Anti-Estrogens Report Card
By J @ AG-GUYS
Remember when you were in school, and you got a report card?
If you were like me, you dreaded that time of the semester. I
typically got passing grades and on occasion a failing grade
that would mean I had to pull straight A’s for the next half
of the year in order to avoid repeating a class. What does
this have to do with anything?
Well I was trying to figure out a way to rate the most
commonly used anti-estrogens on the market, and the best way I
can think of is to do a report card for them. Why a report
card? Well…because it’s pretty easy to understand, first of
all. You can be in first place in a race and that’s good, but
“1st” on a scale of 1-10 is bad…so lets ditch the
number system. I mean…hell…we all know what an “A+” is (or at
least, in theory we do), and if you’re anything like me, you
certainly know what an “F” is also. So I’m going to rate the
most popular anti-estrogens that are available on the market
today, with the all-too-familiar school grading system of A -
F.
Also, I’d like to state right off the bat that I’m going to
mainly be addressing the most commonly discussed and used
ancillary compounds on the market today, for use during a
cycle. Basically, if you can easily obtain it, you’ll be
reading about it in this piece. Sooo….that means if you’re
“old school” and are looking for a detailed description of
Cytadren or Teslac, you’re out of luck.
So why do we need anti-estrogens? Well, certain anabolic
steroids convert to estrogen - this is via the aromatase
enzyme, and is called aromatization. This is probably the
cause of most of the side effects we experience like bloating,
gynocomastia, (possibly) acne, and a host of other side
effects we’d rather avoid. Estrogen can also cause additional
growth, however, as well as having immunostimulating effects
and is beneficial for healthy joints- so it’s important to
note that we don’t want to eliminate all estrogen from our
bodies.
Anyway, before I get into it, I’m going to have to
explain a bit about different types of Anti-Estrogens, ok?
First we’ll take a look at SERMs, which stands for “Selective
Estrogen Receptor Inhibitor.” There are basically two drugs
in this class that we’re going to look at, namely Clomid (Clomiphene
Citrate) and Nolvadex (Tamoxifin Citrate).
Basically both of these drugs have the ability to act as an
estrogen agonist (or activator, in simpler- though less
precise- terms) in some tissue and as an antagonist (inactivator),
in others. I’ll get into the specific actions of both of them
shortly.
The other class of medications I’m going to explain is
Aromatase Inhibitors. Aromatase Inhibitors basically prevent
the aromatase enzyme from doing its job.
AIs are
classified into two types:
type I,
also known as suicidal or noncompetitive
inhibitors; and type II, known as competitive inhibitors.
Aromasin and ATD are in the first category, while Arimidex and
Letrozole are in the second. Both type I & II mimic substrates
(essentially androgens), and can compete with it for access
to the binding site on the actual enzyme (aromatase).
After this initial binding, the next step is where
things begin to differ for the two different types of AI’s.
Once a noncompetitive inhibitor has bound, the
enzyme initiates a sequence of what’s called hydroxylation,
and hydroxylation produces an unbreakable covalent bond
between the inhibitor and the enzyme protein. This
is important because now, enzyme (aromatase) activity is
permanently blocked; even if all of the unattached inhibitor
is removed, and now, enzyme activity can only be
restored by new enzyme synthesis. Type II AI’s or competitive
inhibitors, on the other hand, reversibly bind to the active
enzyme site, and one of two effects is had: no
enzyme activity is triggered, or the enzyme is somehow
triggered without effect. The type II inhibitor can
then actually disassociate from the enzyme, eventually
allowing renewed competition between the inhibitor and the
substrate for binding to the site (estrogen
synthesis).
Now that
SERMs have been explained as well as AI’s, we can see how each
of them rates on my “on-cycle report card.”
Clomid
Clomid is a drug given to women as a fertility aid, which acts
by binding to the estrogen receptor and thereby blocking
estrogen from doing the same in some tissues. It can bind to
breast tissue, and prevent estrogen from binding there to
cause gynocomastia -although it is not nearly as effective as
nolvadex. It can also stimulate the HPTA
(Hypothalamic-Pituitary-Testicular-Axis), and stimulates LH (Luteinizing
Hormone) and FSH (Follicle Stimulating Hormone). LH and FSH
stimulate the release of testosterone. Unfortunately, Clomid
does this only weakly, and there are much better ancillary
products on the market. It works, but I think Nolvadex is much
better.
Final Grade:
C-
Buy research clomid
Nolvadex
Nolvadex is a Selective Estrogen Receptor Modulator. This
means that it acts on the Estrogen receptor (called the "ER"
but having nothing to do with George Clooney or Anthony
Edwards). Now, this also means that it acts as an estrogen in
some tissues which acts as an anti-estrogen in some tissues.
The estrogen receptor's ligand binding domain is just of a
number of amino acid sequences "folded" into a series of
helixes, which have the ability to change conformation.
Different stimuli (such as
Nolvadex) are well documented to
have the ability to change the conformation of a very
important helix (helix 12, for those keeping score at home).
When estradiol binds the ER, this particular helix takes on a
conformation that allows DNA transcription to mRNA, and
estrogenic effects are then expressed in the body. When
Nolvadex (Tamoxifen) binds to it, the antagonist changes the
shape of this helix in such a way that it now folds (or bends)
in such a way to prevent proper binding of estrogen, and
subsequent transcription of DNA to mRNA.
