As I browse through the forums, I am seeing more and more that some are keeping their AI on-hand in case of gyno flare ups or other sides. The majority – I hope – is aware of the necessity of AI’s on cycle, but I wanted to address this for the lesser informed.

What is an AI?

An AI is an aromatase inhibitor. Aromatase is an enzyme whose sole responsibility is to synthesize estrogen hormones – estrone and estradiol – from androgens via a process called aromatization. Because our bodies are physiologically programmed to maintain a state of balance – homeostasis – aromatase enzymes are synthesized in response to elevated androgen levels. Therefore and in general, the higher the level of adrogens, the higher the level of aromatase enzymes. The higher the level of enzymes, the greater the potential for hyperestrogenism (excess estrogen). AI’s act to inhibit the activity of the enzyme, thereby providing regulation of estrogen levels.

High Estrogen Symptoms

• Fluid retention and weight gain
• Fluctuations in body temperature
• Elevated BP
• Adult acne
• Depression, apathy, irritability and aggression due to a hormonal imbalance
• Decrease libido or impotence
• Prostate issues (inflammation or cancer)
• Gyno

Why an AI

Taking into consideration that our androgen levels are well in excess while on cycle, the fact arises that the potential for excess estrogen dramatically increases. By allowing estrogen levels to rise uncontrollably, we are opening ourselves up to a host of symptoms associated with high estrogen. Outside of the risks of gyno, there is also the concern of sexual dysfunction. How many times do we see comments or reviews where a lesser experienced user is claiming bunk gear due to decreased of libido? Often times digging a little deeper into the cycle log or history of this individual, we will find an improper cycle and AI issues. Although some of the symptoms are minor, with gyno and libido issues being the greatest concern, there is no need IMO to experience any of these sides if they can be avoided. Considering that once you have gyno, the only way to get rid of it is through surgical removal, we should realize that these sides are much easier to prevent than they are to reverse. The AI’s main role here is to achieve greater hormonal balance and provide control for the user so as to avoid the occurrence of sides.

One aspect that I want to add to this is the effects estrogen has on the gonadotropins – LH & FSH. Studies have proven that estrogen provides negative feedback towards the synthesis and secretion of both LH & FSH. This is detrimental to the overall objective of PCT, which is to reboot natty systems. These gonadotropins main role here is to stimulate production of testosterone. If estrogen levels are elevated and left unchecked, outside of the listed side effects, the suppression of the gonadotropins will compromise the goal of PCT. Therefore, it is imperative that balance be achieved in order to not only prevent side effects but to also allow for a proper PCT and reset.

Types of AI’s

There are two types of AI’s:

• Type 1 (irreversible steroidal inhibitors)
• Type 2 (non-steroidal inhibitors)

Type 1 inhibitors form a permanent and deactivating bond with the aromatase enzyme, so it never lets go even when the drug is discontinued or its active life expires. Type 2 inhibitors inhibit the synthesis of estrogen via reversible competition for the aromatase enzyme, which means that it binds reversibly. An example of an irreversible inhibitor would be Aromasin (exemestane). Examples of reversible inhibitors, or Type 2, would be Letrozole (Femara) or Anastrozole (Arimidex).

Below is an excerpt from another thread that does a great job of explaining the two types and their modes of action:

Aromatase Inhibitors come in 2 types. Type 1 and Type 2. First Type 1 AI's bind by a process called hydroxylation; this hydroxylation process produces an unbreakable covalent bond between the inhibitor and the enzyme protein. Now the enzyme is permanently blocked even after all of the inhibitor is removed and can only be resumed by new enzyme synthesis. Type 2 Inhibitors on the other hand function all the same in their ability to reduce the binding process of the enzyme and the receptor. Except once the drug is discontinued or the concentration of the drug is sparse enough it is possible for the enzyme to seperate itself from the Inhibitor and eventually will allow renewed competion between the Inhibitor and the Enzyme for the receptor site. Aromasin is a type 1 AI and once it does what it's purpose is we don't need to continue use. Letro and Adex are Type 2 Ai's and the success of those drugs are continigent on the Doses and protocol of which we use them. Once you stop them you expose yourself to an Estrogen rebound. Now having said all of that there are also many other reason to why Aromasin use is beneficial to a Bodybuilder. One is Arimidex/Anastrozole Decreases IGF-1 18% while Aromasin/Exemestane Increases IGF-1 28%. Another is Aromasin is also known to decrease estrogen between 90-95% while boosting Endogenous Testosterone by about 60%, and also help out your free to bound testosterone ratio by lowering levels of Sex Hormone Binding Globulin (SHBG), by about 20% (12)…SHBG is that nasty enzyme that binds to testosterone and renders it useless for building muscle.

