Nolvadex VS Clomid

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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