Rationale For The Use Of Aromasin

Rationale For The Use Of Aromasin With Tamoxifen During PCT

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Aromasin (Exemestane) is one of those weird compounds that nobody really knows
what to do with. What we generally hear about it makes it very
uninteresting…It’s a third generation Aromatase Inhibitor (AI) just like
Arimidex (Anastrozole) and Femera (Letrozole). Both of those two drugs are very
efficient at stopping the conversion of androgens into estrogen, and since we
have them, why bother with Aromasin? It’s a little harder to get than the other
two commonly used aromatase inhibitors, because it’s not in high demand, and
there’s never been a readily apparent advantage to using it. And I mean…lets
face it: It’s awkward-sounding. Aromasin doesn’t have much of a ring to it, and
exemestane is even worse. Arimidex has a bunch of cool abbreviations
(“A-dex” or just ‘dex) and even Letrozole is just “Letro”
to most people. Where’s the cool nickname for Aromasin/exemestane? A-Sin?
E-Stane? It just doesn’t work. It’s the black sheep of AIs. And why do we even
need it when we have Letrozole, which is by far the most efficient AI for
stopping aromatization (the process by which your body converts testosterone
into estrogen)? Letro can reduce estrogen levels by 98% or greater; clinically
a dose as low as 100mcgs has been shown to provide maximum aromatase inhibition

So why
would we need any other AIs? Well, first of all, estrogen is necessary for
healthy joints (3) as well as a healthy immune system (4). So getting rid of
98% of the estrogen in your body for an extended period of time may not be the
best of ideas. This may be useful on an extreme cutting cycle, leading up to a
bodybuilding contest, or if you are particularly prone to gyno, but certainly
can’t be used safely for extended periods of time without compromising your
joints and immune system.

That leaves us with Arimidex, which isn’t as potent as Letrozole, but at
.5mgs/day will still get rid of around half (50%) of the estrogen in your body.
Problem solved, right? Use Arimidex on your typical cycles, and if you are very
prone to gyno or are getting ready for a contest, use Letro.

But what about Post Cycle Therapy (PCT)?

I think at this point most people are sold on the use of Nolvadex (Tamoxifen
Citrate) instead of Clomid for post cycle therapy (PCT), since both compete
estrogen at the receptor site, both increase serum test levels, and both drugs
may also alter blood lipid profiles favorably (6). But since 20mgs of Tamoxifen
is equal to 150mgs of clomid for purposes of testosterone elevation, FSH and
LH, but Tamoxifen doesn’t decrease the LH response to LHRH (6) I think most
people agree to Nolvadex’s superiority for PCT.

Aromasin with Nolvadex

I’ve always been in favor of using Nolvadex during PCT, along with an AI, because
reducing estrogen levels has been positively correlated with an increase in
testosterone (7) so in my mind, it’s be beneficial to increase testosterone by
as many mechanisms as possible while trying to recover your endogenous
testosterone levels after a cycle. SO which AI do we use? Letro or A-dex? Well,
why don’t we just keep using whichever one we used during the cycle, and add in
some Nolvadex? Unfortunately, Nolvadex will significantly reduce the blood
plasma levels of both Letrozole as well as Arimidex (Cool. So if we choose to
use one of them with our Nolvadex on PCT, we’re throwing away a bit of money as
the Nolvadex will be reducing their effectiveness.

This, of course, is where Aromasin comes in, at 20-25mgs/day.

Aromasin, at that dose, will raise your testosterone levels 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. But what
about using it along with Nolvadex for PCT?

Difference Between Type-I and Type-II Aromatase Inhibitors

To understand why Aromasin may be useful in conjunction with Nolvadex while
both Letro and A-dex suffer reduced effectiveness, we’ll need to first
understand the differences between a Type-I and Type-II Aromatase Inhibitor.
Type I inhibitors (like Aromasin) are actually steroidal compounds, while type
II inhibitors (like Letro and A-dex) are non-steroidal drugs. Hence, androgenic
side effects are very possible with Type-I AIs, and they should probably be
avoided by women. Of course, there are some similarities between the two types
of AIs…both type I & type II AIs mimic normal substrates (essentially
androgens), allowing them to compete with the substrate for access to the
binding site on the aromatase enzyme. After this binding, the next step is
where things differ greatly for the two different types of AI’s. In the case of
a type-I AI, the noncompetitive inhibitor will bind, and the enzyme initiates a
sequence of hydroxylation; this hydroxylation produces an unbreakable covalent
bond between the inhibitor and the enzyme protein. Now, enzyme activity is
permanently blocked; even if all unattached inhibitor is removed. Aromatase
enzyme activity can only be restored by new enzyme synthesis. Now, on the other
hand, competitive inhibitors, called type II AI’s, reversibly bind to the
active enzyme site, and one of two things can happen: 1.) either no enzyme
activity is triggered or 2.) the enzyme is somehow triggered without effect.
The type II inhibitor can now actually disassociate from the binding site,
eventually allowing renewed competition between the inhibitor and the substrate
for binding to the site. This means that the effectiveness of competitive
aromatase inhibitors depends on the relative concentrations and affinities of
both the inhibitor and the substrate, while this is not so for noncompetitive
inhibitors. Aromasin is a type-I inhibitor, meaning that once it has done its
job, and deactivated the aromatase enzyme, we don’t need it anymore. Letrozole
and Arimidex actually need to remain present to continue their effects. This is
possibly why Nolvadex does not alter the pharmacokinetics of Aromasin (11).


Before we close the book on Aromasin, it’s worth noting that you can (and
should) still use one of the non-steroidal AIs during your cycle to reduce
estrogen, if necessary. When you are ready for PCT, you can then switch over to
Aromasin and still experience the full effects of an AI, since there is no
cross-over tolerance experienced between steroidal and non-steroidal AIs (9).
Since Aromasin is about 65% efficient at suppressing estrogen (10), it’s
certainly a very powerful agent, especially considering you won’t experience
reduced effectiveness because of your concurrent use of Nolvadex or from any
sort of tolerance developed by using other AIs on your cycle(9). There is also
a decent amount of preclinical data suggesting that Aromasin has a beneficial
effect on bone mineral metabolism that is not seen with non-steroidal agents,
and it may also have beneficial effects on lipid metabolism that are not found
in the non-steroidal Letro and A-dex (9).

Finally, as we’re going to be using Nolvadex for PCT anyway, and we ought to be
using an AI with it for maximum recovery…I think Aromasin- considering it’s
compatibility with Nolvadex and beneficial effects on bone mineral content and
lipid profile, has finally stopped being the black sheep of AIs and found a
home in our cycles.

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