Sadly, if you take progesteronic (I made that word up)
steroids and use nolvadex, you may be at an increased risk for
progesteronic sides, as nolvadex may increase progesterone
receptors (Gynecol Oncol. 1999 Mar;72(3):331-6). So
besides competing with estrogen at the receptor, these drugs
both increase serum test levels, and both drugs may also alter
blood lipid profiles. With regards to Clomid and Nolvadex,
I’ve found some research that indicates that 20mgs of
tamoxifen is equal to 150mgs of clomid for purposes of
testosterone elevation, FSH and LH, but tamoxifen did not
decrease the LH response to LHRH (Fertil Steril. 1978
Mar;29(3):320-7). Interestingly, Nolvadex can even be used
in small doses just as effectively as larger doses, when it
comes to sperm indices and spermatogenesis. (“Effect
of lower versus higher doses of
tamoxifen on pituitary-gonadal function and sperm indices
in oligozoospermic men”. Dony JM, Smals AG, Rolland R, Fauser
BC,
Thomas CM.)
So in
this case, we can actually use much lower doses than the
egregiously recommended 40-60mgs/day. 5mgs a day seems to be
as effective as 20, with regards to basal or LHRH stimulated
gonadotropin and testosterone response or the E2/T ratio
(Ibid).
So that makes
Nolvadex great for preventing gyno, and superb
for Post Cycle Therapy even at lower dosages, but not my
favorite Ancillary product during a cycle, unless I need to
help my lipid profile or just prevent gyno. I give nolvadex a
…
Final Grade:
B-
Buy research Nolvadex
Aromasin
Aromasin basically is an aromatase inactivator...It actually
makes estrogen receptors useless in a sense, because it
inhibits the aromatase enzyme from creating more estrogen.
This is like having a wall socket but no radio to plug into
it…kind of useless, right? Instead of just inhibiting
production (as a Type-II anti-aromatase would do) it
irreversibly cuts off estrogen production from the enzyme it
attaches to.
Aromasin can also cause androgenic sides, so it’s
not ideal for women, however. It’s not particularly harsh on
cholesterol, and can be effectively used with Nolvadex. I’ve
seen studies indicating that it reduces estrogen in your body
by about 80%, possibly making it too strong, for maximum gains
and staying healthy on a long (12 weeks or more) cycle. Aromasin,
at 20mgs/day, will raise your testosterone levels by about
60%, and will even help out your free to bound testosterone
ratio by lowering your body’s levels of Sex Hormone Binding
Globulin (SHBG), by roughly 20% (The
Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12
5951-5956)…It’s
perfect for use in PCT, for many other reasons (it interacts
more favorably with Nolvadex than other AIs). But it’s not
100% what we want during a cycle…for this reason, I give it a
strong…
Final Grade:
B+
Buy research Aromasin
LiquiDex
From the research I've done, this seems to be the best
ancillary compound around for use on a cycle. First off, 1mg
per day of this stuff (J Clin Endocrinol Metab 2000
Jul;85(7):2370-7 ) was shown to decrease estrogen by about
50% and increase testosterone levels by 58%. That’s a level of
estrogen suppression I’m very comfortable with on virtually
any cycle. Interestingly, that same study showed that those
results were had with .5mgs/day as well. So, since you can
elevate testosterone, lower estrogen (but not excessively),
and keep healthy joints and lipids, and do this at a half mg
per day, I give this my highest rating for an ancillary
product to use on a cycle…
Final Grade:
A
Buy research Liquidex
Letrozole
Letrozole is another type II (competitive) AI. Letrozole is
actually a lot more effective than Arimidex in its ability to
pass thru the cell membrane of lipid (fat) cells as well as
inhibit the activity of aromatase. In some studies,
circulating estrogen levels are totally undetectable in most
patients taking Letrozole, and just like Arimidex, it has even
been used in specific cases to increase testosterone to normal
levels (from sub-normal ones) and increase LH, and FSH (Epilepsy
Behav. 2004 Apr;5(2):260-3). Unfortunately, it does this
too well, and although it cleared up my minor gyno lumps, and
has been shown to do this in animal studies as well (J
Steroid Biochem Mol Biol. 2001 Dec;79(1-5):27-34. Aromatase
overexpression transgenic mice model: cell type specific
expression and use of
letrozole
to abrogate mammary hyperplasia without affecting normal
physiology.). This got my gyno lumps to the point that
they are totally gone now, prolonged use lowered my immune
system and gave me joint problems (due to a lack of estrogen).
It’s very strong, and maximum inhibition of aromatase in one
study was found to happen in women at tiny 100mcg doses (J
Clin Endocrinol Metab. 1995 Sep;80(9):2658-60.)If
you aren’t on a cutting cycle, training for a contest, or
trying to clear up some gyno,
Letrozole is not for you. Still,
it’s the most potent Aromatase Inhibitor on the market today,
so I’ll cautiously give it a …
Final Grade:
B
Buy research Letrozole
So, in
summary, I believe Liquidex (Liquidex or Anastrozole) to be
the best ancillary product for use on most of the cycles that
I see posted on the internet, or talked about in my gym.
