of causing estrogen rebound. It was not until exemestane (Aromasin) made its entrance that BB’rs had access to a full-fledged Class I A.I. with considerable potency. This made exemestane ideal for not only on-cycle use, but for use during PCT as well—a time when estrogen rebound can work directly against the goal of HPTA recovery.

Additional Benefits and Misconceptions

While A.I’s are normally employed in order to help mitigate the side effects of AAS, there seems to be a lesser degree of awareness regarding the ability of A.I.’s to cause side effects in their own right. Although the benefits often outweigh the risks, it should be noted that most A.I’s have a deleterious effect on the lipid profile, which can negatively impact cardiovascular health. When paired with lipid damaging AAS, the potential for harm is further amplified. With cardiovascular disease afflicting an ever-greater number of BB’rs this is something to take into consideration. As always, regular bloodwork paired with preventative action is a must.

If this put a sour taste in your mouth, I have good news for you. In contrast to most other A.I’s, exemestane appears to be exempt from this side effect. Clinical trials support this stance, with exemestane having demonstrated a neutral effect on both total cholesterol and HDL levels on multiple occasions. This alone will persuade some to make the switch to exemestane; probably a wise decision.

Estrogen management is also associated with certain cosmetic benefits via reduced water retention—namely an increase in muscle hardness and dryness. An improvement in these areas also tends to enhance separation and detail—important qualities for those who are about to enter a contest, or even for those who just want to look their best at the beach. These days, there is no reason for anyone to walk around looking bloated and water-logged due to estrogen over-load.

Over the last 10-15 years, some in the community have voiced concerns regarding the over-suppression of estrogen. These individuals believe that estrogen plays a vital role in the muscle growth process and that by using A.I’s, estrogen levels can drop into a less than optimal range, negating the positive effects estrogen has on muscle growth. Nothing could be further from the truth. While the “over-suppression” of estrogen can indeed have negative implications on muscle growth, research has clearly shown that A.I.’s such as letrozole, anastrozole, and exemestane, even when used at moderate-high dosages, do not reduce estrogen levels low enough to have this effect, especially when dosed reasonably.

In one clinical trial, designed specifically to examine the effects of A.I.’s in men, exemestane was used at a full 50 mg daily (a large dose by most standards). Even at this dose, it was only able to lower estrogen levels by about 60%. Letrozole, when used at 2 mg daily, reduced estrogen levels just under 60%, while Arimidex came in at around 47% when used at 1 mg daily (forgive me if my figures are slightly off, as it has been a few years since I read this study). So much for over-suppression. While anecdotal evidence has revealed that these AI’s are capable of lowering estrogen further than what was witnessed in this study, the fear is still un-founded, as one’s A.I. dose can be individually tailored to correspond to their own personal AAS program, effectively keeping estrogen levels within the normal range.

Others have also put forth the notion that excess estrogen levels are beneficial for muscle growth and that by using A.I.’s we are essentially short-changing ourselves of the gains we could be making. This belief originates from the more is better philosophy, but is based on the faulty assumption that estrogen functions in the same way as AAS. While AAS work on a dose-dependent basis (although not in linear fashion), there is no research to suggest that above-normal estrogen levels are anymore beneficial for muscle growth than those that fall within the normal range. However there has been research which suggests the opposite—that a normal amount of estrogen is all that is required in order to receive its full muscle-building benefits.

Adding additional credibility to this claim is the ability of A.I.’s to increase free testosterone. In the same way that A.I.’s bind to aromatase, rendering it inactive, up to 98% of all the testosterone in the human body is bound by SHBG. Of the small percentage that is available for use, a portion of it converts to both estrogen and DHT. By lowering the conversion rate to estrogen through A.I. usage, a larger percentage of testosterone remains metabolically active and able to attach to the androgen receptors where it can exert its muscle-building effects. This increase in free testosterone increases the muscle building capacity of testosterone, per mg injected (or any other aromatizable steroid).

Sourcing Issues

Unfortunately, many of the A.I.’s sold through peptide-research chem. companies, as well as those sold by UGL’s, are of poor quality, containing little to no active ingredient. This can be a big problem for those who depend on these products to keep their estrogen levels under control. In almost every case, unless the company selling these products does independent lab testing on each and every batch of every product they sell, it is impossible to ensure their purity & potency.

Three is a very good reason why pharmaceutical companies engage in such rigorous lab testing prior to offering their products up for sale—because it is the only way to be sure that the drug meets purity & potency standards. With some of these medications being necessary for the sustenance of life, even small mistakes can have potentially dire consequences. Thanks to the FDA (hey, at least they get some things right), pharmacies are required to submit their products to these testing procedures prior to sale, but grey-area companies, such as peptide-research chem. companies and UGL’s, are not. These are unregulated industries. Basically, they can run their business however they want, with little to no involvement from outside agencies.

As if that weren’t bad enough, most of these companies obtain their raw materials from sources which run—shall we say—shady operations, at least by comparison to the manufacturers which supply U.S. pharmacies. This makes regular 3rd party lab testing even more important for these companies. Sadly, few engage in lab-testing on the level necessary to ensure the type of product quality that most expect and which their hard-earned money demands. In fact, to my knowledge (I could be wrong), not a single research chem. company subjects every batch of every product they sell to this type of intensive lab-testing. Why? Because it cost a LOT of money, often times outweighing the cost of the products themselves!

When I was approached by Iron Mag Research to write an article on their exemestane product, there was no hesitation. While the company may be the new, the owners have been around for quite some time and have built a reputation for selling quality products. More importantly, I have known them for years and can personally attest to their character, as will others who know them. When they say they perform mass spec testing on each and every single batch of every product they sell, I believe them, and they have been more than willing to furnish these test results for my viewing. If you are looking for the highest quality, most reliable research chems on the market, I do not believe you are going to find better. If you think this is an advertisement for their exemestane, you are partially correct, but it is one I have no qualms with taking part in and either should you. This is a company that, at least as of this writing (and I don’t expect things to change), you can support without fear of getting ripped off or receiving low quality, half-ass products.