Nolva vs. Clomid

Another article I had stored in my favorites that I found helpful.

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

__________________

Good read Scrilla. Thanks!

On a side note, I like Clomid more, because it makes me cry like a girl during PMS.

__________________
Madmaniac is a spiteful, hatefilled person and despises all of you. If he ever meets any of you, he will gouge out your eyes and skull fuck your brain!


MOD@

And who doesn't enjoy a good girly cry once ina while?

__________________

Good read! Thanks scrilla.

__________________
"I came to realize that life lived to help others is the only one that matters and that it is my duty...This is my highest and best use as a human."
-Ben Stein

Nice read, thanks

I have read recently about toremifiene instead of Nolva.

Taken from BB.com Posted by Krzna.

Any thoughts on the issue?

**************************************

As much as this drug is loved for PCT, I think its high time we slowly ease out old school and switch to fareston/toremifene.


MANY THANKS TO JMF :

Here is a good reason why:

Nolvadex is the trade name of a drug containing a molecule called Tamoxifen. Its primary use by male bodybuilders is to prevent gynecomastia (the growth of the breast tissue). It was introduced by steroid guru Dan Duchaine 25 years ago. After a quarter of century, it is time for an update about its use. What I am going to demonstrate is it is high time to eliminate Nolvadex from the bodybuilder's drug stacks.

A Little Bit of History

Back in the late 70's, more and more bodybuilders developed strange lumps around their mammary glands. At first, no one really took notice but more and more competitors grew a gynecomastia. In 1981, the M Olympia had a pretty serious gyno. This was shortly after the introduction of this new drug by Dan Duchaine. At the time, it was a pretty good idea as no one else could came up with a solution in order to prevent this growing problem. Nolvadex was popularised by Dan's first Underground Steroid Handbook. Dan even states that "this drug has a lot of potential but hasn't been used enough yet to find it". After more than 25 years of intensive usage, it is my opinion that it is time to forget about Nolvadex. Why? First, because newer and more effective drugs have been developed. Second, because it seems obvious that Nolvadex impairs muscle growth.

Nolvadex and Muscle Growth

After so many years of usage, it seems pretty clear that if Tamoxifen helps prevent the growth of the nipples, it also weakens the anabolic properties of steroids in a majority of bodybuilders. We are frequently said that this weakening effect is due to the anti-estrogenic action of Nolvadex. According to the fantasy, muscles require both testosterone and estrogens to grow at an optimal rate.

This belief is derived from the results of studies showing that without estrogens, testosterone alone possesses minimal anabolic properties. By increasing the density of androgen receptors, estrogens render the muscles much more sensitive to testosterone (1). This has been demonstrated in a very specific muscle called the levator ani. But this muscle does not reflect what happens in the muscles bodybuilders are interested in (2). Estrogens have even been shown to reduce muscle fiber size (3-4). I think this effect of estrogens is closer to what we experience on bodybuilders.

Another popular explanation of the weakening action of Nolvadex is provided by studies which have shown that it reduced the plasma level of IGF-1. I do not think this is a primary explanation.

What Nolvadex Truly Is

Most lifters assume Nolvadex is a pure estrogen antagonist (which would mean it prevents estrogens from acting on their receptors). As far as bodybuilding is concerned, this assumption is very wrong as Nolvadex is both an estrogen receptor agonist and an antagonist. It all depends upon the tissues. Along with the nipples, on which Nolvadex acts mainly as an antagonist, we are also interested by its behaviour on skeletal muscles, on the liver and on the fat cells.

Nolvadex has been shown to behave as estrogens in skeletal muscles (5). This is a very good thing for every athletes except bodybuilders. You see, estrogens protect muscle cells from the training-induced damages (5-6). It means that one can train more without damaging his muscles. Recovery will also be much faster. But for bodybuilders, the training-induced damages are a key ingredient to trigger growth. Nolvadex will therefore reduce the muscle building effects of resistance training.

As for the impact of Tamoxifen on IGF-1, it simply demonstrates another estrogen-like action of Nolvadex. By rendering the liver less sensitive to growth hormone (probably by reducing the liver density of GH receptors), estrogens and tamoxifen diminish the production of IGF-1. This action of estrogens explains why women produce less IGF-1 than men eventhough the have a higher GH level.

Nolvadex and Muscle Definition

Within 24 to 48 hours, Nolvadex is able to greatly increase muscular definition. As a result, bodybuilders assume Nolvadex will help them reduce their bodyfat level. But this rapid cutting action of Nolvadex is due to an anti-estrogenic action on water retention. Estrogens will make you hold water. Nolvadex will produce the opposite effect. But it says nothing about the impact of Tamoxifen on bodyfat. Depending upon your own production of estrogens and your estrogen receptor density on adipocytes, Nolvadex can act as an antagonist (which would help you lose fat) or an agonist. In that case, Nolvadex will make you fatter especially in the lower body area.

Conclusion: if the introduction of Nolvadex 25 years ago was a brilliant idea, times have changed. Very effective anti-aromatase drugs (such as Letrozole or Anastrazole) have been introduced. They will fight gynecomastia, help prevent the anti-anabolic actions of estrogens, fight fat and water retention. They will also boost natural testosterone production far more effectively than Nolvadex. So, it is up to you to decide whether you wish impair your rate of progression with an outdated drug or move on to the 21st century.

Bibliography:

(1) Max SR. Androgen-estrogen synergy in rat levator ani muscle: glucose-6-phosphate dehydrogenase. Mol Cell Endocrinol. 1984 Dec;38(2-3):103-7.

