I have received a lot of heat lately about my preference for Nolvadex
over Clomid, which I hold for all purposes of use (in the bodybuilding
world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting
drug, and as a testosterone-stimulating compound. Most people use Nolvadex
to combat gynecomastia over Clomid anyway, so that is an easy sell.
And for cholesterol, well, most bodybuilders unfortunately pay little
attention to this important issue, so by way of disinterest, another
easy opinion to discuss. But when it comes to using Nolvadex for increasing
endogenous testosterone release, bodybuilders just do not want to hear
it. They only seem to want Clomid. I can only guess that this is based
on a long rooted misunderstanding of the actions of the two drugs. In
this article I would therefore like to discuss the specifics for these
two agents, and explain clearly the usefulness of Nolvadex for the specific
purpose of increasing testosterone production.
Clomid and Nolvadex
I am not sure how Clomid and Nolvadex became so separated in the minds
of bodybuilders. They certainly should not be. Clomid and Nolvadex are
both anti-estrogens belonging to the same group of triphenylethylene
compounds. They are structurally related and specifically classified
as selective estrogen receptor modulators (SERMs) with mixed agonistic
and antagonistic properties. This means that in certain tissues they
can block the effects of estrogen, by altering the binding capacity
of the receptor, while in others they can act as actual estrogens, activating
the receptor. In men, both of these drugs act as anti-estrogens in their
capacity to oppose the negative feedback of estrogens on the hypothalamus
and stimulate the heightened release of GnRH (Gonadotropin Releasing
Hormone). LH output by the pituitary will be increased as a result,
which in turn can increase the level of testosterone by the testes.
Both drugs do this, but for some reason bodybuilders persist in thinking
that Clomid is the only drug good at stimulating testosterone. What
you will find with a little investigation however is that not only is
Nolvadex useful for the same purpose, it should actually be the preferred
agent of the two.
Pituitary Sensitivity to GnRH
Studies conducted in the late 1970's at the University of Ghent in Belgium
make clear the advantages of using Nolvadex instead of Clomid for increasing
testosterone levels (1). Here, researchers looked the effects of Nolvadex
and Clomid on the endocrine profiles of normal men, as well as those
suffering from low sperm counts (oligospermia). For our purposes, the
results of these drugs on hormonally normal men are obviously the most
relevant. What was found, just in the early parts of the study, was
quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily,
increased serum testosterone levels to 142% of baseline, which was on
par with the effect of 150mg of Clomid daily for the same duration (the
testosterone increase was slightly, but not significantly, better for
Clomid). We must remember though that this is the effect of three 50mg
tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex
typically very similar, we are already seeing a cost vs. results discrepancy
forming that strongly favors the Nolvadex side.
But something more interesting is happening. Researchers were also
conducting GnRH stimulation tests before and after various points of
treatment with Nolvadex and Clomid, and the two drugs had markedly different
results. These tests involved infusing patients with 100mcg of GnRH
and measuring the output of pituitary LH in response. The focus of this
test is to see how sensitive the pituitary is to Gonadotropin Releasing
Hormone. The more sensitive the pituitary, the more LH will be released.
The tests showed that after ten days of treatment with Nolvadex, pituitary
sensitivity to GnRH increased slightly compared to pre-treated values.
This is contrast to 10 days of treatment with 150mg Clomid, which was
shown to consistently DECREASE pituitary sensitivity to GnRH (more LH
was released before treatment). As the study with Nolvadex progresses
to 6 weeks, pituitary sensitivity to GnRH was significantly higher than
pre-treated or 10-day levels. At this point the same 20mg dosage was
also raising testosterone and LH levels to an average of 183% and 172%
of base values, respectively, which again is measurably higher than
what was noted 10 days into therapy. Within 10 days of treatment Clomid
is already exerting an effect that is causing the pituitary to become
slightly desensitized to GnRH, while prolonged use of Nolvadex serves
only to increase pituitary sensitivity to this hormone. That is not
to say Clomid won't increase testosterone if taken for the same 6 week
time period. Quite the opposite is true. But we are, however, noticing
an advantage in Nolvadex.
The Estrogen Clomid
The above discrepancies are likely explained by differences in the estrogenic
nature of the two compounds. The researchers' clearly support this theory
when commenting in their paper, "The difference in response might
be attributable to the weak intrinsic estrogenic effect of Clomid, which
in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding
globulin [SHBG] levels; this increase was not observed after tamoxifen
treatment". In reviewing other theories later in the paper, such
as interference by increased androgen or estrogen levels, they persist
in noting that increases in these hormones were similar with both drug
treatments, and state that," …a role of the intrinsic estrogenic
activity of Clomid which is practically absent in Tamoxifen seems the
most probable explanation".
Although these two are related anti-estrogens, they appear to act very
differently at different sites of action. Nolvadex seems to be strongly
anti-estrogenic at both the hypothalamus and pituitary, which is in
contrast to Clomid, which although a strong anti-estrogen at the hypothalamus,
seems to exhibit weak estrogenic activity at the pituitary. To find
further support for this we can look at an in-vitro animal study published
in the American Journal of Physiology in February 1981 (2). This paper
looks at the effects of Clomid and Nolvadex on the GnRH stimulated release
of LH from cultured rat pituitary cells. In this paper, it was noted
that incubating cells with Clomid had a direct estrogenic effect on
cultured pituitary cell sensitivity, exerting a weaker but still significant
effect compared to estradiol. Nolvadex on the other hand did not have
any significant effect on LH response. Furthermore it mildly blocked
the effects of estrogen when both were incubated in the same culture.
Conclusion
To summarize the above research succinctly, Nolvadex is the more purely
anti-estrogenic of the two drugs, at least where the HPTA (Hypothalamic-Pituitary-Testicular
Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder
certain advantages over Clomid. This is especially true at times when
we are looking to restore a balanced HPTA, and would not want to desensitize
the pituitary to GnRH. This could perhaps slow recovery to some extent,
as the pituitary would require higher amounts of hypothalamic GnRH in
the presence of Clomid in order to get the same level of LH stimulation.
Nolvadex also seems preferred from long-term use, for those who find
anti-estrogens effective enough at raising testosterone levels to warrant
using as anabolics. Here Nolvadex would seem to provide a better and
more stable increase in testosterone levels, and likely will offer a
similar or greater effect than Clomid for considerably less money. The
potential rise in SHBG levels with Clomid, supported by other research
(3), is also cause for concern, as this might work to allow for comparably
less free active testosterone compared to Nolvadex as well. Ultimately
both drugs are effective anti-estrogens for the prevention of gyno and
elevation of endogenous testosterone, however the above research provides
enough evidence for me to choose Nolvadex every time.
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