The above quoted paragraph's credit goes to CarlosDanger aka GS, who is IMHO the pct guru.

How much AI?

This answer can be tricky, because some degree of trial and error must take place to find your individual “sweet spot”. In order to do this, the following recommended doses should be administered during your cycle, and then blood tests must be run to determine where your estradiol levels are presently. This data will guide you in determining what, if any, tweaks are appropriate.

Aromasin: 12.5mg EOD
Arimidex: 0.25mg E3D
Letro: see below

My personal preference is Aromasin. Adex will suffice in terms of controlling enzyme activity during cycle. Because the bond Adex forms is reversible, it can cause the bound enzymes to become released and renew competition once the drug has been discontinued or its active life has expired. For this reason, IMO, Adex should be tapered off and Aromasin introduced leading into PCT. I am also more fanatical about ED dosing of Aromasin vs EOD. With a drug half-life of 27 hrs, a lower dose of 6.25mg ED would IMO yield a more stable and better sustained level. Once again, blood tests are a must for confirming the individuals “sweet spot”.
Letro, once again, should be used in the case of an emergency such as gyno flares. Because estrogen is active in the breast tissue during your gyno flares, eradication of the hormone will cause suppression of the symptom. With this in mind, you can and should expect to experience the symptoms of low estrogen (see below). The following is an excerpt from a conversation between I and someone about letro:

There's no particular concrete method to determining doses for Letro. Like the other AI's it really depends on how ur body responds to it. Tapering up to and maintaining a concentration at which I have had guys run is 2.5mg, maintaing that dose until u see relief of symptoms is key and after a week of relief u should begin to taper down. I recommend a daily administration. There is a great link where I found this protocol.
http://www.basskilleronline.com/gynoprevention.shtml

Now, keeping all of this in mind, I arrive at my final point:

TOO MUCH AI IS DETRIMENTAL AS WELL!!

The goal with incorporating an AI is to regulate the enzyme’s activity so as to avoid hyperestrogenism, not completely suppress it. Some estrogen is needed for normal physiological functions. Just like too much estrogen can lead to a host of side effects, so too can too little estrogen. Following the recommended dosages and running your blood work is key to achieving balance in this regard.

Low Estrogen Symptoms:

• Fatigue
• Weight gain
• Hot flashes and night sweats
• Depression, apathy, irritability and aggression due to a hormonal imbalance
• Elevated BP
• Insomnia or restless sleep
• Headaches
• Low libido or impotence
• Stiffness or joint pain
• Anxiety
• Heart palpitations
• Adult acne

UPDATE

For the longest time, we've preached a 27h half life for aromasin. We came to this conclusion based on case studies available to us at that time. These studies involved test subjects undergoing treatment for breast cancer (women).

Recent studies, however, have been showing a different half life for men. Below is an excerpt from one of these studies:

The terminal half-life in the present study (8.9 h) was considerably shorter than the published value of 27 h (23). The reason for this difference is not clear, but may be related to a true gender dependency possibly involving the volume of distribution (lower in males than females) and plasma or tissue protein binding (respectively, higher and lower in males). This finding may also be due to the lower sensitivity of the analytical methodology used in the previous studies (14 pg/ml by HPLC/RIA) (21).

The case study is from the Journal of Endocrinology and Metabolism and can be read here:

http://m.jcem.endojournals.org/content/88/12/5951.long