(2) Rance NE, Max SR. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids. Endocrinology. 1984 Sep;115(3):862-6.

(3) Kobori M, Yamamuro T. Effects of gonadectomy and estrogen administration on rat skeletal muscle. Clin Orthop Relat Res. 1989 Jun;(243):306-11.

(4) Suzuki S, Yamamuro T. Long-term effects of estrogen on rat skeletal muscle. Exp Neurol. 1985 Feb;87(2):291-9.

(5) Koot RW, Amelink GJ, Blankenstein MA, Bar PR. Tamoxifen and oestrogen both protect the rat muscle against physiological damage. J Steroid Biochem Mol Biol. 1991;40(4-6):689-95.

(6) Naessens G, De Slypere JP, Dijs H, Driessens M. Hypogonadism as a cause of recurrent muscle injury in a high level soccer player. A case report. Int J Sports Med. 1995 Aug;16(6):413-7.





Some inferences:
a) Nolvadex effect on estrogen is VERY site specific, and not general. While being a good breast site ERM its effect on skeletal tissue seems way out.
b) While being extremely suppressive on IGF on site, nolva also becomes problematic to use if one runs IGF exogeniously in the PCT.


In support of Ralox:


SERMS are "designer" estrogen-related medications that activate the estrogen receptors, but have different effects on different tissues. There are two kinds of estrogen receptors, and after binding to receptors, the drug-receptor complex can have various conformations. Some of these will act like estrogen, others will inhibit the actions of estrogen.

Advantages of Raloxifene:
Many screening studies of related compounds have been done to search for those which act like estrogen in the desireable ways (stablize bone mass, improve lipid profile) but do not act like estrogen in undesireable ways (cause breast cancer, stimulate the endometrium). The effects on the cardiovascular system are still uncertain: when Ralox was first developed it was felt that estrogen had a beneficial action on the heart, now this is doubted and debated.

Effects on bone physiology
# Decreased bone formation and resorption
# No significant change in bone volume
# Slight increase in mineralization density
# No evidence of osteomalacia or bone toxicity

Another effect of Ralox is that users had fewer asthma attacks and less severe asthma symptoms, strongly suggesting that perhaps estrogen affects airway smooth muscle function by preventing the hyperresponsiveness characteristic of asthma and other chronic lung diseases.

Toxicology report that estrogen, as well as selective estrogen receptor modifiers (SERMs), completely abolished abnormal tracheal constriction in a carbachol test.Carbachol is often used to stimulate, or mimic, contractions of airway and other muscles.

Estrogen has a wide range of actions in the nervous system, including neuroprotection and potentiation of nerve regeneration (Toran-Allerand, 1999; Tanzer et al., 1999; McEwen et al., 2001; Islamov et al., 2002). In spite of the beneficial actions of estrogen on the nervous system, the opportunities for its wide therapeutic application are severely limited because of its adverse side effects in reproductive organs. Therefore, a search for pharmacological substances with selective estrogenic action on the nervous system is of great practical significance.

Other positive effects:
The HDL cholesterol level is considered a strong inverse predictor of cardiovascular disease .Therefore, the absence of an increase in serum HDL cholesterol levels raises concern that raloxifene may not be as effective as estrogen replacement in preventing cardiovascular disease. Although the findings of animal studies are difficult to generalize to humans, recent animal data have also raised concerns that raloxifene may not prevent the progression of coronary artery disease. Because no long-term trials have been conducted, it is impossible to determine whether the small lipid effects produced by raloxifene correlate with a smaller degree of cardioprotective activity.

Raloxifene vs Tamox
From the above we can infer that Ralox maybe a better choice over Tamox as it lends the following positive effects on use.
a)Increasing bone density
b)Prevention of asthma
c)Nerve regeneration and neuroprotection
d)No changes in serum concentrations of high-density lipoprotein (HDL) cholesterol and triglycerides, while reducing LDL levels.


It would be nice if others can contribute to this thread with alternatives.

A lot of people switchin to toremefine, now. And I've heard nothing, but good things. A few people have commented that Nolva still works better for gyno. I'm not sure if I buy th whole 'nolva impairs muscle growth' thing, though, as for years people have used it without any major issues in that regard. But if toremefine proves to be as good as it looks, then hell, I'm sure it'll be the new standard. Good to see you're doing your research tho.

__________________

Cool. Seems it'll come down to which is cheaper then. Either way it'll be w/ clomid, so I guess it doesn't matter too much.

I like a Tormafine/aromasin PCT

never used Clomid.I might try it as well as clomid next PCT and throw in some Hcg


Kartel

__________________
VET at a few,VIP at couple prolly Elite somewhere else.

Integrity and loyalty are the foundation of my character.
Tired does not mean weak,injured does not mean weak,only WEAK means WEAK
-"Persaverance is not a long race,but many short ones right after another."-Walter Elliot-

Where do you get the tormafine from? Ive look evvverywhere, I heard that tormafine was a lot better then nolva. Isnt and AI bad for PCT? I thought you didnt want to lower you estrogen to much, but I did see this article thought that said armidex used alone increases natural next through lowering your estogen, so im guessing that has to do with the feedback loop?

I was just reading this but I think it is false, ive heard many times arimidex LOWERS estogen and nolvadex binds to the estrogen receptor..

http://www.muscletalk.co.uk/m_1885063/mpage_3/tm.htm

__________________
"I came to realize that life lived to help others is the only one that matters and that it is my duty...This is my highest and best use as a human."
-Ben Stein