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Old 07-13-2008, 06:22 PM   #1
 
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Default Clomid, Nolvadex and Testosterone Stimulation

Originally from Mind and Muscle.

Clomid, Nolvadex and Testosterone Stimulation
by William Llewellyn



Introduction


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.

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.



Pituitary Sensitivity to GnRH


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.

In next month's follow-up article I will be discussing the role anti-estrogens play in post-cycle testosterone recovery. Most specifically, I will be detailing what a proper post-cycle ancillary drug program looks like, and explain why anti-estrogens alone are not effective during this window of time.


References:

1. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7

2. Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro. Adashi EY, Hsueh AJ, Bambino TH, Yen SS. Am J Physiol 1981 Feb;240(2):E125-30

3. The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men. Adamopoulos, Kapolla et al. Int J Androl 4 (1981) 639-45
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Old 07-14-2008, 04:43 PM   #2
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Bill makes some valid points and he has done his homework but some of his recommendations are dated in regard to what we now know about Nolva and its ability to suppress IGF-1. While it can be used as Bill describes, I would ask why anyone would choose this as an option. Clomid, and AI, and HCG will work equally well (actually better from my observations) and none of those compounds present the user with the potential for suppression of IGF-1 or hepatoxicity as Nolva does.

I am not saying Bill's protocol is wrong. There was a time in the late 90's I recommend that Nolva be used as the BASE of every PCT protocol. However, today's research affords us a better understanding of the HPTA and its workings with drugs like Nolva. What we know now should serve as our guide; not what we (incorrectly) understood 10 years ago.
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Old 07-14-2008, 04:56 PM   #3
 
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Quote:
Originally Posted by DR_C View Post
Bill makes some valid points and he has done his homework but some of his recommendations are dated in regard to what we now know about Nolva and its ability to suppress IGF-1. While it can be used as Bill describes, I would ask why anyone would choose this as an option. Clomid, and AI, and HCG will work equally well (actually better from my observations) and none of those compounds present the user with the potential for suppression of IGF-1 or hepatoxicity as Nolva does.

I am not saying Bill's protocol is wrong. There was a time in the late 90's I recommend that Nolva be used as the BASE of every PCT protocol. However, today's research affords us a better understanding of the HPTA and its workings with drugs like Nolva. What we know now should serve as our guide; not what we (incorrectly) understood 10 years ago.
Thanks for your input I am not sure how old the post was but none the less a good source of info
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Old 07-14-2008, 09:22 PM   #4
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Quote:
Originally Posted by LLLLern View Post
Thanks for your input I am not sure how old the post was but none the less a good source of info
Agreed - good information. My guess would be the copy edit date is somewhere around 2003 - that's about the time Bill started to follow the work of Mike Scally and subscribe to his PoWer Protocol.

Regards,
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Old 07-15-2008, 02:19 PM   #5
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Is Nolva sufficient enough for PCT after a cycle of PHs such as 1-AD/4AD, or would a test booster be needed in addition to it?
Old 07-15-2008, 06:55 PM   #6
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Quote:
Originally Posted by LBVT View Post
Is Nolva sufficient enough for PCT after a cycle of PHs such as 1-AD/4AD, or would a test booster be needed in addition to it?
Run an AI in inverse to the SERM (SERM decreasing of the weeks and AI increasing over the weeks). Of course nolva is not my choice for any PCT for the issue already discussed.

Regards,
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Old 07-15-2008, 07:11 PM   #7
 
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Quote:
Originally Posted by DR_C View Post
Run an AI in inverse to the SERM (SERM decreasing of the weeks and AI increasing over the weeks). Of course nolva is not my choice for any PCT for the issue already discussed.

Regards,

I ran mine like so

40 30 20 20 10 nolv
00 00 25 50 50 25 25ATD

that worked well for me after a Mdrol and Trenadrol cycle
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Old 07-20-2008, 05:05 PM   #8
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Quote:
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Run an AI in inverse to the SERM (SERM decreasing of the weeks and AI increasing over the weeks). Of course nolva is not my choice for any PCT for the issue already discussed.

Regards,
yea tamox is really not ideal for men....
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Quote:
Originally Posted by LLLLern View Post
Thanks for your input I am not sure how old the post was but none the less a good source of info
Please don't post articles for the sake of posting articles, especially when they suck and this one does in fact suck...hes basically saying pick nolva over clomid because its cheaper...

When you decide to venture into the land of AAS and have first hand experience then you may comment, until then, don't walk into territory you don't understand.
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Old 07-20-2008, 05:55 PM   #10
 
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