by Anthony Roberts -- 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 (2)! 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.
So 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 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.
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 (8). 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?
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 typeII 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 normalsubstrates (essentially
androgens), allowing them to compete with the substrate for accessto the binding site on the aromatase enzyme. After this binding,
thenext step is where things differ greatly for the two
different types of AI’s. In the case of a type-I AI, the noncompetitive
inhibitorwill bind, and the enzyme initiates a sequence of
hydroxylation; this hydroxylation produces an unbreakable covalent bond
betweenthe 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 substratefor binding to the site. This
means that the effectiveness of competitive aromatase inhibitors depends
on the relative concentrations and affinitiesof 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 isnot seen with
non-steroidal agents, and it may also have beneficial effects on lipid
metabolism that are notfound 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.
